1037-00005 · Solstice Biomedical Devices Ltd · Prosecution Documents/CON-2

draft-declaration-connolly-rule-132.docx DOCUMENT Litigation

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DRAFT — PRIVILEGED & CONFIDENTIAL — FOR CLIENT REVIEW Prepared by: Peter Vassiliev (Reg. No. 72,340) and Dr. Claire Nakamura (Reg. No. 66,203) Calderwood & Harkness LLP

IN THE UNITED STATES PATENT AND TRADEMARK OFFICE

DECLARATION OF DR. AISLING CONNOLLY UNDER 37 C.F.R. § 1.132

I. Introduction and Identity of Declarant

1. My name is Dr. Aisling Connolly. I am a citizen of Ireland. I am currently employed as Vice President of Research & Development at Solstice Biomedical Devices Ltd. ("Solstice" or "SBD"), with offices located at Unit 4, Liffey Innovation Campus, Parkgate Street, Dublin 8, D08 XR29, Ireland. I am over eighteen (18) years of age and am competent to make this declaration. The facts set forth herein are based on my personal knowledge, my review of the relevant patent documents, and my professional experience in the field of cardiac cryoablation and electrophysiology mapping technologies. If called upon to testify, I could and would testify competently to the matters stated herein.

2. I make this declaration under 37 C.F.R. § 1.132 in support of the patentability of the claims currently pending in U.S. Patent Application No. 17/851,216, entitled "Cryoablation Catheter with Integrated Impedance Mapping Electrodes" (hereinafter, the "'216 Application" or "CON-2"). This declaration is submitted in connection with the Applicant's response to the Non-Final Office Action mailed by the United States Patent and Trademark Office ("USPTO") on September 15, 2024.

3. I am a named co-inventor on all four applications in the CryoNova patent family, which consists of the following related applications and patents:

(a) U.S. Patent Application No. 16/914,337, filed June 28, 2021, now issued as U.S. Patent No. 11,284,561 (the "parent application" or the "'561 Patent");

(b) U.S. Patent Application No. 17/702,489 ("CON-1"), a continuation of the parent application;

(c) U.S. Patent Application No. 17/851,216 ("CON-2"), the application at issue in this declaration, also a continuation of the parent application; and

(d) U.S. Patent Application No. 18/109,744 ("CON-3"), likewise a continuation of the parent application.

4. The co-inventors on the CryoNova patent family are as follows:

(a) Dr. Tomás Brennan, Chief Medical Officer and Co-Founder of Solstice Biomedical Devices Ltd., is a named co-inventor on all four applications in the CryoNova patent family (i.e., the parent application, CON-1, CON-2, and CON-3).

(b) Dr. Henrik Paulsen, formerly a Senior Engineer at Solstice Biomedical Devices Ltd. and currently employed at Arclight Therapeutics GmbH, is a named co-inventor on the parent application (U.S. 16/914,337, now U.S. Patent No. 11,284,561) and on CON-1 (U.S. 17/702,489) only. Dr. Paulsen is not a named co-inventor on CON-2 or CON-3.

5. The assignee of the '216 Application and all other applications in the CryoNova patent family is Solstice Biomedical Devices Ltd., an Irish private limited company registered with the Companies Registration Office of Ireland under CRO No. 647832.

II. Qualifications and Technical Background of Declarant

6. I hold a Ph.D. in Biomedical Engineering from Trinity College Dublin, which I received in 2009. My doctoral research focused on the thermal modeling of cryogenic tissue ablation and the design of cryoprobe tip geometries for cardiac applications. A copy of my full curriculum vitae is attached hereto as Exhibit A.

7. I have over fifteen (15) years of experience in medical device research and development, with a particular specialization in cardiac cryoablation catheter design and electrophysiology mapping technologies. Throughout my career, I have been involved in the design, prototyping, pre-clinical testing, and clinical evaluation of catheter-based systems for the treatment of cardiac arrhythmias, including atrial fibrillation, atrial flutter, and ventricular tachycardia.

8. In my current role as Vice President of Research & Development at Solstice Biomedical Devices Ltd., I lead the engineering team responsible for the design, development, and testing of the CryoNova cryoablation catheter system. This team currently comprises twenty-three (23) engineers and scientists across the disciplines of mechanical engineering, electrical engineering, software engineering, and biomedical engineering. I have held this position since 2018, when I joined Solstice as one of the company's earliest technical hires.

9. I personally led the development of the variable-zone cooling architecture and the integrated impedance mapping electrode array that are the subject of the claims pending in the '216 Application. In this capacity, I was responsible for the initial concept definition, the iterative engineering design process, the bench testing and verification protocols, and the coordination with external regulatory and clinical affairs consultants in preparation for clinical evaluation.

10. I am familiar with the current state of the art in cryoablation catheter technology as it pertains to pulmonary vein isolation for the treatment of atrial fibrillation. This familiarity extends to competing commercial products and patent portfolios, including those of Vantage Cryosurgical Systems, Inc. ("Vantage"), Cascade Holdings, Greaves Corporation, and others. I have reviewed published clinical literature, issued patents, and patent application publications relating to cryoablation balloon catheter design, impedance-based tissue characterization, and electrophysiology mapping catheters.

11. In addition to my design and development responsibilities, I served as the engineering and technical lead during the European first-in-human clinical study of the CryoNova system. That study enrolled fifteen (15) patients at two investigational sites in Ireland and the Netherlands and was conducted under European regulatory authorization. I subsequently served as the technical lead during the United States pivotal Investigational Device Exemption ("IDE") trial of the CryoNova system, designated as the FROST-AF trial (IDE No. G210047), which enrolled two hundred and twenty (220) patients at fourteen (14) investigational sites across the United States.

12. In preparation for this declaration, I have reviewed the following documents:

(a) The Non-Final Office Action mailed September 15, 2024, in connection with U.S. Patent Application No. 17/851,216;

(b) The pending claims (Claims 1–20) of U.S. Patent Application No. 17/851,216, as filed;

(c) U.S. Patent No. 10,537,418, assigned to Vantage Cryosurgical Systems, Inc. (hereinafter, the "Vantage '418 patent" or "'418 patent");

(d) U.S. Patent No. 9,861,432, assigned to Vantage Cryosurgical Systems, Inc. (hereinafter, the "Vantage '432 patent" or "'432 patent");

(e) U.S. Patent Application Publication No. 2019/0183567, assigned to Helios Surgical Technologies, Inc. (hereinafter, the "Helios '567 publication" or "'567 publication");

(f) U.S. Patent No. 11,284,561, the parent patent in the CryoNova family (hereinafter, the "'561 Patent"); and

(g) The complete specification and prosecution history of U.S. Patent Application No. 17/851,216.

III. Purpose of Declaration

13. The purpose of this declaration is to provide the Examiner with factual evidence and technical context regarding the following matters:

(A) The distinctions between the claimed CryoNova cryoablation catheter system with integrated impedance mapping electrodes and the prior-art references cited in the Non-Final Office Action mailed September 15, 2024; and

(B) The full written-description support in the parent specification (U.S. Patent No. 11,284,561) for the impedance mapping calibration algorithm recited in Claims 9–14 of the '216 Application.

14. Specifically, this declaration addresses the following rejections and objections set forth in the Non-Final Office Action:

(i) Claims 1–8 — rejected under 35 U.S.C. § 103 as allegedly obvious over U.S. Patent No. 10,537,418 ("Vantage '418") in view of U.S. Patent No. 9,861,432 ("Vantage '432") and U.S. Publication No. 2019/0183567 ("Helios '567");

(ii) Claims 9–14 — rejected under 35 U.S.C. § 112(a) for alleged lack of written description regarding the impedance mapping calibration algorithm recited in those claims; and

(iii) Claims 15–20 — objected to as depending from a rejected base claim, but indicated by the Examiner as containing allowable subject matter.

15. I respectfully submit this declaration to assist the Examiner in evaluating the technical merits of the pending claims and to provide the perspective of a named co-inventor who personally conceived and developed the technology at issue.

IV. Overview of the CryoNova Technology

16. The CryoNova cryoablation catheter system is a second-generation cryoablation catheter designed for pulmonary vein isolation ("PVI") in the treatment of atrial fibrillation. Atrial fibrillation is the most common sustained cardiac arrhythmia, affecting millions of patients worldwide, and catheter-based ablation of the pulmonary veins has become an established treatment strategy for drug-refractory cases. The CryoNova system was developed at Solstice Biomedical Devices Ltd. to address specific clinical and technical limitations observed with existing single-zone cryoablation balloon catheters.

17. The first key differentiating feature of the CryoNova system is its variable-zone cooling architecture. Unlike conventional single-zone balloon catheters — which apply a uniform circumferential cryoablation energy across the entire contact surface — the CryoNova catheter incorporates multiple discrete cooling zones that can be independently activated, deactivated, or modulated. This variable-zone architecture enables the physician to selectively cryoablate specific tissue segments around the pulmonary vein ostium, concentrating ablation energy on areas requiring treatment while sparing areas where ablation is unnecessary or where critical anatomical structures (such as the phrenic nerve or esophagus) are at risk of collateral injury.

18. The second key differentiating feature of the CryoNova system is its integrated impedance mapping electrodes. These electrodes are embedded directly within the catheter body, positioned adjacent to and co-located with the discrete cooling zones. The integrated electrodes allow real-time tissue impedance measurements to be taken during the cryoablation procedure itself, enabling the physician to monitor lesion formation progress and assess tissue contact quality in real time, without requiring the insertion or manipulation of a separate diagnostic mapping catheter. This integration eliminates the need for catheter exchanges during the procedure, reduces procedural complexity, and provides impedance data that is spatially registered to the ablation zones.

19. The third key differentiating feature of the CryoNova system is its impedance mapping calibration algorithm. This algorithm processes the impedance data collected by the integrated electrodes and distinguishes between viable myocardial tissue and tissue that has been successfully ablated. The algorithm accounts for the temperature-dependent changes in tissue impedance that occur during cryoablation — a factor that is not present in room-temperature or body-temperature impedance mapping systems. The output of the calibration algorithm is a zone-by-zone tissue characterization map, which is provided to the system's control unit as a feedback loop for adaptive multi-zone cryoablation delivery. In this way, the CryoNova system can automatically adjust the cooling energy delivered to each zone based on real-time tissue characterization, creating a closed-loop ablation system.

20. These three features — variable-zone cooling architecture, integrated impedance mapping electrodes, and the impedance mapping calibration algorithm — are the subject of the claims in the CryoNova patent family. The '216 Application (CON-2) is specifically directed to the catheter structure incorporating the integrated impedance mapping electrodes and their arrangement relative to the variable-zone cooling architecture, as well as the calibration algorithm that enables real-time tissue characterization during cryoablation.

V. Discussion of the Cited Prior Art

21. In this section, I provide my technical analysis of each of the three prior-art references cited in the Non-Final Office Action, based on my review of those references and my familiarity with the field.

V.A. U.S. Patent No. 10,537,418 (Vantage Cryosurgical Systems, Inc.)

22. U.S. Patent No. 10,537,418 (the "Vantage '418 patent") is assigned to Vantage Cryosurgical Systems, Inc., which I understand to be located at 1420 Gateway Boulevard, South San Francisco, California 94080. The Vantage '418 patent describes a cryoablation balloon catheter designed for pulmonary vein isolation.

23. The cryoablation catheter disclosed in the Vantage '418 patent is a single-zone cryoablation balloon catheter. The balloon described in the '418 patent is a compliant balloon that is designed to conform to the anatomical contour of the pulmonary vein ostium upon inflation and to deliver a uniform circumferential cryoablation energy to the tissue in contact with the balloon surface. The entire balloon acts as a single cooling zone — there is no teaching, suggestion, or disclosure in the '418 patent of dividing the balloon into discrete, independently controllable cooling zones.

24. Critically, the Vantage '418 patent does not teach or suggest any form of integrated impedance mapping electrodes within the catheter body. The '418 patent does not describe the use of impedance-based measurements for tissue characterization, lesion assessment, or contact quality monitoring. To the extent that the '418 patent describes any form of tissue or procedural monitoring, such monitoring is limited to temperature sensors (thermocouples) that measure the temperature of the balloon surface or the adjacent tissue during cryoablation. Temperature-based monitoring provides only an indirect and imprecise indicator of lesion formation; it does not provide the impedance-based tissue characterization that is central to the CryoNova system's claims.

25. In my professional opinion, a person of ordinary skill in the art reading the Vantage '418 patent would understand it to be directed to a fundamentally different design approach from the CryoNova system. The '418 patent embodies the conventional single-zone balloon cryoablation paradigm — uniform circumferential cooling applied to the entire pulmonary vein ostium — without any motivation or suggestion to deviate from that paradigm by introducing variable-zone cooling or integrated impedance sensing. The absence of any impedance-related disclosure in the '418 patent is significant: it reflects the fact that the Vantage approach was not conceived as a platform for real-time tissue characterization, and there is nothing in the '418 patent that would lead a skilled artisan toward the integration of impedance mapping electrodes into a cryoablation catheter.

V.B. U.S. Patent No. 9,861,432 (Vantage Cryosurgical Systems, Inc.)

26. U.S. Patent No. 9,861,432 (the "Vantage '432 patent") is also assigned to Vantage Cryosurgical Systems, Inc. The '432 patent describes improvements to cryoablation balloon catheter construction, including innovations in balloon wall materials, refrigerant delivery mechanisms, and methods for enhancing the thermal performance of the balloon during cryoablation.

27. The '432 patent is directed to enhancing the uniformity and efficiency of the single-zone cooling approach described in related Vantage patents, including the '418 patent. The improvements disclosed in the '432 patent — such as multi-layer balloon wall constructions for improved thermal conductivity and modified refrigerant injection patterns for more uniform cooling — are all directed to optimizing the performance of a single, uniform cooling zone. None of these improvements relate to dividing the balloon into multiple independently controllable cooling zones, nor do they relate to any form of impedance-based tissue sensing or characterization.

28. Like the '418 patent, the Vantage '432 patent does not disclose or suggest impedance mapping electrodes integrated into the catheter body. The '432 patent does not address tissue characterization through impedance measurement, does not describe any electrode configuration for that purpose, and does not discuss the challenges associated with impedance measurement in a cryogenic environment.

29. In my professional opinion, combining the teachings of the Vantage '432 patent with those of the Vantage '418 patent would yield, at most, an improved single-zone cryoablation balloon — i.e., a balloon with better materials and more uniform cooling, but still fundamentally a single-zone design without impedance mapping capability. There is no teaching, suggestion, or motivation in either the '418 patent or the '432 patent to incorporate impedance mapping electrodes into the catheter body, and the combination of these two references does not bridge the gap between their disclosures and the claims of the '216 Application.

V.C. U.S. Publication No. 2019/0183567 (Helios Surgical Technologies, Inc.)

30. U.S. Patent Application Publication No. 2019/0183567 (the "Helios '567 publication") is assigned to Helios Surgical Technologies, Inc., which I understand to be located at 750 Bering Drive, Suite 400, Houston, Texas 77057. The Helios '567 publication describes a standalone diagnostic impedance mapping catheter for use in cardiac electrophysiology procedures.

31. The Helios '567 publication teaches the concept of using impedance-based measurements to characterize cardiac tissue. Specifically, the Helios catheter is described as a multi-electrode catheter that is introduced into the cardiac chambers to generate impedance maps of the endocardial surface. These impedance maps can be used by the physician to identify areas of viable tissue, scar tissue, and transitional tissue (such as the border zones of prior ablation lesions).

32. However, the Helios '567 publication describes this impedance mapping functionality exclusively in the context of a separate, standalone diagnostic mapping catheter — not in the context of a cryoablation catheter or any other therapeutic ablation device. The Helios catheter is designed to be used as a diagnostic tool, either before or after an ablation procedure, to assess the cardiac substrate. It is not designed to deliver ablation energy of any kind, and it is not designed to operate simultaneously with an ablation catheter.

33. Importantly, the Helios '567 publication does not teach or suggest integrating impedance mapping electrodes into a cryoablation catheter. Nor does the Helios publication describe or address the specific technical challenges that arise when impedance measurements are performed during active cryoablation. These challenges include, but are not limited to:

(a) Electrode signal degradation at cryogenic temperatures: The electrical properties of electrode materials and electrode-tissue interfaces change significantly at cryogenic temperatures (typically −40°C to −80°C at the balloon surface during cryoablation). These changes can cause baseline shifts, increased noise, and reduced signal fidelity in impedance measurements, effects that are not encountered in the body-temperature environment for which the Helios catheter was designed.

(b) Thermal artifact compensation: During active cryoablation, the tissue impedance changes not only as a function of cellular injury (the parameter of interest for lesion assessment) but also as a direct function of temperature reduction. Separating the temperature-dependent impedance change from the lesion-dependent impedance change requires a specialized calibration algorithm — the very algorithm recited in Claims 9–14 — that is neither described nor suggested in the Helios publication.

(c) Mechanical integration challenges: Incorporating impedance mapping electrodes into the surface of a compliant or semi-compliant cryoablation balloon presents mechanical design challenges that are entirely distinct from the electrode placement considerations in a conventional mapping catheter. These challenges include maintaining electrode contact with tissue during balloon inflation and deflation, routing electrical conductors through the catheter shaft without interfering with refrigerant delivery pathways, and ensuring that the electrodes do not compromise the structural integrity of the balloon wall.

34. In my professional opinion, a person of ordinary skill in the art would not have been motivated to combine the impedance mapping concept of the Helios '567 publication with the single-zone cryoablation balloon concepts of the Vantage '418 and '432 patents. The reasons for this conclusion are threefold:

(i) The physical integration of impedance electrodes into a cryoablation balloon presents distinct engineering challenges that are not addressed, recognized, or contemplated in any of the three cited references. A skilled artisan would have recognized these challenges as substantial obstacles to any such combination.

(ii) The Helios device is explicitly designed to function at body temperature (approximately 37°C), not at the cryogenic temperatures (approximately −40°C to −80°C) encountered during cryoablation. The impedance measurement techniques described in the Helios publication are not validated for, nor adapted to, operation at cryogenic temperatures. A skilled artisan would have understood that simply placing Helios-type electrodes on a Vantage-type balloon would not yield a functional impedance mapping system during active cryoablation without substantial additional inventive work, including the development of a temperature-compensation calibration algorithm.

(iii) There is no suggestion in any of the three cited references that impedance mapping and cryoablation delivery should occur from the same catheter simultaneously. The conventional clinical workflow in the art at the relevant time involved using separate catheters for mapping and ablation — a practice that the CryoNova system was specifically designed to improve upon. The cited references reflect this conventional separation-of-function paradigm and do not suggest departing from it.

VI. Distinctions Between the Claimed Invention and the Prior Art — Claims 1–8 (§ 103 Rejection)

35. Claims 1–8 of the '216 Application recite a cryoablation catheter with integrated impedance mapping electrodes arranged in a specific configuration that enables simultaneous cryoablation delivery and real-time impedance-based tissue characterization. Independent Claim 1, in particular, recites a cryoablation catheter comprising a catheter body, an expandable cryoablation element having a plurality of discrete cooling zones, a plurality of impedance mapping electrodes integrated into the catheter body and positioned adjacent to respective discrete cooling zones, and electrical conductors coupling the impedance mapping electrodes to a control unit. Claims 2–8 depend from Claim 1 and further define the specific arrangement, number, and configuration of the impedance mapping electrodes relative to the cooling zones, as well as structural features of the catheter body that facilitate simultaneous ablation and impedance sensing.

36. Based on my review of the cited references and my understanding of the claimed invention, I respectfully submit that the combination of the Vantage '418 patent, the Vantage '432 patent, and the Helios '567 publication does not render Claims 1–8 obvious. My technical basis for this opinion is as follows:

(1) No reference, alone or in combination, discloses or suggests the structural integration of impedance mapping electrodes within a cryoablation catheter body. As discussed in Section V above, the Vantage '418 and '432 patents do not disclose impedance mapping electrodes of any kind. The Helios '567 publication discloses impedance mapping electrodes, but only in the context of a standalone diagnostic mapping catheter — not integrated into a cryoablation catheter. None of the three references teaches or suggests that impedance mapping electrodes should be incorporated into the physical structure of a cryoablation catheter so as to enable simultaneous ablation and impedance sensing from a single device.

(2) The variable-zone cooling feature of the CryoNova design is not taught or suggested by the uniform single-zone Vantage balloon design. Claims 1–8 recite a cryoablation element having "a plurality of discrete cooling zones." This feature is a foundational structural element of the claimed invention and is directly related to the arrangement of the impedance mapping electrodes, which are positioned "adjacent to respective discrete cooling zones" for zone-by-zone impedance monitoring. The Vantage '418 and '432 patents disclose only a single, uniform cooling zone. A person of ordinary skill in the art reading the Vantage patents would not have been motivated to redesign the single-zone balloon as a multi-zone balloon, because the entire thrust of the Vantage approach is directed to optimizing uniform circumferential cooling.

(3) The specific electrode arrangement claimed in Claims 1–8 has no analog in any of the cited references. Claims 1–8 recite impedance mapping electrodes that are specifically positioned adjacent to discrete cooling zones for zone-by-zone impedance monitoring. This spatial co-registration of electrodes with cooling zones is a structural feature that enables the CryoNova system's unique capability of providing zone-specific tissue characterization data during cryoablation. The Helios publication describes a multi-electrode mapping catheter, but the electrode arrangement in the Helios catheter is designed for general endocardial surface mapping and is not configured for zone-by-zone monitoring in coordination with discrete cooling zones. There is no analog in any of the cited references for the specific electrode-to-cooling-zone spatial relationship recited in the claims.

(4) The technical challenges of impedance measurement at cryogenic temperatures are neither recognized nor addressed in the cited art. As I discussed in paragraphs 33–34 above, performing impedance measurements during active cryoablation introduces technical challenges — including electrode signal degradation at cryogenic temperatures, thermal artifact compensation, and mechanical integration challenges — that are entirely absent from the disclosures of the cited references. A person of ordinary skill in the art would have recognized these challenges as significant barriers to the combination proposed in the Office Action and would not have had a reasonable expectation of success in achieving the claimed integration without the inventive contributions reflected in the '216 Application.

37. In addition to the foregoing technical distinctions, I wish to provide the Examiner with further evidence of the non-obvious character of the claimed invention. The CryoNova system's integration of impedance mapping electrodes into a variable-zone cryoablation catheter was not achieved through routine engineering or straightforward combination of known elements. Rather, the development required extensive engineering iteration over a period of approximately two years (2019–2021), involving multiple prototype iterations, systematic bench testing under simulated cryogenic conditions, and ultimately a first-in-human clinical study in Europe (n=15 patients) to validate the feasibility and functionality of the integrated approach. The challenges encountered during this development process — particularly with respect to maintaining reliable impedance measurements during active cryoablation — confirmed that the integration required inventive effort that went well beyond routine skill in the art. These development challenges are documented in internal Solstice engineering records and could be made available for the Examiner's review if requested.

VII. Written-Description Support for the Impedance Mapping Calibration Algorithm — Claims 9–14 (§ 112(a) Rejection)

38. The Examiner rejected Claims 9–14 under 35 U.S.C. § 112(a) for alleged lack of written description regarding the impedance mapping calibration algorithm recited in those claims. I respectfully submit that the parent specification — i.e., the specification of U.S. Patent No. 11,284,561, from which the '216 Application claims priority as a continuation — provides full and complete written-description support for the impedance mapping calibration algorithm as claimed.

39. Claims 9–14 depend from Claim 1 and further define the impedance mapping calibration algorithm used by the CryoNova system to process impedance data from the integrated electrodes. The algorithm, as claimed, includes the steps of acquiring raw impedance measurements from the integrated electrodes, normalizing those measurements against a baseline, applying a temperature-dependent impedance correction, and classifying tissue state on a zone-by-zone basis.

40. I have reviewed the specification of U.S. Patent No. 11,284,561 in detail, and I can identify specific portions of that specification that describe each element of the calibration algorithm recited in Claims 9–14, as follows:

(a) Inputs to the calibration algorithm. The parent specification describes the calibration algorithm as receiving three categories of input data: (i) raw impedance measurements from each of the integrated impedance mapping electrodes, obtained by applying a low-amplitude excitation signal across each electrode pair and measuring the resulting impedance response; (ii) baseline impedance values obtained prior to the initiation of cryoablation, representing the impedance characteristics of viable, untreated tissue at body temperature; and (iii) real-time temperature data from thermocouples co-located with the impedance mapping electrodes, used to track the local temperature at each electrode site during cryoablation. These inputs are described in the parent specification at [specific column/line references to be inserted by counsel upon final review — see Exhibit B].

(b) Processing steps of the calibration algorithm. The parent specification describes the algorithm's processing steps in detail, including:

(i) Baseline normalization: The algorithm normalizes each raw impedance measurement against the corresponding baseline impedance value obtained prior to cryoablation initiation, expressing the impedance change as a ratio or percentage change from baseline. This normalization step accounts for inter-patient variability in tissue impedance and for electrode-to-electrode variability in impedance measurement characteristics. This step is described in the parent specification at [specific column/line references to be inserted by counsel upon final review — see Exhibit B].

(ii) Temperature-dependent impedance correction: The algorithm applies a correction factor to the normalized impedance measurement to compensate for the known relationship between tissue impedance and temperature. During cryoablation, the cooling of tissue causes an increase in tissue impedance that is independent of cellular injury — i.e., even viable tissue exhibits increased impedance at lower temperatures. The temperature-dependent impedance correction removes this confounding effect, isolating the impedance change attributable to tissue ablation from the impedance change attributable to temperature reduction alone. The specification describes the mathematical relationship used for this correction, which is based on empirically derived temperature-impedance coefficients obtained through bench testing with tissue-mimicking phantoms and validated with ex vivo cardiac tissue samples. This correction step is described in the parent specification at [specific column/line references to be inserted by counsel upon final review — see Exhibit B].

(iii) Threshold-based classification of tissue state: After baseline normalization and temperature correction, the algorithm compares the corrected impedance value for each electrode (and thus each cooling zone) against predefined threshold values to classify the tissue at that zone as "viable," "partially ablated," or "fully ablated." These threshold values were empirically determined through preclinical testing and represent the impedance changes associated with irreversible tissue injury as confirmed by histological analysis. This classification step is described in the parent specification at [specific column/line references to be inserted by counsel upon final review — see Exhibit B].

(c) Outputs of the calibration algorithm. The parent specification describes the algorithm as generating two categories of output: (i) a zone-by-zone tissue characterization map, which is displayed to the physician on the system console and provides a visual representation of the ablation status of each cooling zone; and (ii) adaptive control signals transmitted to the multi-zone cooling delivery system, which enable the system to automatically adjust the cooling energy delivered to each zone based on the real-time tissue characterization results. For example, a zone classified as "fully ablated" may receive a signal to reduce or cease cooling, while a zone classified as "viable" or "partially ablated" may receive a signal to maintain or increase cooling energy. These outputs are described in the parent specification at [specific column/line references to be inserted by counsel upon final review — see Exhibit B].

41. I note that annotated excerpts from U.S. Patent No. 11,284,561 identifying the specific column and line references for each of the foregoing disclosures are being prepared by counsel and will be submitted as Exhibit B to this declaration. I have reviewed drafts of these annotated excerpts and confirm that they accurately identify the relevant passages of the parent specification.

42. As the inventor who conceived and developed the impedance mapping calibration algorithm, I can confirm that the algorithm as claimed in Claims 9–14 of the '216 Application was fully described in the parent specification as filed on June 28, 2021. The parent specification describes the algorithm's inputs, processing steps, and outputs with sufficient specificity that a person of ordinary skill in the art reading the specification would have recognized that the inventors were in possession of the claimed calibration methodology at the time of filing.

43. The parent specification includes sufficient detail for a skilled artisan to implement the calibration algorithm, including the mathematical relationships for temperature-dependent impedance correction (expressed as correction functions based on empirically derived temperature-impedance coefficients) and the decision logic for tissue-state classification (expressed as threshold-based comparisons with predefined impedance change values). The specification does not merely describe the algorithm at a high level of abstraction; rather, it provides the specific technical details necessary for a person of ordinary skill in the art to understand and implement the algorithm without undue experimentation.

44. Accordingly, I respectfully submit that Claims 9–14 satisfy the written-description requirement of 35 U.S.C. § 112(a), and I ask that the Examiner reconsider the rejection of these claims in light of the specific written-description support identified herein and in Exhibit B.

VIII. Claims 15–20 — Allowable Subject Matter

45. I note that the Examiner's Non-Final Office Action indicates that Claims 15–20 contain allowable subject matter but are objected to only as depending from a rejected base claim (i.e., Claim 1). I appreciate the Examiner's recognition of the patentable merit of these dependent claims.

46. Claims 15–20 further define the integrated impedance mapping and variable-zone cooling features of the CryoNova system in ways that are consistent with and fully supported by the parent specification (U.S. Patent No. 11,284,561). The additional limitations recited in Claims 15–20 — which relate to specific structural and functional aspects of the electrode arrangement and the cooling zone configuration — are described in the parent specification with the same level of detail as the features discussed in Sections VI and VII above.

47. I understand that the Applicant intends to request that Claims 15–20 be rewritten in independent form if the base claims are amended to overcome the rejections of Claims 1–14. I support this approach and confirm that the subject matter of Claims 15–20 is independently supported by the disclosure of the parent specification.

IX. Factual Statements Regarding the CryoNova Development Program

48. I provide the following factual statements regarding the history and development of the CryoNova cryoablation catheter system to assist the Examiner in understanding the context of the claimed invention.

49. Solstice Biomedical Devices Ltd. began developing the CryoNova cryoablation catheter system in approximately 2019. The initial concept was developed by the named inventors — Dr. Connolly (myself), Dr. Tomás Brennan, and Dr. Henrik Paulsen — through a series of engineering brainstorming sessions and feasibility analyses conducted at Solstice's facility in Dublin, Ireland, between approximately March 2019 and December 2020. The parent patent application (U.S. 16/914,337) was filed on June 28, 2021, based on the technology that had been conceived and reduced to practice during this development period.

50. The CryoNova technology was independently conceived by the named inventors at Solstice Biomedical Devices Ltd. The technology was not derived from, adapted from, or inspired by the Vantage cryoablation patents or the Helios impedance mapping publication cited in the Office Action. Rather, the CryoNova system was designed from inception as a fundamentally different architecture — a multi-zone cryoablation catheter with integrated impedance sensing — that was intended to address the clinical limitations of existing single-zone balloon catheters, which the named inventors had identified through their experience in the field.

51. As noted in paragraph 3 above, Dr. Connolly and Dr. Brennan are named co-inventors on all four applications in the CryoNova patent family (parent, CON-1, CON-2, and CON-3), while Dr. Paulsen is a named co-inventor on the parent application and CON-1 only. The inventive contributions of each co-inventor are reflected in the inventorship designations for each application, which were determined in accordance with applicable patent law.

52. The CryoNova system was evaluated in two clinical studies. The European first-in-human study (n=15) was a safety and feasibility study designed to demonstrate the basic functionality and safety of the variable-zone cooling architecture with integrated impedance mapping. The U.S. pivotal IDE trial (FROST-AF, IDE No. G210047, n=220) was designed to evaluate the clinical efficacy and safety of the CryoNova system in a larger patient population under a randomized, controlled study design.

53. In the interest of full transparency, I note that the primary efficacy endpoint of the FROST-AF pivotal trial was not met. The trial's primary efficacy endpoint was freedom from documented atrial arrhythmia recurrence (atrial fibrillation, atrial flutter, or atrial tachycardia) lasting more than 30 seconds at 12 months following the ablation procedure, after a 90-day blanking period. The observed rate of freedom from atrial arrhythmia at 12 months was 58.2%, compared to the pre-specified performance target of 65%. The difference did not reach statistical significance (p = 0.14).

54. However, I wish to emphasize that the clinical trial outcome relates to clinical efficacy parameters — i.e., the therapeutic effectiveness of the cryoablation procedure in preventing arrhythmia recurrence — and does not bear on the patentability of the underlying device architecture and method claims. The claims of the '216 Application are directed to the structural and functional features of the cryoablation catheter itself, including its variable-zone cooling architecture, its integrated impedance mapping electrodes, and its calibration algorithm. The FROST-AF trial data, while not meeting the clinical efficacy target, did confirm the functionality and feasibility of the variable-zone cooling with integrated impedance mapping approach: the system successfully delivered zone-selective cryoablation with real-time impedance-based tissue characterization in all 220 enrolled patients, and the impedance mapping data correlated with post-procedure imaging results.

55. The patentability of the claims at issue does not depend on the clinical efficacy outcomes of the FROST-AF trial, and I respectfully submit that the trial results should not factor into the Examiner's evaluation of the § 103 and § 112(a) rejections.

X. Conclusion

56. Based on the foregoing, I respectfully submit that the evidence and technical explanation provided in this declaration demonstrate the following:

(1) Claims 1–8 of U.S. Patent Application No. 17/851,216 are not rendered obvious by the combination of U.S. Patent No. 10,537,418 (Vantage '418), U.S. Patent No. 9,861,432 (Vantage '432), and U.S. Publication No. 2019/0183567 (Helios '567). None of the cited references, alone or in combination, teaches or suggests the structural integration of impedance mapping electrodes into a variable-zone cryoablation catheter. The references reflect fundamentally different design paradigms — single-zone uniform cryoablation (Vantage) and standalone diagnostic impedance mapping (Helios) — and their combination does not bridge the gap to the claimed invention. Moreover, the technical challenges of impedance measurement at cryogenic temperatures are neither recognized nor addressed in the cited art, and a person of ordinary skill in the art would not have had a reasonable expectation of success in achieving the claimed integration.

(2) Claims 9–14 of U.S. Patent Application No. 17/851,216 are fully supported by the written description in the parent specification (U.S. Patent No. 11,284,561). The parent specification describes the impedance mapping calibration algorithm — including its inputs, processing steps (baseline normalization, temperature-dependent impedance correction, and threshold-based tissue-state classification), and outputs (zone-by-zone tissue characterization maps and adaptive control signals) — in sufficient detail for a person of ordinary skill in the art to recognize that the inventors were in possession of the claimed invention at the time of filing.

(3) Claims 15–20, which the Examiner has already indicated as containing allowable subject matter, are likewise supported by the parent specification and should be allowed upon resolution of the rejections of the base claims.

57. I respectfully request that the Examiner withdraw the rejections of Claims 1–14 and allow all pending Claims 1–20 of U.S. Patent Application No. 17/851,216.

XI. Verification

I declare that all statements made herein of my own knowledge are true and that all statements made on information and belief are believed to be true; and further that these statements were made with the knowledge that willful false statements and the like so made are punishable by fine or imprisonment, or both, under 18 U.S.C. § 1001 and that such willful false statements may jeopardize the validity of the application or any patent issued thereon.

________________________________________

Dr. Aisling Connolly

Date: ________

Printed Name: Dr. Aisling Connolly

Title: Vice President, Research & Development

Employer: Solstice Biomedical Devices Ltd.

Address: Unit 4, Liffey Innovation Campus, Parkgate Street, Dublin 8, D08 XR29, Ireland

Exhibit List

The following exhibits are referenced in the body of this declaration:

DOCUMENT CONTROL

DRAFT — PRIVILEGED & CONFIDENTIAL — FOR CLIENT REVIEW

Prepared by: Peter Vassiliev (Reg. No. 72,340) and Dr. Claire Nakamura (Reg. No. 66,203) Calderwood & Harkness LLP 600 Lexington Avenue, 22nd Floor New York, NY 10022

Matter No.: SBD-IP-2021-003 Client: Solstice Biomedical Devices Ltd.

NOT FOR FILING until reviewed and executed by Dr. Aisling Connolly and authorized by Ronan Gallagher, General Counsel, Solstice Biomedical Devices Ltd.

Application No.:	17/851,216 (SBD-001-CON2)
Title:	Cryoablation Catheter with Integrated Impedance Mapping Electrodes
Filing Date:	June 27, 2022
Art Unit:	3794
Primary Examiner:	James R. Dougherty
Applicant:	Solstice Biomedical Devices Ltd.
Attorney of Record:	Peter Vassiliev (Reg. No. 72,340)

Calderwood & Harkness LLP

600 Lexington Avenue, 22nd Floor

New York, NY 10022

Matter No.:	SBD-IP-2021-003
Exhibit	Description	Status
Exhibit A	Curriculum Vitae of Dr. Aisling Connolly	Referenced; to be attached upon execution
Exhibit B	Annotated excerpts from U.S. Patent No. 11,284,561 identifying written-description support for the impedance mapping calibration algorithm (Claims 9–14)	To be prepared by counsel (P. Vassiliev / C. Nakamura) and reviewed by declarant prior to filing
Exhibit C	Comparison chart of CryoNova variable-zone architecture vs. Vantage single-zone balloon design	Referenced from claim amendment chart prepared by Wendy Schultz; to be finalized

DRAFT — PRIVILEGED & CONFIDENTIAL — FOR CLIENT REVIEW Prepared by: Peter Vassiliev (Reg. No. 72,340) and Dr. Claire Nakamura (Reg. No. 66,203) Calderwood & Harkness LLP | 600 Lexington Avenue, 22nd Floor, New York, NY 10022 Matter No.: SBD-IP-2021-003 Client: Solstice Biomedical Devices Ltd. Not for filing until reviewed and executed by Dr. Connolly and authorized by Ronan Gallagher, General Counsel
IN THE UNITED STATES PATENT AND TRADEMARK OFFICE
DECLARATION OF DR. AISLING CONNOLLY UNDER 37 C.F.R. § 1.132
I. Introduction and Identity of Declarant
1.  My name is Dr. Aisling Connolly. I am a citizen of Ireland. I am currently employed as Vice President of Research & Development at Solstice Biomedical Devices Ltd. ("Solstice" or "SBD"), with offices located at Unit 4, Liffey Innovation Campus, Parkgate Street, Dublin 8, D08 XR29, Ireland. I am over eighteen (18) years of age and am competent to make this declaration. The facts set forth herein are based on my personal knowledge, my review of the relevant patent documents, and my professional experience in the field of cardiac cryoablation and electrophysiology mapping technologies. If called upon to testify, I could and would testify competently to the matters stated herein.
2.  I make this declaration under 37 C.F.R. § 1.132 in support of the patentability of the claims currently pending in U.S. Patent Application No. 17/851,216, entitled "Cryoablation Catheter with Integrated Impedance Mapping Electrodes" (hereinafter, the "'216 Application" or "CON-2"). This declaration is submitted in connection with the Applicant's response to the Non-Final Office Action mailed by the United States Patent and Trademark Office ("USPTO") on September 15, 2024.
3.  I am a named co-inventor on all four applications in the CryoNova patent family, which consists of the following related applications and patents:
(a) U.S. Patent Application No. 16/914,337, filed June 28, 2021, now issued as U.S. Patent No. 11,284,561 (the "parent application" or the "'561 Patent");
(b) U.S. Patent Application No. 17/702,489 ("CON-1"), a continuation of the parent application;
(c) U.S. Patent Application No. 17/851,216 ("CON-2"), the application at issue in this declaration, also a continuation of the parent application; and
(d) U.S. Patent Application No. 18/109,744 ("CON-3"), likewise a continuation of the parent application.
4.  The co-inventors on the CryoNova patent family are as follows:
(a) Dr. Tomás Brennan, Chief Medical Officer and Co-Founder of Solstice Biomedical Devices Ltd., is a named co-inventor on all four applications in the CryoNova patent family (i.e., the parent application, CON-1, CON-2, and CON-3).
(b) Dr. Henrik Paulsen, formerly a Senior Engineer at Solstice Biomedical Devices Ltd. and currently employed at Arclight Therapeutics GmbH, is a named co-inventor on the parent application (U.S. 16/914,337, now U.S. Patent No. 11,284,561) and on CON-1 (U.S. 17/702,489) only. Dr. Paulsen is not a named co-inventor on CON-2 or CON-3.
5.  The assignee of the '216 Application and all other applications in the CryoNova patent family is Solstice Biomedical Devices Ltd., an Irish private limited company registered with the Companies Registration Office of Ireland under CRO No. 647832.
II. Qualifications and Technical Background of Declarant
6.  I hold a Ph.D. in Biomedical Engineering from Trinity College Dublin, which I received in 2009. My doctoral research focused on the thermal modeling of cryogenic tissue ablation and the design of cryoprobe tip geometries for cardiac applications. A copy of my full curriculum vitae is attached hereto as Exhibit A.
7.  I have over fifteen (15) years of experience in medical device research and development, with a particular specialization in cardiac cryoablation catheter design and electrophysiology mapping technologies. Throughout my career, I have been involved in the design, prototyping, pre-clinical testing, and clinical evaluation of catheter-based systems for the treatment of cardiac arrhythmias, including atrial fibrillation, atrial flutter, and ventricular tachycardia.
8.  In my current role as Vice President of Research & Development at Solstice Biomedical Devices Ltd., I lead the engineering team responsible for the design, development, and testing of the CryoNova cryoablation catheter system. This team currently comprises twenty-three (23) engineers and scientists across the disciplines of mechanical engineering, electrical engineering, software engineering, and biomedical engineering. I have held this position since 2018, when I joined Solstice as one of the company's earliest technical hires.
9.  I personally led the development of the variable-zone cooling architecture and the integrated impedance mapping electrode array that are the subject of the claims pending in the '216 Application. In this capacity, I was responsible for the initial concept definition, the iterative engineering design process, the bench testing and verification protocols, and the coordination with external regulatory and clinical affairs consultants in preparation for clinical evaluation.
10.  I am familiar with the current state of the art in cryoablation catheter technology as it pertains to pulmonary vein isolation for the treatment of atrial fibrillation. This familiarity extends to competing commercial products and patent portfolios, including those of Vantage Cryosurgical Systems, Inc. ("Vantage"), Cascade Holdings, Greaves Corporation, and others. I have reviewed published clinical literature, issued patents, and patent application publications relating to cryoablation balloon catheter design, impedance-based tissue characterization, and electrophysiology mapping catheters.
11.  In addition to my design and development responsibilities, I served as the engineering and technical lead during the European first-in-human clinical study of the CryoNova system. That study enrolled fifteen (15) patients at two investigational sites in Ireland and the Netherlands and was conducted under European regulatory authorization. I subsequently served as the technical lead during the United States pivotal Investigational Device Exemption ("IDE") trial of the CryoNova system, designated as the FROST-AF trial (IDE No. G210047), which enrolled two hundred and twenty (220) patients at fourteen (14) investigational sites across the United States.
12.  In preparation for this declaration, I have reviewed the following documents:
(a) The Non-Final Office Action mailed September 15, 2024, in connection with U.S. Patent Application No. 17/851,216;
(b) The pending claims (Claims 1–20) of U.S. Patent Application No. 17/851,216, as filed;
(c) U.S. Patent No. 10,537,418, assigned to Vantage Cryosurgical Systems, Inc. (hereinafter, the "Vantage '418 patent" or "'418 patent");
(d) U.S. Patent No. 9,861,432, assigned to Vantage Cryosurgical Systems, Inc. (hereinafter, the "Vantage '432 patent" or "'432 patent");
(e) U.S. Patent Application Publication No. 2019/0183567, assigned to Helios Surgical Technologies, Inc. (hereinafter, the "Helios '567 publication" or "'567 publication");
(f) U.S. Patent No. 11,284,561, the parent patent in the CryoNova family (hereinafter, the "'561 Patent"); and
(g) The complete specification and prosecution history of U.S. Patent Application No. 17/851,216.
III. Purpose of Declaration
13.  The purpose of this declaration is to provide the Examiner with factual evidence and technical context regarding the following matters:
(A) The distinctions between the claimed CryoNova cryoablation catheter system with integrated impedance mapping electrodes and the prior-art references cited in the Non-Final Office Action mailed September 15, 2024; and
(B) The full written-description support in the parent specification (U.S. Patent No. 11,284,561) for the impedance mapping calibration algorithm recited in Claims 9–14 of the '216 Application.
14.  Specifically, this declaration addresses the following rejections and objections set forth in the Non-Final Office Action:
(i) Claims 1–8 — rejected under 35 U.S.C. § 103 as allegedly obvious over U.S. Patent No. 10,537,418 ("Vantage '418") in view of U.S. Patent No. 9,861,432 ("Vantage '432") and U.S. Publication No. 2019/0183567 ("Helios '567");
(ii) Claims 9–14 — rejected under 35 U.S.C. § 112(a) for alleged lack of written description regarding the impedance mapping calibration algorithm recited in those claims; and
(iii) Claims 15–20 — objected to as depending from a rejected base claim, but indicated by the Examiner as containing allowable subject matter.
15.  I respectfully submit this declaration to assist the Examiner in evaluating the technical merits of the pending claims and to provide the perspective of a named co-inventor who personally conceived and developed the technology at issue.
IV. Overview of the CryoNova Technology
16.  The CryoNova cryoablation catheter system is a second-generation cryoablation catheter designed for pulmonary vein isolation ("PVI") in the treatment of atrial fibrillation. Atrial fibrillation is the most common sustained cardiac arrhythmia, affecting millions of patients worldwide, and catheter-based ablation of the pulmonary veins has become an established treatment strategy for drug-refractory cases. The CryoNova system was developed at Solstice Biomedical Devices Ltd. to address specific clinical and technical limitations observed with existing single-zone cryoablation balloon catheters.
17.  The first key differentiating feature of the CryoNova system is its variable-zone cooling architecture. Unlike conventional single-zone balloon catheters — which apply a uniform circumferential cryoablation energy across the entire contact surface — the CryoNova catheter incorporates multiple discrete cooling zones that can be independently activated, deactivated, or modulated. This variable-zone architecture enables the physician to selectively cryoablate specific tissue segments around the pulmonary vein ostium, concentrating ablation energy on areas requiring treatment while sparing areas where ablation is unnecessary or where critical anatomical structures (such as the phrenic nerve or esophagus) are at risk of collateral injury.
18.  The second key differentiating feature of the CryoNova system is its integrated impedance mapping electrodes. These electrodes are embedded directly within the catheter body, positioned adjacent to and co-located with the discrete cooling zones. The integrated electrodes allow real-time tissue impedance measurements to be taken during the cryoablation procedure itself, enabling the physician to monitor lesion formation progress and assess tissue contact quality in real time, without requiring the insertion or manipulation of a separate diagnostic mapping catheter. This integration eliminates the need for catheter exchanges during the procedure, reduces procedural complexity, and provides impedance data that is spatially registered to the ablation zones.
19.  The third key differentiating feature of the CryoNova system is its impedance mapping calibration algorithm. This algorithm processes the impedance data collected by the integrated electrodes and distinguishes between viable myocardial tissue and tissue that has been successfully ablated. The algorithm accounts for the temperature-dependent changes in tissue impedance that occur during cryoablation — a factor that is not present in room-temperature or body-temperature impedance mapping systems. The output of the calibration algorithm is a zone-by-zone tissue characterization map, which is provided to the system's control unit as a feedback loop for adaptive multi-zone cryoablation delivery. In this way, the CryoNova system can automatically adjust the cooling energy delivered to each zone based on real-time tissue characterization, creating a closed-loop ablation system.
20.  These three features — variable-zone cooling architecture, integrated impedance mapping electrodes, and the impedance mapping calibration algorithm — are the subject of the claims in the CryoNova patent family. The '216 Application (CON-2) is specifically directed to the catheter structure incorporating the integrated impedance mapping electrodes and their arrangement relative to the variable-zone cooling architecture, as well as the calibration algorithm that enables real-time tissue characterization during cryoablation.
V. Discussion of the Cited Prior Art
21.  In this section, I provide my technical analysis of each of the three prior-art references cited in the Non-Final Office Action, based on my review of those references and my familiarity with the field.
V.A. U.S. Patent No. 10,537,418 (Vantage Cryosurgical Systems, Inc.)
22.  U.S. Patent No. 10,537,418 (the "Vantage '418 patent") is assigned to Vantage Cryosurgical Systems, Inc., which I understand to be located at 1420 Gateway Boulevard, South San Francisco, California 94080. The Vantage '418 patent describes a cryoablation balloon catheter designed for pulmonary vein isolation.
23.  The cryoablation catheter disclosed in the Vantage '418 patent is a single-zone cryoablation balloon catheter. The balloon described in the '418 patent is a compliant balloon that is designed to conform to the anatomical contour of the pulmonary vein ostium upon inflation and to deliver a uniform circumferential cryoablation energy to the tissue in contact with the balloon surface. The entire balloon acts as a single cooling zone — there is no teaching, suggestion, or disclosure in the '418 patent of dividing the balloon into discrete, independently controllable cooling zones.
24.  Critically, the Vantage '418 patent does not teach or suggest any form of integrated impedance mapping electrodes within the catheter body. The '418 patent does not describe the use of impedance-based measurements for tissue characterization, lesion assessment, or contact quality monitoring. To the extent that the '418 patent describes any form of tissue or procedural monitoring, such monitoring is limited to temperature sensors (thermocouples) that measure the temperature of the balloon surface or the adjacent tissue during cryoablation. Temperature-based monitoring provides only an indirect and imprecise indicator of lesion formation; it does not provide the impedance-based tissue characterization that is central to the CryoNova system's claims.
25.  In my professional opinion, a person of ordinary skill in the art reading the Vantage '418 patent would understand it to be directed to a fundamentally different design approach from the CryoNova system. The '418 patent embodies the conventional single-zone balloon cryoablation paradigm — uniform circumferential cooling applied to the entire pulmonary vein ostium — without any motivation or suggestion to deviate from that paradigm by introducing variable-zone cooling or integrated impedance sensing. The absence of any impedance-related disclosure in the '418 patent is significant: it reflects the fact that the Vantage approach was not conceived as a platform for real-time tissue characterization, and there is nothing in the '418 patent that would lead a skilled artisan toward the integration of impedance mapping electrodes into a cryoablation catheter.
V.B. U.S. Patent No. 9,861,432 (Vantage Cryosurgical Systems, Inc.)
26.  U.S. Patent No. 9,861,432 (the "Vantage '432 patent") is also assigned to Vantage Cryosurgical Systems, Inc. The '432 patent describes improvements to cryoablation balloon catheter construction, including innovations in balloon wall materials, refrigerant delivery mechanisms, and methods for enhancing the thermal performance of the balloon during cryoablation.
27.  The '432 patent is directed to enhancing the uniformity and efficiency of the single-zone cooling approach described in related Vantage patents, including the '418 patent. The improvements disclosed in the '432 patent — such as multi-layer balloon wall constructions for improved thermal conductivity and modified refrigerant injection patterns for more uniform cooling — are all directed to optimizing the performance of a single, uniform cooling zone. None of these improvements relate to dividing the balloon into multiple independently controllable cooling zones, nor do they relate to any form of impedance-based tissue sensing or characterization.
28.  Like the '418 patent, the Vantage '432 patent does not disclose or suggest impedance mapping electrodes integrated into the catheter body. The '432 patent does not address tissue characterization through impedance measurement, does not describe any electrode configuration for that purpose, and does not discuss the challenges associated with impedance measurement in a cryogenic environment.
29.  In my professional opinion, combining the teachings of the Vantage '432 patent with those of the Vantage '418 patent would yield, at most, an improved single-zone cryoablation balloon — i.e., a balloon with better materials and more uniform cooling, but still fundamentally a single-zone design without impedance mapping capability. There is no teaching, suggestion, or motivation in either the '418 patent or the '432 patent to incorporate impedance mapping electrodes into the catheter body, and the combination of these two references does not bridge the gap between their disclosures and the claims of the '216 Application.
V.C. U.S. Publication No. 2019/0183567 (Helios Surgical Technologies, Inc.)
30.  U.S. Patent Application Publication No. 2019/0183567 (the "Helios '567 publication") is assigned to Helios Surgical Technologies, Inc., which I understand to be located at 750 Bering Drive, Suite 400, Houston, Texas 77057. The Helios '567 publication describes a standalone diagnostic impedance mapping catheter for use in cardiac electrophysiology procedures.
31.  The Helios '567 publication teaches the concept of using impedance-based measurements to characterize cardiac tissue. Specifically, the Helios catheter is described as a multi-electrode catheter that is introduced into the cardiac chambers to generate impedance maps of the endocardial surface. These impedance maps can be used by the physician to identify areas of viable tissue, scar tissue, and transitional tissue (such as the border zones of prior ablation lesions).
32.  However, the Helios '567 publication describes this impedance mapping functionality exclusively in the context of a separate, standalone diagnostic mapping catheter — not in the context of a cryoablation catheter or any other therapeutic ablation device. The Helios catheter is designed to be used as a diagnostic tool, either before or after an ablation procedure, to assess the cardiac substrate. It is not designed to deliver ablation energy of any kind, and it is not designed to operate simultaneously with an ablation catheter.
33.  Importantly, the Helios '567 publication does not teach or suggest integrating impedance mapping electrodes into a cryoablation catheter. Nor does the Helios publication describe or address the specific technical challenges that arise when impedance measurements are performed during active cryoablation. These challenges include, but are not limited to:
(a) Electrode signal degradation at cryogenic temperatures: The electrical properties of electrode materials and electrode-tissue interfaces change significantly at cryogenic temperatures (typically −40°C to −80°C at the balloon surface during cryoablation). These changes can cause baseline shifts, increased noise, and reduced signal fidelity in impedance measurements, effects that are not encountered in the body-temperature environment for which the Helios catheter was designed.
(b) Thermal artifact compensation: During active cryoablation, the tissue impedance changes not only as a function of cellular injury (the parameter of interest for lesion assessment) but also as a direct function of temperature reduction. Separating the temperature-dependent impedance change from the lesion-dependent impedance change requires a specialized calibration algorithm — the very algorithm recited in Claims 9–14 — that is neither described nor suggested in the Helios publication.
(c) Mechanical integration challenges: Incorporating impedance mapping electrodes into the surface of a compliant or semi-compliant cryoablation balloon presents mechanical design challenges that are entirely distinct from the electrode placement considerations in a conventional mapping catheter. These challenges include maintaining electrode contact with tissue during balloon inflation and deflation, routing electrical conductors through the catheter shaft without interfering with refrigerant delivery pathways, and ensuring that the electrodes do not compromise the structural integrity of the balloon wall.
34.  In my professional opinion, a person of ordinary skill in the art would not have been motivated to combine the impedance mapping concept of the Helios '567 publication with the single-zone cryoablation balloon concepts of the Vantage '418 and '432 patents. The reasons for this conclusion are threefold:
(i) The physical integration of impedance electrodes into a cryoablation balloon presents distinct engineering challenges that are not addressed, recognized, or contemplated in any of the three cited references. A skilled artisan would have recognized these challenges as substantial obstacles to any such combination.
(ii) The Helios device is explicitly designed to function at body temperature (approximately 37°C), not at the cryogenic temperatures (approximately −40°C to −80°C) encountered during cryoablation. The impedance measurement techniques described in the Helios publication are not validated for, nor adapted to, operation at cryogenic temperatures. A skilled artisan would have understood that simply placing Helios-type electrodes on a Vantage-type balloon would not yield a functional impedance mapping system during active cryoablation without substantial additional inventive work, including the development of a temperature-compensation calibration algorithm.
(iii) There is no suggestion in any of the three cited references that impedance mapping and cryoablation delivery should occur from the same catheter simultaneously. The conventional clinical workflow in the art at the relevant time involved using separate catheters for mapping and ablation — a practice that the CryoNova system was specifically designed to improve upon. The cited references reflect this conventional separation-of-function paradigm and do not suggest departing from it.
VI. Distinctions Between the Claimed Invention and the Prior Art — Claims 1–8 (§ 103 Rejection)
35.  Claims 1–8 of the '216 Application recite a cryoablation catheter with integrated impedance mapping electrodes arranged in a specific configuration that enables simultaneous cryoablation delivery and real-time impedance-based tissue characterization. Independent Claim 1, in particular, recites a cryoablation catheter comprising a catheter body, an expandable cryoablation element having a plurality of discrete cooling zones, a plurality of impedance mapping electrodes integrated into the catheter body and positioned adjacent to respective discrete cooling zones, and electrical conductors coupling the impedance mapping electrodes to a control unit. Claims 2–8 depend from Claim 1 and further define the specific arrangement, number, and configuration of the impedance mapping electrodes relative to the cooling zones, as well as structural features of the catheter body that facilitate simultaneous ablation and impedance sensing.
36.  Based on my review of the cited references and my understanding of the claimed invention, I respectfully submit that the combination of the Vantage '418 patent, the Vantage '432 patent, and the Helios '567 publication does not render Claims 1–8 obvious. My technical basis for this opinion is as follows:
(1) No reference, alone or in combination, discloses or suggests the structural integration of impedance mapping electrodes within a cryoablation catheter body. As discussed in Section V above, the Vantage '418 and '432 patents do not disclose impedance mapping electrodes of any kind. The Helios '567 publication discloses impedance mapping electrodes, but only in the context of a standalone diagnostic mapping catheter — not integrated into a cryoablation catheter. None of the three references teaches or suggests that impedance mapping electrodes should be incorporated into the physical structure of a cryoablation catheter so as to enable simultaneous ablation and impedance sensing from a single device.
(2) The variable-zone cooling feature of the CryoNova design is not taught or suggested by the uniform single-zone Vantage balloon design. Claims 1–8 recite a cryoablation element having "a plurality of discrete cooling zones." This feature is a foundational structural element of the claimed invention and is directly related to the arrangement of the impedance mapping electrodes, which are positioned "adjacent to respective discrete cooling zones" for zone-by-zone impedance monitoring. The Vantage '418 and '432 patents disclose only a single, uniform cooling zone. A person of ordinary skill in the art reading the Vantage patents would not have been motivated to redesign the single-zone balloon as a multi-zone balloon, because the entire thrust of the Vantage approach is directed to optimizing uniform circumferential cooling.
(3) The specific electrode arrangement claimed in Claims 1–8 has no analog in any of the cited references. Claims 1–8 recite impedance mapping electrodes that are specifically positioned adjacent to discrete cooling zones for zone-by-zone impedance monitoring. This spatial co-registration of electrodes with cooling zones is a structural feature that enables the CryoNova system's unique capability of providing zone-specific tissue characterization data during cryoablation. The Helios publication describes a multi-electrode mapping catheter, but the electrode arrangement in the Helios catheter is designed for general endocardial surface mapping and is not configured for zone-by-zone monitoring in coordination with discrete cooling zones. There is no analog in any of the cited references for the specific electrode-to-cooling-zone spatial relationship recited in the claims.
(4) The technical challenges of impedance measurement at cryogenic temperatures are neither recognized nor addressed in the cited art. As I discussed in paragraphs 33–34 above, performing impedance measurements during active cryoablation introduces technical challenges — including electrode signal degradation at cryogenic temperatures, thermal artifact compensation, and mechanical integration challenges — that are entirely absent from the disclosures of the cited references. A person of ordinary skill in the art would have recognized these challenges as significant barriers to the combination proposed in the Office Action and would not have had a reasonable expectation of success in achieving the claimed integration without the inventive contributions reflected in the '216 Application.
37.  In addition to the foregoing technical distinctions, I wish to provide the Examiner with further evidence of the non-obvious character of the claimed invention. The CryoNova system's integration of impedance mapping electrodes into a variable-zone cryoablation catheter was not achieved through routine engineering or straightforward combination of known elements. Rather, the development required extensive engineering iteration over a period of approximately two years (2019–2021), involving multiple prototype iterations, systematic bench testing under simulated cryogenic conditions, and ultimately a first-in-human clinical study in Europe (n=15 patients) to validate the feasibility and functionality of the integrated approach. The challenges encountered during this development process — particularly with respect to maintaining reliable impedance measurements during active cryoablation — confirmed that the integration required inventive effort that went well beyond routine skill in the art. These development challenges are documented in internal Solstice engineering records and could be made available for the Examiner's review if requested.
VII. Written-Description Support for the Impedance Mapping Calibration Algorithm — Claims 9–14 (§ 112(a) Rejection)
38.  The Examiner rejected Claims 9–14 under 35 U.S.C. § 112(a) for alleged lack of written description regarding the impedance mapping calibration algorithm recited in those claims. I respectfully submit that the parent specification — i.e., the specification of U.S. Patent No. 11,284,561, from which the '216 Application claims priority as a continuation — provides full and complete written-description support for the impedance mapping calibration algorithm as claimed.
39.  Claims 9–14 depend from Claim 1 and further define the impedance mapping calibration algorithm used by the CryoNova system to process impedance data from the integrated electrodes. The algorithm, as claimed, includes the steps of acquiring raw impedance measurements from the integrated electrodes, normalizing those measurements against a baseline, applying a temperature-dependent impedance correction, and classifying tissue state on a zone-by-zone basis.
40.  I have reviewed the specification of U.S. Patent No. 11,284,561 in detail, and I can identify specific portions of that specification that describe each element of the calibration algorithm recited in Claims 9–14, as follows:
(a) Inputs to the calibration algorithm. The parent specification describes the calibration algorithm as receiving three categories of input data: (i) raw impedance measurements from each of the integrated impedance mapping electrodes, obtained by applying a low-amplitude excitation signal across each electrode pair and measuring the resulting impedance response; (ii) baseline impedance values obtained prior to the initiation of cryoablation, representing the impedance characteristics of viable, untreated tissue at body temperature; and (iii) real-time temperature data from thermocouples co-located with the impedance mapping electrodes, used to track the local temperature at each electrode site during cryoablation. These inputs are described in the parent specification at [specific column/line references to be inserted by counsel upon final review — see Exhibit B].
(b) Processing steps of the calibration algorithm. The parent specification describes the algorithm's processing steps in detail, including:
(i) Baseline normalization: The algorithm normalizes each raw impedance measurement against the corresponding baseline impedance value obtained prior to cryoablation initiation, expressing the impedance change as a ratio or percentage change from baseline. This normalization step accounts for inter-patient variability in tissue impedance and for electrode-to-electrode variability in impedance measurement characteristics. This step is described in the parent specification at [specific column/line references to be inserted by counsel upon final review — see Exhibit B].
(ii) Temperature-dependent impedance correction: The algorithm applies a correction factor to the normalized impedance measurement to compensate for the known relationship between tissue impedance and temperature. During cryoablation, the cooling of tissue causes an increase in tissue impedance that is independent of cellular injury — i.e., even viable tissue exhibits increased impedance at lower temperatures. The temperature-dependent impedance correction removes this confounding effect, isolating the impedance change attributable to tissue ablation from the impedance change attributable to temperature reduction alone. The specification describes the mathematical relationship used for this correction, which is based on empirically derived temperature-impedance coefficients obtained through bench testing with tissue-mimicking phantoms and validated with ex vivo cardiac tissue samples. This correction step is described in the parent specification at [specific column/line references to be inserted by counsel upon final review — see Exhibit B].
(iii) Threshold-based classification of tissue state: After baseline normalization and temperature correction, the algorithm compares the corrected impedance value for each electrode (and thus each cooling zone) against predefined threshold values to classify the tissue at that zone as "viable," "partially ablated," or "fully ablated." These threshold values were empirically determined through preclinical testing and represent the impedance changes associated with irreversible tissue injury as confirmed by histological analysis. This classification step is described in the parent specification at [specific column/line references to be inserted by counsel upon final review — see Exhibit B].
(c) Outputs of the calibration algorithm. The parent specification describes the algorithm as generating two categories of output: (i) a zone-by-zone tissue characterization map, which is displayed to the physician on the system console and provides a visual representation of the ablation status of each cooling zone; and (ii) adaptive control signals transmitted to the multi-zone cooling delivery system, which enable the system to automatically adjust the cooling energy delivered to each zone based on the real-time tissue characterization results. For example, a zone classified as "fully ablated" may receive a signal to reduce or cease cooling, while a zone classified as "viable" or "partially ablated" may receive a signal to maintain or increase cooling energy. These outputs are described in the parent specification at [specific column/line references to be inserted by counsel upon final review — see Exhibit B].
41.  I note that annotated excerpts from U.S. Patent No. 11,284,561 identifying the specific column and line references for each of the foregoing disclosures are being prepared by counsel and will be submitted as Exhibit B to this declaration. I have reviewed drafts of these annotated excerpts and confirm that they accurately identify the relevant passages of the parent specification.
42.  As the inventor who conceived and developed the impedance mapping calibration algorithm, I can confirm that the algorithm as claimed in Claims 9–14 of the '216 Application was fully described in the parent specification as filed on June 28, 2021. The parent specification describes the algorithm's inputs, processing steps, and outputs with sufficient specificity that a person of ordinary skill in the art reading the specification would have recognized that the inventors were in possession of the claimed calibration methodology at the time of filing.
43.  The parent specification includes sufficient detail for a skilled artisan to implement the calibration algorithm, including the mathematical relationships for temperature-dependent impedance correction (expressed as correction functions based on empirically derived temperature-impedance coefficients) and the decision logic for tissue-state classification (expressed as threshold-based comparisons with predefined impedance change values). The specification does not merely describe the algorithm at a high level of abstraction; rather, it provides the specific technical details necessary for a person of ordinary skill in the art to understand and implement the algorithm without undue experimentation.
44.  Accordingly, I respectfully submit that Claims 9–14 satisfy the written-description requirement of 35 U.S.C. § 112(a), and I ask that the Examiner reconsider the rejection of these claims in light of the specific written-description support identified herein and in Exhibit B.
VIII. Claims 15–20 — Allowable Subject Matter
45.  I note that the Examiner's Non-Final Office Action indicates that Claims 15–20 contain allowable subject matter but are objected to only as depending from a rejected base claim (i.e., Claim 1). I appreciate the Examiner's recognition of the patentable merit of these dependent claims.
46.  Claims 15–20 further define the integrated impedance mapping and variable-zone cooling features of the CryoNova system in ways that are consistent with and fully supported by the parent specification (U.S. Patent No. 11,284,561). The additional limitations recited in Claims 15–20 — which relate to specific structural and functional aspects of the electrode arrangement and the cooling zone configuration — are described in the parent specification with the same level of detail as the features discussed in Sections VI and VII above.
47.  I understand that the Applicant intends to request that Claims 15–20 be rewritten in independent form if the base claims are amended to overcome the rejections of Claims 1–14. I support this approach and confirm that the subject matter of Claims 15–20 is independently supported by the disclosure of the parent specification.
IX. Factual Statements Regarding the CryoNova Development Program
48.  I provide the following factual statements regarding the history and development of the CryoNova cryoablation catheter system to assist the Examiner in understanding the context of the claimed invention.
49.  Solstice Biomedical Devices Ltd. began developing the CryoNova cryoablation catheter system in approximately 2019. The initial concept was developed by the named inventors — Dr. Connolly (myself), Dr. Tomás Brennan, and Dr. Henrik Paulsen — through a series of engineering brainstorming sessions and feasibility analyses conducted at Solstice's facility in Dublin, Ireland, between approximately March 2019 and December 2020. The parent patent application (U.S. 16/914,337) was filed on June 28, 2021, based on the technology that had been conceived and reduced to practice during this development period.
50.  The CryoNova technology was independently conceived by the named inventors at Solstice Biomedical Devices Ltd. The technology was not derived from, adapted from, or inspired by the Vantage cryoablation patents or the Helios impedance mapping publication cited in the Office Action. Rather, the CryoNova system was designed from inception as a fundamentally different architecture — a multi-zone cryoablation catheter with integrated impedance sensing — that was intended to address the clinical limitations of existing single-zone balloon catheters, which the named inventors had identified through their experience in the field.
51.  As noted in paragraph 3 above, Dr. Connolly and Dr. Brennan are named co-inventors on all four applications in the CryoNova patent family (parent, CON-1, CON-2, and CON-3), while Dr. Paulsen is a named co-inventor on the parent application and CON-1 only. The inventive contributions of each co-inventor are reflected in the inventorship designations for each application, which were determined in accordance with applicable patent law.
52.  The CryoNova system was evaluated in two clinical studies. The European first-in-human study (n=15) was a safety and feasibility study designed to demonstrate the basic functionality and safety of the variable-zone cooling architecture with integrated impedance mapping. The U.S. pivotal IDE trial (FROST-AF, IDE No. G210047, n=220) was designed to evaluate the clinical efficacy and safety of the CryoNova system in a larger patient population under a randomized, controlled study design.
53.  In the interest of full transparency, I note that the primary efficacy endpoint of the FROST-AF pivotal trial was not met. The trial's primary efficacy endpoint was freedom from documented atrial arrhythmia recurrence (atrial fibrillation, atrial flutter, or atrial tachycardia) lasting more than 30 seconds at 12 months following the ablation procedure, after a 90-day blanking period. The observed rate of freedom from atrial arrhythmia at 12 months was 58.2%, compared to the pre-specified performance target of 65%. The difference did not reach statistical significance (p = 0.14).
54.  However, I wish to emphasize that the clinical trial outcome relates to clinical efficacy parameters — i.e., the therapeutic effectiveness of the cryoablation procedure in preventing arrhythmia recurrence — and does not bear on the patentability of the underlying device architecture and method claims. The claims of the '216 Application are directed to the structural and functional features of the cryoablation catheter itself, including its variable-zone cooling architecture, its integrated impedance mapping electrodes, and its calibration algorithm. The FROST-AF trial data, while not meeting the clinical efficacy target, did confirm the functionality and feasibility of the variable-zone cooling with integrated impedance mapping approach: the system successfully delivered zone-selective cryoablation with real-time impedance-based tissue characterization in all 220 enrolled patients, and the impedance mapping data correlated with post-procedure imaging results.
55.  The patentability of the claims at issue does not depend on the clinical efficacy outcomes of the FROST-AF trial, and I respectfully submit that the trial results should not factor into the Examiner's evaluation of the § 103 and § 112(a) rejections.
X. Conclusion
56.  Based on the foregoing, I respectfully submit that the evidence and technical explanation provided in this declaration demonstrate the following:
(1) Claims 1–8 of U.S. Patent Application No. 17/851,216 are not rendered obvious by the combination of U.S. Patent No. 10,537,418 (Vantage '418), U.S. Patent No. 9,861,432 (Vantage '432), and U.S. Publication No. 2019/0183567 (Helios '567). None of the cited references, alone or in combination, teaches or suggests the structural integration of impedance mapping electrodes into a variable-zone cryoablation catheter. The references reflect fundamentally different design paradigms — single-zone uniform cryoablation (Vantage) and standalone diagnostic impedance mapping (Helios) — and their combination does not bridge the gap to the claimed invention. Moreover, the technical challenges of impedance measurement at cryogenic temperatures are neither recognized nor addressed in the cited art, and a person of ordinary skill in the art would not have had a reasonable expectation of success in achieving the claimed integration.
(2) Claims 9–14 of U.S. Patent Application No. 17/851,216 are fully supported by the written description in the parent specification (U.S. Patent No. 11,284,561). The parent specification describes the impedance mapping calibration algorithm — including its inputs, processing steps (baseline normalization, temperature-dependent impedance correction, and threshold-based tissue-state classification), and outputs (zone-by-zone tissue characterization maps and adaptive control signals) — in sufficient detail for a person of ordinary skill in the art to recognize that the inventors were in possession of the claimed invention at the time of filing.
(3) Claims 15–20, which the Examiner has already indicated as containing allowable subject matter, are likewise supported by the parent specification and should be allowed upon resolution of the rejections of the base claims.
57.  I respectfully request that the Examiner withdraw the rejections of Claims 1–14 and allow all pending Claims 1–20 of U.S. Patent Application No. 17/851,216.
XI. Verification
I declare that all statements made herein of my own knowledge are true and that all statements made on information and belief are believed to be true; and further that these statements were made with the knowledge that willful false statements and the like so made are punishable by fine or imprisonment, or both, under 18 U.S.C. § 1001 and that such willful false statements may jeopardize the validity of the application or any patent issued thereon.
________________________________________
Dr. Aisling Connolly
Date: ________
Printed Name: Dr. Aisling Connolly
Title: Vice President, Research & Development
Employer: Solstice Biomedical Devices Ltd.
Address: Unit 4, Liffey Innovation Campus, Parkgate Street, Dublin 8, D08 XR29, Ireland
Exhibit List
The following exhibits are referenced in the body of this declaration:
DOCUMENT CONTROL
DRAFT — PRIVILEGED & CONFIDENTIAL — FOR CLIENT REVIEW
Prepared by: Peter Vassiliev (Reg. No. 72,340) and Dr. Claire Nakamura (Reg. No. 66,203) Calderwood & Harkness LLP 600 Lexington Avenue, 22nd Floor New York, NY 10022
Matter No.: SBD-IP-2021-003 Client: Solstice Biomedical Devices Ltd.
NOT FOR FILING until reviewed and executed by Dr. Aisling Connolly and authorized by Ronan Gallagher, General Counsel, Solstice Biomedical Devices Ltd.
Application No.: | 17/851,216 (SBD-001-CON2)
Title: | Cryoablation Catheter with Integrated Impedance Mapping Electrodes
Filing Date: | June 27, 2022
Art Unit: | 3794
Primary Examiner: | James R. Dougherty
Applicant: | Solstice Biomedical Devices Ltd.
Attorney of Record: | Peter Vassiliev (Reg. No. 72,340)
Calderwood & Harkness LLP
600 Lexington Avenue, 22nd Floor
New York, NY 10022
Matter No.: | SBD-IP-2021-003
Exhibit | Description | Status
Exhibit A | Curriculum Vitae of Dr. Aisling Connolly | Referenced; to be attached upon execution
Exhibit B | Annotated excerpts from U.S. Patent No. 11,284,561 identifying written-description support for the impedance mapping calibration algorithm (Claims 9–14) | To be prepared by counsel (P. Vassiliev / C. Nakamura) and reviewed by declarant prior to filing
Exhibit C | Comparison chart of CryoNova variable-zone architecture vs. Vantage single-zone balloon design | Referenced from claim amendment chart prepared by Wendy Schultz; to be finalized

IN THE UNITED STATES PATENT AND TRADEMARK OFFICE

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