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 .
DETAILED ACTION
The amendment to the claims filed after non-final office action on March 9, 2026 is acknowledged. Claims 1, 4-5, 10, 20 were amended, claims 2-3, 6-9, 14-19 were canceled, claims 21-25 were newly added and claims 1, 4-5, 10-13, 20-25 are pending in the instant application. The restriction was deemed proper and made final previous office action.
Claims 10-13, 23-25 are withdrawn as being drawn to a non-elected species/invention. Claims 1, 4-5, 20-22 are examined on the merits of this office action.
Withdrawn Rejections/Objections
The objections to claims 6, 17-18 are hereby withdrawn in view of amendment of the claims filed March 9, 2026.
The objection to the specification is withdrawn in view of amendment of the specification filed March 9, 2026.
The rejection of claims 1, 4-6, 17-20 under 35 U.S.C. 112, first paragraph, as failing to comply with the written description requirement (new matter) is withdrawn in view of amendment of the claims filed March 9, 2026.
The rejection of claims 1, 4-7, 9, 15, 17-20 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 rejection of claims 1, 4-7, 17-20 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112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement is withdrawn in view of amendment of the claims filed March 9, 2026. However, please note that new claims 21-22 are subject to the written description rejection and is presented below.
The rejection of claims 4, 6, 18 under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends is withdrawn in view of amendment of the claims filed March 9, 2026. .
New Rejections
Claim Rejections - 35 USC § 112, First Paragraph
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 21-22 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
MPEP § 2163 states that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, or 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 function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus.
Scope of the claims
The CCP-related claims are directed to methods for promoting formation of a cyclic peptide by introducing complementary “dimer zipper fastener parts” at the termini of a peptide comprising a cyclic citrullinated peptide (CCP) linear amino acid sequence. The claims are not limited to a specific amino acid sequence, a particular citrullination site, a specific peptide length, or any identified CCP epitope. Instead, the claims broadly recite a “CCP linear amino acid sequence” positioned between the terminal zipper motifs. The claims encompass a potentially large genus of citrullinated peptide sequences. A person of ordinary skill in the art (POSITA) would recognize that numerous citrullinated peptide antigens have been used in rheumatoid arthritis diagnostics and that CCP is not a single universally defined amino acid sequence. Nevertheless, the claims do not require citrullinated peptide antigens that have been used in rheumatoid arthritis diagnostics. Consequently, the claims appear to extend beyond any particular CCP peptide and instead cover a broad class of citrullinated peptide sequences modified with the claimed zipper motifs.
Actual Reduction to Practice
MPEP § 2163 states that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice. A “representative number of species” means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.
The specification contains experimental examples involving a “zipper fastener type CCP cyclic peptide” and presents ELISA data comparing the claimed construct with a conventional CCP cyclic peptide. These examples suggest that the inventors reduced at least one CCP embodiment practice. However, the specification never identifies the amino acid sequence of the CCP peptide used in those experiments. No SEQ ID NO or sequence is provided. No peptide length is disclosed. No citrullination sites are identified. No structural description of the CCP peptide use din the examples is provided. Accordingly, while the specification suggests possession of at least on CCP-based construct, it does not disclose the identify of the CCP sequence that was allegedly reduced to practice. The disclosure therefore demonstrates possession of an undisclosed species.
Therefore, the instant specification has failed to meet the written description requirement by actual reduction to practice of a representative number of species alone.
Sufficient relevant identifying characteristic
MPEP § 2163 states that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, or 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 function and structure, or by a combination thereof.
The specification refers to “CCP peptide”, CCP linear amino acid sequence and cyclic citrullinated peptide but does not provide amino acid sequences, consensus motifs, sequence length, citrullination patterns or representative CCP species. The term “CCP” is used as a label rather than as a structural description. While a person of ordinary skill in the art may understand generally that CCP peptides are citrullinated peptide antigens used in rheumatoid arthritis diagnostics, the specification does not identify what structural feature distinguish the claimed CCP sequences from the potentially numerous citrullinated peptides known in the art. Accordingly, the disclosure fails to provide sufficient identifying characteristics of the claimed CCP genus.
Physical/Chemical Properties
The specification contains little or no discussion regarding physical or chemical properties of the claimed CCP sequence genus. The disclosures does not address peptide length, molecular size, flexibility, spacing between terminal zipper motifs required, steric constraints, cyclization tendencies and aggregation behavior across different CCP sequences. The specification explains the properties of the zipper motifs themselves, including electrostatic interaction and disulfide bond formation through cysteine residues. However, those discussions concern the zipper portions of the construct rather than the CCP sequence genus recited in the claims. The absence of any meaningful discussion regarding physical or chemical properties of the CCP sequence genus weighs against a finding that the inventors possessed the full scope of the claimed subject matter.
Functional characteristics when coupled with a known or disclosed correlation between function and structure:
The specification reports functional results showing that a zipper modified CCP peptide exhibited diagnostic activity in ELISA testing. However, the disclosure does not establish a correlation between CCP sequence structure and successful operation of the claimed invention. Specifically, the specification does not disclose which CCP sequence was used, why that sequence was selected, whether other CCP sequences were tested and what structural features are required for successful cyclization. The inventors therefore provide functional data for an unidentified species without teaching why the results would extend across the full breadth of the claimed genus. This deficiency is particularly significant because CCP peptides are not necessarily interchangeable. Peptide length, citrullination position, amino acid composition and conformational constraints may all effect cyclization efficiency, zipper interaction, antigen presentation and assay performance. Without disclosure of a structure function relationship applicable across the claimed genus, the specification does not reasonably convey possession of all CCP sequences encompassed by the claims.
Method of Making
The specification generally teaches attaching zipper motifs such as KKCK and DCDD to a CCP peptide sequence. However, the disclosure assumes the existence of a CPP peptide and does not teach how to identify, select or define members of the claimed CCP sequence genus. The specification therefore teaches how to modify a CCP peptide once selected but does not teach what CCP sequences are encompassed by the claims. A method of attaching terminal zipper motifs does not itself proved written description support for the entire genus of CCP sequences to which those motifs may be attached.
Conclusion
The specification appears to demonstrate possession of at most a single CCP embodiment. Even that embodiment is not structurally disclosed because the underlying CCP amino acid sequence is never identified. The claims broadly recite a “cyclic citrullinated peptide (CCP) linear amino acid sequence” without limitation to any specific sequence, epitope, length or structural class. As drafted, the claims potentially encompass numerous distinct citrullinated peptide sequences known in the rheumatoid arthritis field. The specification does not disclose representative species, common structural features, relevant identifying characteristics, physical or chemical properties, or a structure function correlation sufficient to demonstrate possession of that broad genus. Instead, it merely references “CCP” generically while presenting experimental results for an unidentified peptide. The specification fails to reasonably convey to a person of ordinary skill int eh art that the inventors were in possession of the full scope of the claimed CCP genus.
Response to Applicant’s Arguments
Applicant argues newly added claim 21 supports written description..
Applicant recites a cyclic peptide formation method in newly added independent claim 21, which recites the formation of a cyclic peptide by introducing dimer zipper fastener parts into the N- terminus and C-terminus of a CCP linear amino acid sequence (the only cyclic peptide embodiment disclosed in the specification). New Claim 21 therefore relates to embodiments specifically disclosed in the specification. Withdrawal of the rejection as to Claim 21 is respectfully requested.
Please also note that the specification provides proper written description support for the amended claims. Support for the CCP cyclic peptide (Newly added claim 21 and 22): The specification explicitly discloses the technical solution of forming a cyclic peptide by introducing zipper fastener parts into the CCP linear amino acid sequence:The specification clearly states that the cyclic peptide comprises a CCP linear amino acid sequence, with dimer zipper fastener parts introduced into its N-terminus and C-terminus respectively (see Example 2), and the optimal integral structure of the cyclic peptide is KKCK-CCP linear amino acid sequence-DCDD (see Example 2).
The specification verifies the improved detection sensitivity of the CCP cyclic peptide modified with zipper fastener parts through specific examples (see Example 2), also achieving actual reduction to practice of the technical solution.
Applicant’s arguments have been fully considered but not found persuasive. Although Applicant contends that newly added claim 21 is directed to the only cyclic peptide embodiment disclosed in the specification and the Example 2 demonstrates actual reduction to practice, the specification does not identify the amino acid sequence of the CCP linear amino acid sequence used in the disclosed embodiment. The claims broadly recite “a CCP linear amino acid sequence” without limiting the claimed subject matter to any particular CCP sequence. The specification further fails to disclose representative CCP species, common structural features, or other identifying characteristics sufficient to reasonably convey to a person of ordinary skill in the art that Applicant was in possession of the full scope of the claimed CCP genus at the time of filing. Accordingly, the written description rejection is maintained (see above rejection).
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 1, 4-5, 20 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.
Claim 1 was amended to recite the phrase “the protein dimer by the ESAT6 and CFP10” renders the scope of the claimed protein dimer unclear because it is not reasonably certain whether the claimed dimer is a heterodimer comprising ESAT6 and CFP10, a homodimer of either or another dimeric complex involving the recited proteins. Accordingly the metes and bounds of the claim cannot be determined with reasonable certainty. If applicants intends the dimer to be one ESAT6 molecule associated with one CFP10 molecule (heterodimer), an amendment could be”….and the pair of dimer zipper fastener parts promote formation of a dimer, wherein the dimer is a heterodimer comprising ESAT6 and CFP10” or something similar. In its current form, it is unclear what is meant bey “promote the formation of the protein dimer BY the ESAT6 and CFP10”. Claims 4-5, 20 are also rejected due to dependence on claim 1 and not further clarifying this point of confusion.
Closest Prior Art Made of Record
Bajaj (US20200172576 A1, cited previously) teaches of A fusion polypeptide comprising a target polypeptide and a tag polypeptide, wherein the tag polypeptide is present on a N-terminal side and/or a C-terminal side of the target polypeptide and has a structure represented by Xaa-Cys-Zaa, i) Xaa being Asp or Glu, and Zaa being Asp or Glu; or ii) Xaa being Lys or Arg, and Zaa being Lys or Arg (see claim 1). Bajaj further teaches of peptide tags separately comprising KKCKK and DDCDD (see Table 3). However, Bajaj is not adding the two different tags to polypeptides and combining to form dimers. The use of the tags is solely for recovering the fusion protein and to inhibit dimer formation/aggregation and or conjugation with to labels or additional agents. In fact, Bajaj teaches improved monomer formation (independent of each other) of the peptides and suppression of aggregation (which was the goal of using the tags) (see paragraph 0067). Bajaj does not teach, suggest or provide a motivation to tag the polypeptides with the different tags (KKCKK and DDCDD) and combine to form dimeric structures. In fact, the goal was the opposite, add one of these tags to minimize aggregation when producing the peptide and also have a site of conjugation to labels or additional agents via the cysteine residue (see paragraph 0037).
Conclusion
No claims are allowed.
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 ERINNE R DABKOWSKI whose telephone number is (571)272-1829. The examiner can normally be reached Monday-Friday 7:30-5:30 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, Lianko Garyu can be reached at 571-270-7367. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/ERINNE R DABKOWSKI/Examiner, Art Unit 1654
Prosecution Insights