DETAILED ACTION
This Action is in response to the communication filed on 11/04/2025.
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 1, 7, 12-13, 22-24, 26, 28-38, 44, 48-50 are pending.
Claims 30-38, 44 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention and claims 22-23 are withdrawn from further consideration as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 01/17/2025 and 04/09/2025.
Claims 1, 7, 12-13, 24, 26, 28-29, 48-50 are examined herein as they read on the elected subject matter.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency – Nucleotide and/or amino acid sequences appearing in the drawings (e.g., see Figure 15) are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). Sequence identifiers for nucleotide and/or amino acid sequences must appear either in the drawings or in the Brief Description of the Drawings.
Required response – Applicant must provide:
Replacement and annotated drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers;
AND/OR
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers into the Brief Description of the Drawings, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Response to Arguments
Applicant's arguments filed 11/04/2025 have been fully considered but they are not persuasive. Applicant contends that the sequence shown in the figures are merely partial fragments of sequences already defined and numbered in the Sequence Listing.
This is not persuasive because although the sequences at issue are partial sequences of sequences already assigned SEQ ID numbers, 37 CFR 1.821(c) states:
(c) Patent applications that contain disclosures of nucleotide and/or amino acid sequences, as defined in paragraph (a) of this section, must contain a "Sequence Listing," which is a separate part of the specification containing each of those nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of §§ 1.822 and 1.823. (Emphasis added for clarity).
Therefore, each of the nucleotide sequences explicitly disclosed must be presented in the Sequence Listing using the required format. It is noted that 37 CFR 1.823(a)(5) states:
(5) Assign a separate sequence identifier to each sequence, beginning with 1 and increasing sequentially by integers, and include the sequence identifier in numeric identifier <210>. (Emphasis added).
Claim Rejections - 35 USC § 112(a) – Written Description
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 1, 7, 12-13, 24, 26, 28-29, 48-50 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.
The fundamental factual inquiry is whether the specification conveys with reasonable clarity to those skilled in the art that, as of the filing date sought, applicant was in possession of the invention as now claimed. See, e.g., Vas-Cath, Inc., 935 F.2d at 1563-64, 19 USPQ2d at 1117.
To satisfy the written description requirement, MPEP §2163 states, in part “…a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention.” Moreover, the written description requirement for a genus may be satisfied through sufficient description of a representative number of species by “…disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between functional and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus.”
The claims are drawn to a method wherein the broad claims encompass using an antagonist of CaMKII-δ9 wherein the antagonist of CaMKII-δ9 can be any antibody that specifically recognizes CaMKII-δ9, any RNAi molecule that targets an encoding sequence of CaMKII-δ9, or any antisense nucleotide that targets an encoding sequence of CaMKII-δ9 (see claim 1), with dependent claims narrowing the scope of the antagonist of CaMKII-δ9 to: an antagonist for inhibiting the phosphorylation of ubiquitin-conjugating enzyme 2T at Ser110, or a specific antagonist of CaMKII-δ9, or an antagonist that inhibits the level or activity of CaMKII-δ9 but does not significantly inhibit the level or activity of CaMKII-δ2 or CaMKII-δ3 (claims 7, 49); wherein the antibody is a monoclonal antibody or a polyclonal antibody; or wherein the antibody is a humanized antibody, a chimeric antibody or a fully human antibody, or wherein the antibody binds to the amino acid sequence encoded by exon 16 of CaMKII-δ gene; or wherein the RNAi molecule is a small interfering RNA (siRNA), a small hairpin RNA (shRNA) or a microRNA (miRNA); or wherein the RNAi molecule has 10-100 bases; or wherein the antisense nucleotide is modified to improve its stability; or wherein the RNAi molecule and the antisense nucleotide bind to exon 16 of CaMKII-δ gene; or wherein the RNAi molecule and the antisense nucleotide binds to exon 13 and exon 16 of CaMKII-δ gene, or exon 16 and exon 17 of CaMKII-δ gene, or exon 13 and exon 16 and exon 17 of CaMKII-δ gene; or wherein the agent that competes with CaMKII-δ9 to bind to its substrate is a vector that expresses CaMKII-δ9 which is without phosphorylation or oxidation function (clam 13); wherein the antibody is an antibody that specifically binds to the amino acid sequence encoded by exon 16 of CaMKII-δ9, or the antagonist is an RNAi molecule or antisense nucleotide that binds to exon 13, exon 16, and/or exon 17 of the CaMKII-δ9 gene (claim 50).
It is noted that the elected species is an RNAi molecule that targets a sequence encoding CamKII-δ9.
Accordingly, the claims encompass a genus of CaMKII-δ9 antagonists that includes a vast number of structurally and functionally distinct molecules including antibodies, small molecules, RNAi molecules, antisense nucleotides, agents that compete with CaMKII-δ9 to bind to its substrate, etc.
The application discloses two specific CaMKII-δ9 inhibitors: an shRNA (SEQ 37; see paragraph [0213] and one siRNA (that targets SEQ ID NO: 89 see [0242] in Table 3) both of which target exon 16 of CaMKII-δ9. To be clear, the specification does not appear to disclose any other specific CaMKII-δ9 inhibitors – no antibodies, no small molecules, nor any other non-siRNA/antisense molecule.
It is noted that a post-filing reference (Zhang et al. Circulation, vol. 145, no. 15 (2022)) teaches “To date, there is no drug targeting CaMKII for the clinical therapy of heart disease. Furthermore, at present, there is no selective inhibitor of CaMKII-δ, the major CaMKII isoform in the heart.” (see abstract).
Regarding RNAi inhibitors, the prior art clearly indicates that, in general, significant variability exists with regard to the functionality of individual RNAis targeting the same gene. For example, Harborth et al. (2001) J. Cell Science 114:4557-4565, in a study of siRNA mediated knockdown of different genes in cultured mammalian cells, state (page 4563) that, “For vimentin and T antigen we found that the first RNA duplex tested was ineffective, yet already the second duplex directed against a different region of the target resulted in gene silencing.” “Inspection of the sequences of the ineffective siRNA duplexes did not reveal any unusual feature.” “Currently we do not know whether the occasional ineffectiveness of an RNAi duplex arises from a local secondary structure of the mRNA, protection of the mRNA by a binding protein, or an as yet unidentified feature in the sequence of the duplex.”
Similarly, Holen et al. (2002) Nucleic Acids Res. 30:1757–1766 tested several siRNAs corresponding to different target sequences in human coagulation trigger tissue factor (hTF) for their ability to induce silencing of the hTF gene. Of the several siRNAs synthesized and tested only a few produced significant reduction in expression of hTF, suggesting that accessible siRNA target sites may be rare in some human mRNAs. Moreover, siRNAs targeting different sites in hTF demonstrated dramatic differences in silencing potency. Although strong positional effects were observed and regions of high GC content seem to be targeted less efficiently than those of low GC content, Holen et al. concluded that the factors determining the differences in siRNA efficiency remain unclear and that susceptible RNAi target sites in some genes may be rare.
The results of Holen et al. suggest that it is difficult to predict a priori what sequences to target in a gene with siRNAs to induce efficient silencing by RNAi. It was also known in the art that siRNA efficacy is highly dependent upon target position. For example, two siRNAs that target the same RNA, but that are shifted even one nucleotide in either direction can have a dramatic effect on the silencing effect of the iRNA agent. This view is expressed in Boese et al., "Mechanical Insights Aid Computational Short Interfering RNA Design," Methods in Enzymology 392:73-96, 2005; and Reynolds et al., "Rational siRNA design for RNA interference," Nature Biotechnology 22:326-330, 2004.
Accordingly, the prior art indicates that researchers must empirically determine which siRNAs molecules encompassed by the claims actually function as intended by the claims.
Therefore, in view of the vast genus of inhibitor molecules encompassed by the claims and the unpredictability taught in the prior art, the limited disclosure of the specification does not adequately describe the entire genus of inhibitor encompassed by the claims
“Possession may not be shown by merely describing how to obtain possession of members of the claimed genus or how to identify their common structural features.” Ex parte Kubin, 83 USPQ2d 1410, 1417 (Bd. Pat. App. & Int. 2007) citing University of Rochester, 358 F.3d at 927, 69 USPQ2d at 1895. Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states that “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed.” (See page 1117.) The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116).
Further, for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim. In Regents of the University of California v. Eli Lilly & Co., the court stated:
“A written description of an invention involving a chemical genus, like a description of a chemical species, 'requires a precise definition, such as by structure, formula, [or] chemical name,' of the claimed subject matter sufficient to distinguish it from other materials. Fiers, 984 F.2d at 1171, 25 USPQ2d at 1606; In re Smythe, 480 F.2d 1376, 1383, 178 USPQ 279, 284-85 (CCPA 1973) ("In other cases, particularly but not necessarily, chemical cases, where there is unpredictability in performance of certain species or subcombinations other than those specifically enumerated, one skilled in the art may be found not to have been placed in possession of a genus. . . ."). Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
The MPEP further states that if a biomolecule is described only by a functional characteristic, without any disclosed correlation between function and structure of the sequence, it is “not sufficient characteristic for written description purposes, even when accompanied by a method of obtaining the claimed sequence.” MPEP 2163. The MPEP does state that for generic claim the genus can be adequately described if the disclosure presents a sufficient number of representative species that encompass the genus. MPEP 2163. If the genus has a substantial variance, the disclosure must describe a sufficient variety of species to reflect the variation within that genus. See MPEP 2163. Although the MPEP does not define what constitute a sufficient number of representative, the Courts have indicated what do not constitute a representative number species to adequately describe a broad generic. In Gosteli, the Court determined that the disclosure of two chemical compounds within a subgenus did not describe that subgenus. In re Gosteli, 872 F.2d at 1012, 10 USPQ2d at 1618.
The court and the Board have repeatedly held (Amgen Inc. v. Chugai Pharmaceutical Co. Ltd.,18 USPQ2d 1016 (CA FC, 1991); Fiers v. Revel, 25 USPQ2d 1601 (CA FC 1993); Fiddes v. Baird, 30 USPQ2d 1481 (BPAI 1993) and Regents of the Univ. Calif. v. Eli Lilly & Co., 43 USPQ2d 1398 (CA FC, 1997)) that an adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method for isolating it, irrespective of the complexity or simplicity of the method; what is required is a description of the nucleic acid itself.
The specification discloses two specific CaMKII-δ9 inhibitors: an shRNA (SEQ ID NO: 37) and an siRNA that targets SEQ ID NO: 89. The specification provides no description or guidance that would allow one of skill to identify any other functional CaMKII-δ9 inhibitors without empirical determination. Thus one of skill at the time of the invention could not have concluded that Applicant was in possession of the genus of functional CaMKII-δ9 inhibitors that is required to practice the claimed method.
It is noted that limiting the CaMKII-δ9 inhibitors in the claims to the shRNA of SEQ ID NO: 37 and/or an siRNA that targets SEQ ID NO: 89 would obviate this rejection.
Response to Arguments
Applicant's arguments filed 11/04/2025 have been fully considered but they are not persuasive.
Applicant argues that claim 1 has been amended to limit the antagonist to an antibody that specifically recognizes CaMKII-δ9, an RNAi molecule that targets an encoding sequence of CaMKII-δ9, or an antisense molecule that targets an encoding sequence of CaMKII-δ9.
This is not persuasive because although claim 1 has been narrowed in scope, the claim now encompasses any antibody that specifically recognizes CaMKII-δ9, any RNAi molecule that targets an encoding sequence of CaMKII-δ9, or any antisense molecule that targets an encoding sequence of CaMKII-δ9 and there is insufficient written description for the genus of antibodies, RNAi molecules, and antisense molecules encompassed by the claims.
Applicant argues the specification teaches and demonstrates that the inventive contribution lies in the discovery of the biological effect of modulating CaMKII wherein inhibiting CaMKII-δ9 expression can lead to therapeutic benefit. Applicant asserts that a person of ordinary skill in the art would readily understand that any functional CaMKII-δ9 inhibitor could be used to achieve the same result and that since an antibody, RNAi molecule and antisense nucleotide encompassed by the claims are known in the art (citing references for support of specific antibodies, RNAi and antisense molecules) it should not be required to exhaustively list every possible antibody, RNAi molecule or antisense nucleotide encompassed by the claims.
This is not persuasive because, as indicated above, the court and the Board have repeatedly held that an adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method for isolating it, irrespective of the complexity or simplicity of the method; what is required is a description of the nucleic acid itself. Furthermore, there is no identification of a core structure common to all members of each genus that would allow one of skill in the art to readily identify any non-disclosed members which have the required function. Furthermore, as previously indicated and reiterated in the rejection above, Zhang et al. (2022) teaches “To date, there is no drug targeting CaMKII for the clinical therapy of heart disease. Furthermore, at present, there is no selective inhibitor of CaMKII-δ, the major CaMKII isoform in the heart.” (see abstract). It is also noted that the references Applicant cites for support of known antibodies, RNAi molecules and antisense nucleotides are references filed after the earliest claimed priority date of the claimed invention, 06/18/2019. Thus, the references do not demonstrate that Applicant had possession of the antagonists taught in the cited references, let alone the broader genus of antagonists encompassed by the claims, at the time the invention was filed.
Applicant argues that the experimental data demonstrates to one skilled in the art that Applicants were in possession of the claimed invention.
This is not persuasive because, as indicated in the rejection, the only experimental data provided by the specification only demonstrates two specific CaMKII-δ9 inhibitors: an shRNA (SEQ ID NO: 37; see paragraph [0213]) and one siRNA (that targets SEQ ID NO: 89 see [0242] in Table 3) both of which target exon 16 of CaMKII-δ9. It is noted that limiting the claims to either of these two specific inhibitors would obviate the rejection.
Therefore, with respect to the rejection of claims under 35 USC 112(a) (written description), Applicant’s arguments are not persuasive.
With respect to the rejection of claims under 35 USC 112(b) as set forth in the previous Office Action, Applicant’s arguments, see filed 11/04/2025 have been fully considered and in view of the amendment to the claims are persuasive. The rejection(s) has(have) been withdrawn.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to J. E. Angell whose telephone number is (571)272-0756. The examiner can normally be reached Monday-Friday (8:30-5:00).
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jennifer Dunston can be reached at (571) 272-2916. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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J. E. Angell
Primary Examiner
Art Unit 1637
/J. E. ANGELL/ Primary Examiner, Art Unit 1637