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 .
Claim Interpretation
For the purposes of this examination the protein phosphatase inhibitor-1 or “I-1” as recited in the claims is interpreted to encompass both the endogenous wild-type inhibitor-1 and the engineered constitutively active variants thereof, including I-1c. This interpretation is supported by [0076] of the specification.
Claim Objections
Claim 135 is missing space between “1” and “minute;” and “about” and “5”, in subsection (b) and (c).
Claim 140 appears to be free of rejection and may be allowable if written in an independent form.
Election/Restrictions
Applicant’s election without traverse of Group I drawn to a method of treating a patient having a heart failure using an rAAV in the reply filed on 12/10/2025 is acknowledged. Claims 124-145 are pending and under exam. Claims 146-151 are withdrawn.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on May 30, 2025 and Mar 06, 2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Election/Restrictions
Applicant’s election without traverse of Group I drawn to drawn to a method of treating a patient having a heart failure using an rAAV in the reply filed on Dec 10, 2025 is acknowledged. Claims 129-145 are pending and under exam. Claims 146-151 are withdrawn.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 129-145 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement.
The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Regarding claim 129: The specification does not demonstrate possession of full scope of the claimed invention. The specification provides support for manufacturing and stably expressing the I-1 gene in viral rAAV vectors. (See Example 4). However, instant specification only demonstrated treatment of heart failure using I-1c gene. (See Examples 5-7). It is noted that methods of manufacturing cannot be equivalent to the methods of treatment or therapeutic efficacy. It is also noted that as evidenced by Carr I-1 is structurally distinct from I-1c, as I-1c is the constitutively active form. (See Carr abstract, See PTO-892).
In view of the above, it is submitted that Applicants were not in possession of the full scope of the claimed invention at the time of filing of the instant invention.
Regarding claim 139: section b of claim 139 requires 85% sequence identity to amino acid residues 1-54 of SEQ ID NO: 1. This claimed composition encompasses all vectors polypeptides comprising >85% identity to amino acid residues 1-54 of SEQ ID NO: 1.
Applicant’s claims do not provide support for all nucleic acids comprising 85% identity to amino acid residues 1-54 of SEQ ID NO: 1. The specification as filed does not provide sufficient evidence that Applicants were in possession of the full scope of the claimed invention at the time of filing of the instant invention. As such, >85% identity to a 54 amino acid polypeptide, encompasses
54
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8
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×
19
8
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t
h
a
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1.7
×
10
19
polypeptides if only substitution mutations were considered (i.e., excluding deletions or insertions). This amounts to enormous number of polynucleotides which do not have support in the specification, The specification also does not provide any guidance on how or where the amino acids can/need to be changed in order to arrive at the claimed composition. It is clear that the vector of the invention was restricted to SEQ ID NO: 1 or amino acid 1-54 of SEQ ID NO: 1. For example, see instant specification at [0063], [0086] and [0107].
Thus, Applicants were not in possession of the full scope of the claimed invention at the time of filing of the instant invention.
It is also noted that similar analyses apply for claim 141 (d).
Regarding claim 141: The claim requires replacement of T at position 35 with any amino acid that is not T or other synonymous amino acids. However, the specification did not show treatment of heart failure with any of the 18 remaining amino acids. The specification indicated that “failing human cardiomyocytes expressing I-1T35D exhibit normal contractile function under basal conditions and their beta adrenergic function is restored to normal.” (See spec at [0312]). However, the specification did not explicitly show or teach treatment of heart failure using any other amino acid substitution except aspartate at position 35. It is clear that the treatment of cardiac symptoms was restricted to T35D mutant. As such the scope of the claim far exceeds the disclosure in the specification.
Thus, Applicants were not in possession of the full scope of the claimed invention at the time of filing of the instant invention.
Claims 130-145 are rejected for their dependencies on the rejected claims.
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 129, 130, 133-134, 139, and 143-144 rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as failing to set forth 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.
Claim 129 requires a patient having classification of congestive heart failure. However, the specification fails to provide any parameters or guidance regarding how to identify a patient having such a classification. In particular it is submitted that it is unclear which of the numerous classification systems is required to meet the limitation and how much improvement requires a patient to no longer be classified as a CHF patient. Appropriate clarification is required.
Claims 133-134, and 144 require improvement in the at least one parameter from a baseline level in the patient. However, it is not clear from the specification as to what value constitutes a baseline. The specification also does not provide any guidance to determine the baseline level for each of the indicated parameters. As such the metes and bounds of the claim is indefinite.
Claim 143 recites types of Limb-girdle muscular dystrophy, Glycogen storage diseases and progressive familial heart block in parenthesis. The metes and bounds of this phrase are indefinite since it is unclear how these limitations relate to the scope of the claimed invention.
Claim 139 recites the limitation "I-1c" in line 1. There is insufficient antecedent basis for this limitation in the claim.
Claim 130 and 144 contain the trademark/trade name Minnesota LIVING WITH HEART FAILURE® Questionaire. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe Minnesota LIVING WITH HEART FAILURE® Questionaire and, accordingly, the identification/description is indefinite.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 129, 131, 133-134, 136-139, 142 and 144-145 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ishikawa et al (Mol Ther. 2014 Dec; hereinafter "Ishikawa;" See IDS filed Mar 06, 2025) ; further as evidenced by various references cited herein.
Regarding claim 129, 131, 133-134, 138-139, and 141-144: Ishikawa was directed to use of a novel cardiotropic vector generated by capsid reengineering of adeno-associated virus (BNP116) to improve cardiac function in chronic HF by overexpressing constitutively active inhibitor-1 (I-1c) (as required by claim 139). (See Ishikawa Abstract). Ishikawa used 1.0 × 1013 vector genomes (vg) of the rAAV (as required by claims 129 and 138) one month after a large anterior myocardial infarction and observed that the mean left ventricular ejection fraction (as required by claim 133) increased by 5.7% in the high-dose group, and by 5.2% in the low-dose group (as required by claim 134), whereas it decreased by 7% in the saline group, 2 months post administration. As such, Ishikawa taught treatment of a patient having heart failure by administering at least one dose of rAAV vector comprising a nucleic acid encoding I-1 wherein at least one dose of the rAAV is selected from a total dose-range of about 1013 vg.
It is noted that Ishikawa did not teach or disclose at least twelve months post-administration there is an improvement in the classification of congestive heart failure, or an improvement in the classification of at least one level within 6 or 12 months after administration of the rAAV as required by claim 131 or 144. It is however noted that a whereby/wherein clause in a method claim “is not given weight when it simply expresses the intended result of a process step positively recited” (MPEP 2111.04). As discussed above, Ishikawa teaches the method of treating a patient having a heart failure, comprising: administering into heart cells of the patient having a classification of congestive heart failure (CHF), at least one total dose of a rAAV vector comprising a nucleic acid sequence encoding a phosphatase inhibitor (I-1) protein that inhibits phosphatase activity, wherein, at least one dose of the rAAV is selected from a total dose-range of about 1013 vg to about 1015 vg, thus the method disclosed by Ishikawa would necessarily result an improvement in the classification of congestive heart failure at least twelve months post-administration.
Regarding claim 136 and 137: Ishikawa disclosed that “BNP116 was developed as a chimera of AAV-2/AAV-8, which readily traverses the blood vasculature and selectively transduces cardiac and whole-body skeletal muscle tissues with high efficiency while detargeting the liver and the lungs.” (See Ishikawa p.2039, col. 1, para 1).
Regarding claim 141: Ishikawa disclosed that “The rationale (sic) for overexpressing I-1c is that it is truncated to 65 amino acids from 171 and lacks other phosphorylation sites that negatively impact cardiac function. In addition, Thr 35 is replaced by phosphomimetic aspartic acid (T35D) and takes constitutively active form, thus leading to decreased PP-1 activity.” (See Ishikawa p.2040, col 1-2)
Regarding claim 142-143: Ishikawa “demonstrated that BNP116.I-1c gene transfer improves cardiac function and possibly prevents post-MI LV dilatation in a well-established model of chronic ischemic cardiomyopathy.” (See Ishikawa p.2039, col. 2, para 4). It is further known that several congenital hear issues such as congenital heart block can give raise to “[c]ardiac manifestations reported include dilated cardiomyopathy, endocardial fibroelastosis and mitral insufficiency.” (See evidence in Jayaprasad et al; Int J Cardiol. 2006 Sep 20; Abstract, See PTO-892)
Regarding claim 145: Ishikawa referred to Ishikawa et al (J Vis Exp. 2011 May 15; hereinafter “Ishikawa-II” See PTO-892) for a method of administration of virus. Ishikawa-II used nitroglycerin following viral infusion. (See Ishikawa-II; p. 2, #4) It is noted that nitroglycerin is a vasodilator. (See evidence in Kim et al; Nitroglycerin. 2023 Jul 31; See PTO-892; first para).
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 130, 132 and 135 are rejected under 35 U.S.C. 103 as being unpatentable over Ishikawa et al (Mol Ther. 2014 Dec; hereinafter "Ishikawa;" See IDS filed Mar 06, 2025) and cited evidentiary references above, in view of Yee et al (; hereinafter “Yee;” See PTO-892).
Regarding claims 130 and 132: The teachings of Ishikawa are set forth above. Ishikawa did not teach or suggest classification system used by the American Heart Association (AHA), the American College of Cardiology (ACC), Minnesota LIVING WITH HEART FAILURE@ Questionnaire (MLHFQ), Kansas City Cardiomyopathy questionnaire (KCCQ), or the 2016 European Society of Cardiology guidelines (ESCO), the Japanese heart failure Society (JHFS) guidelines, The Japanese Circulation Society (JCS) Guidelines, or, the New York Heart Association (NYHA) as required by the claim. Yee taught that “[t]he Kansas City Cardiomyopathy Questionnaire (KCCQ) and the Minnesota Living with Heart Failure Questionnaire (MLHFQ) are the 2 most widely adopted patient reported outcome measures specific to HF.” (See Yee Abstract). It is further noted that “The KCCQ is a 23-item self-administered questionnaire that quantifies multiple domains of patients’ HF-related health status including physical limitation, symptom stability, symptom frequency, symptom burden, self-efficacy, quality of life, and social limitations. Items are scored from 0 to 100 with 0 representing the worst and 100 the best possible functional status.” (See Yee p. 2, last para). While Yee did not explicitly teach “KCCQ fair to excellent scores of 50 to 100, very poor to fair scores of 0 to 49, good to excellent scores of 75 to 100, and very poor to good scores of 0 to 74” as required by claim 132, it is submitted that choosing cutoffs to define severity strata is routine and obvious. It is indicated that selecting thresholds within a known continuous scale is routine optimization, absent unexpected results tied to a specific cut off. (See MPEP 2144).
Regarding claim 135: The teachings of Ishikawa are set forth above. It is noted that Ishikawa did not teach or suggest any of the claimed methods of administration. However varying infusion duration or dividing a total dose into multiple sub doses administered sequentially over a defined period of time represents routine optimization parameters such as infusion rates, total infusion time and dosing schedule, which are result-effective variables in viral vector delivery as set forth in MPEP 2144. It would have been obvious for a person of ordinary skill in the art to adjust the rate or dose of administration of the therapeutic to a longer or shorter period or divide into multiple sub doses. Applicant has not demonstrated criticality of the doses or regimens to produce any unexpected results. Accordingly, it is submitted that the claimed method is obvious.
Conclusion
Claim 140 appears free of art in view of sequence search results. No prior art appears to render claim 140 obvious or unpatentable in view of sequence search results.
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JAGAMYA VIJAYARAGHAVAN whose telephone number is (703)756-5934. The examiner can normally be reached 9:00a-5:00p.
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/JAGAMYA NMN VIJAYARAGHAVAN/ Examiner, Art Unit 1633
/EVELYN Y PYLA/Primary Examiner, Art Unit 1633