DETAILED ACTION
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 .
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.
Status of the Claims
Claims 63-72 and 77-91 are pending; claims 1-62 and 73-76 are canceled; claim 77 is amended; claims 63-72 are withdrawn; claims 88-91 are newly recited. Claims 77-91 are examined below.
Priority
Acknowledgment is made of the present application as a proper National Stage (371) entry of PCT Application No. PCT/US2020/066011, filed 12/18/2020, which claims benefit under 35 U.S.C. 119(e) to provisional application No. 62/949,869, filed 12/18/2019.
Information Disclosure Statement
The information disclosure statement (IDS) filed 09/16/2025 is considered, initialed and attached hereto.
Withdrawn Objections/Rejections
The previous objection to the specification (regarding Sequence Compliance) is withdrawn in response to Applicant’s amendments to the specification.
The previous rejections of claims under 35 U.S.C. 102 and 35 U.S.C. 103 citing Roberts et al. as primary reference and citing Schenk et al. as primary reference are withdrawn in response to Applicant’s amendments to the claims (the claims amended to recite
The previous rejection of claims under 35 U.S.C. 101 is withdrawn in response to Applicant’s amendments to the claims.
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 77-91 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.
Claims 77, 80, 89 and 90 each recite “each of the one or more probe molecules comprise an amino acid sequence having at least 80% identity to HWQIAYNEHQWQ (SEQ ID NO:1)”, and claim 90 recites “having at least 90% sequence identity to HWQIAYNEHQWQ (SEQ ID NO: 1)”, and as a result the claims are directed to an extremely large and potentially variable genus of probe molecule described in terms of functional ability (must be capable of preferentially binding a cardiac protein), as the probe molecule can be any polypeptide sequence containing SEQ ID NO. 1 (see the language, “probe molecules comprise an amino acid sequence”. The recited language encompasses the claimed sequences and all larger sequences which include SEQ ID NO. 1) and further includes/contain any sequence with 80% (or 90%) identity to SEQ ID NO. 1 (including sequences comprising substitutions, deletions and additions).
Additionally, claims 88 and 91 recite “having at least seven contiguous amino acids of HWQIAYNEHQWQ (SEQ ID NO: 1)”, which encompasses variations of SEQ ID NO. 1 having 5 variant residues (retaining only the middle residues, i.e., up to 5 differences on either end).
The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed. The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the application. These include: (1) Actual reduction to practice, (2) Disclosure of drawings or structural chemical formulas, (3) Sufficient relevant identifying characteristics (such as: i. Complete structure, ii. Partial structure, iii. Physical and/or chemical properties, iv. Functional characteristics when coupled with known or disclosed, and correlation between function and structure), (4) Method of making claimed invention, (5) Level of skill and knowledge in the art, and (6) Predictability in the art.
The originally filed specification provides no specific examples or reduction to practice regarding any sequences containing particular variants of SEQ ID NO. 1. There is no correlation between structure and function, for example, the originally filed specification fails to provide any direction as to what specific residues within SEQ ID NO. 1 are necessary (must be conserved) in order to achieve the desired binding encompassed by the claims (that are responsible for binding specifically cardiac protein). Applicant has not disclosed a representative number of species such to suggest any particular structure-function correlation. For example, even regarding claims 88 and 90 (limited to 7 contiguous residues without indicating which 7 residues must be conserved), the specification fails to indicate which of the middle residues of SEQ ID NO. 1 are required in order to achieve binding as claimed.
The level of skill in the art is high, however, even in the case of peptides having 80% or 90% identity to a defined peptide (such as that as claim 80), it is not within the skill of the art to predict any and all substitutions that would result in a peptide that mimic or preserve the function of SEQ ID NO. 1. The prior art recognizes that structure is not a reliable indicator of function, and even seemingly minor changes in a given structure can completely change its binding.
For example, see Harlow et al. (Harlow, E. and Lane, D., Antibodies: A Laboratory Manual (1988) Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, pages 23-26 ), who teach that the loss of a single hydrogen bond can dramatically affect the ability of an antibody to recognize a cognate antigen (see especially page 26, first full paragraph).
Lederman et al., "A single amino acid substitution in a common African allele of the CD4 molecule ablates binding of the monoclonal antibody, OKT4" Mol Immunol. 1991 Nov;28(11):1171-81, found that a single amino acid substitution on the antigen CD4 ablated binding of a monoclonal antibody (see title and abstract).
As further illustration of the unpredictability in the art, Brown et al. (“Tolerance of single, but not multiple, amino acid replacements in antibody VH CDR 2: a means of minimizing B cell wastage from somatic hypermutation?”, J Immunol. 1996 May;156(9):3285-91), describes how a one amino acid change in the VHCDR2 of a particular antibody was tolerated whereas, the antibody lost binding upon introduction of two amino changes in the same region (at 3290 and Tables 1 and 2).
See also Lucchese et al., How a single amino acid change may alter the immunological information of a peptide, Frontiers in Bioscience E4, (2012), p. 1843-1852, regarding predictability among the relationship between protein structure and function, Lucchese et al. teach even a single amino acid change in a peptide sequence can impact its function, that there is no rule available to predict/explain the functional outcomes of amino acid changes (see page 1843, col. 1, para 1). See at page 1843, col. 2, Lucchese teach the functional importance of even a single amino acid substitution is evident at both the physiological and pathological levels (see examples provided at col. 2 through page 1844). Those of ordinary skill in the art recognize that a single residue change can result in a wide spectrum of outcomes in an immunological context (page 1848, second to last paragraph at col. 1).
One having ordinary skill in the art cannot readily visualize the identities of the other members of the genus (other than the identified SEQ ID NO. 1) exhibit both the structural and functional requirements of the claim. There is no disclosed partial structure or other common structural features, common to the members of the genus, which are responsible for conferring the desired function.
For the reasons as discussed in detail above, the originally filed specification fails to provide evidence that supports Applicant was in possession of methods as claimed comprising probe molecules, other than SEQ ID NO 1., that have “sequence having at least 75% sequence identity to… (SEQ ID NO. 1)”. As a result, the claims are rejected for having insufficient written description regarding this limitation.
Response to Arguments
Applicant's arguments filed 12/01/2025 have been fully considered but they are not persuasive for the following reasons.
Regarding remarks page 9-10, see as indicated above Applicant’s updated Sequence listing is accepted and further the objection to the specification is withdrawn in response to amendments to the specification.
Applicant argues the rejection of claims under 35 U.S.C. 112(a), regarding insufficient written description (claims 11-12). Applicant refers to the amendments of the claims to recite “having at least 80% identity”, arguing that this means the polypeptide must have at least 10 amino acids in common with SEQ ID NO. 1 (or 11 out of 12 for identity at least 90%). Applicant argues that a polypeptide having 10 or 11 amino acids in common with the 12 residue peptide sequence of SEQ ID NO. 1 is well within the skill level of understanding of one skilled in the art, especially if at least 7 must be consecutive. However, this argument offers no supportive evidence that such sequences would necessarily exhibit the claimed binding/function. Specifically, there is not supportive evidence that retaining at least 10 or 11 residues, or 7 contiguous, would maintain binding, particularly when there is evidence that in a binding region, even one single changed residue could completely change binding (see for example Harlow and Lane, Lederman et al., Lucchese et al. and Brown et al., all cited in the rejection above as supporting that even a single substitution could change binding). Applicant has provided no specific evidence that supports Applicant was in possession of all other sequences encompassed by recited language other than polypeptides having SEQ ID NO. 1 itself which bind to cTnI.
Regarding remarks specific to the rejections of claims under 35 U.S.C. 101, 35 U.S.C. 102 and 35 U.S.C. 103 (remarks pages 12-15), see as indicated above, these rejections of claims are withdrawn in response to Applicant’s amendments to the claims.
For this reason, Applicant’s arguments are not persuasive.
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.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ELLEN J MARCSISIN whose telephone number is (571)272-6001. The examiner can normally be reached M-F 8:00am-4:30pm.
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/ELLEN J MARCSISIN/Primary Examiner, Art Unit 1677