Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of the Claims
Claims 249-284 are pending.
Claims 271-284 are withdrawn (see election/restriction)
Priority
Applicant’s claim for benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) is acknowledged. This application claims priority to PRO application 63/286,861, filed 12/07/2021.
Information Disclosure Statement
Applicant has not filed an IDS as of 6/27/2026.
Election/Restrictions
Applicant’s election of Group I without traverse in the reply filed on 4/28/2026 is acknowledged. Claims 271-284 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected method of use.
Applicant’s election of the following below without traverse in the reply filed on 4/28/2026 is acknowledged.
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Compound 1 is as follows:
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Examiner notes that an interview summary was held with a previous Examiner and most of the elections that were agreed upon with the Applicant were not discussed with the current Examiner. The Examiner has examined the claims under good faith to what she understands to be the agreement between the Applicant and previous Examiner.
Claims 249-270 were examined upon their merits.
No anticipatory art was found on the elected species. However, the elected species is rejected using an obviousness-type rejection. See 103 analysis below.
Claim Objections
Claim 257 are objected to because of the following informalities: the terms “NTD,” “SPRY,” “Jsol” and “Bsol” are an abbreviation and needs to be defined in the claim. Appropriate correction is required.
Claim Interpretation
Claims 250, 260, and 263-264 have product by process language and are interpreted in light of MPEP 2113(I). See 103 rejection for more details on each individual claim. “[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process.” In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985)
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 261, 263, and 270 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
The claims reference Tables 3-5 in the Specification for a 3D conformation. The claims cannot reference material in the Specification. The claims must be complete in themselves. Incorporation by reference to a specific figure or table “is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience.” Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993). See MPEP 2173.05(s).
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 249-270 are rejected under 35 U.S.C. 103 as being unpatentable over Liu, Z. et al. ( Biol Chem. 2005 Sep 11;280(45):37941–37947; “Liu”) in further view of Yan, J. et al. (WO2013156505A1; “Yan”) and Marks, A. et al. (WO2015014666A1; “Marks”).
Liu teaches RyR2 functions as a calcium release channel in the heart (Introduction, para. 2). Liu also teaches an example of RyR2 proteins in vitreous ice applied to a cryoelectron micrograph grid (Figure 3), as required by instant claims 249-250. Liu teaches the RyR2 protein in the presence of buffer (Experimental procedures, Cryo-EM para.) and Ca2+ ions in order to study its binding activity (Fig 2a, and Results para. 3), as required by instant claims 251-253. Liu also teaches there are 34 mutations in RyR2, including R2474S, that have been linked to catecholaminergic polymorphic ventricular tachycardia (CPVT), as required by instant claims 254-258. (Introduction, para. 2, lines 9-10 and para. 3. Line 2.)
Liu fails to teach a composition of a RyR2 protein with the synthetic compound of the elected specie.
Yan teaches the synthetic compound of the elected specie, as required by instant claims 249, and 266-270, as a compound for use in treat disorders and diseases associated with ryanodine receptors (RyRs) that regulate calcium channel functioning in cells. Yan also teaches the addition of ATP in an example studying the binding of calstabin to RyR2, as required by instant claims 259-265 (Example 2).
Marks also teaches the synthetic compound of the elected specie (Claim 1), however Marks teaches it as a stabilizer of RyR1 and calstabin.
Both Yan and Marks fail to teach a composition of the compound in a solution suspended in vitreous ice, as required by independent claim 249.
However, it would be obvious to a person skilled in the art to create a solution of an RyR2 protein and a compound known to modulate RyR2 and its ability to regulate Ca2+ and bind with other compounds. It would then be obvious to suspend the solution, along with Ca2+ and a buffering agent as well as any other compounds involved in the biological reaction, in vitreous ice in order to study the interaction and reactions using electron microscopy. Therefore, claims 249-270 are taught by the combined teachings of Liu, Yan, and Marks.
With respect to claims 250, 260, and 263-264, the claims are considered to have product by process language, as discussed in the claim interpretation section above. For example, claim 250 includes the language “wherein the composition is prepared by a process,” claim 260 includes the language “wherein the nucleoside- containing molecule and the synthetic compound bind a RYR domain of the protein,” and claims 263-264 include the language “wherein the ATP molecule forms a pi-stacking interaction with the synthetic compound,” which are considered product by process language. Therefore, in light of MPEP 2113(I), these limitations do not give weight to the patentability of the product of the claim and only the product is examined, and thereby rejected, as discussed in the above 103 rejection. Further, to satisfy an intended use limitation which is limiting, a prior art structure which is capable of performing the intended use as recited in the preamble meets the claim. If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction. Shoes by Firebug LLC v. Stride Rite Children’s Grp., LLC, 962 F.3d 1362, 2020 USPQ2d 10701 (Fed. Cir. 2020). See MPEP 2111.02(II).
The Supreme Court in KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007) identified a number of rationales to support a conclusion of obviousness which are consistent with the proper "functional approach" to the determination of obviousness as laid down in Graham.
Examples of rationales that may support a conclusion of obviousness include:
(A) Combining prior art elements according to known methods to yield predictable results;
(B) Simple substitution of one known element for another to obtain predictable results;
(C) Use of known technique to improve similar devices (methods, or products) in the same way;
(D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results;
(E) "Obvious to try" – choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success;
(F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art;
(G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.
Applying KSR example rationale (A), it would have been prima facie obvious create a solution of an RyR2 protein, as taught by Liu, and a compound known to modulate RyR2 and its ability to regulate Ca2+ and bind with other compounds, as taught by Yan and Marks. It would then be obvious to suspend the solution, along with Ca2+ and a buffering agent as well as any other compounds involved in the biological reaction, in vitreous ice, as taught by Liu, in order to study the interaction and reactions using electron microscopy. Therefore, claims 249-270 would be considered obvious to a person skilled in the art at the time.
Conclusion
Claims 249-270 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NICOLA MARIA BAUER whose telephone number is (703)756-1269. The examiner can normally be reached Monday-Friday 7:30-5 EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Clint Brooks can be reached at (571) 270-7682. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/N.M.B./Examiner, Art Unit 1621
/CLINTON A BROOKS/Supervisory Patent Examiner, Art Unit 1621
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