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 .
Status of the Application
The amendment and remarks of 14 November 2025 are entered.
Claims 1-20 are pending and are being examined on the merits.
The rejection of claims 1 and 3-20 under 35 U.S.C. 112(a) is maintained, with the Examiner’s response found below.
The rejection of claims 2-7 under 35 U.S.C. 112(b) is withdrawn with respect to claims 3-7 owing to the amendment filed 14 November 2025, but maintained with respect to claim 2 with the Examiner’s response found below.
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 1 and 3-20 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.
At issue for claims 1 and 11 is the combination that the peptide, polypeptide must be one that specifically binds to cells of the brain and/or spinal cord, as well as that it contains a sequence XDGXXWX, where X can be any naturally occurring amino acid.
One of ordinary skill in the art can assume at a minimum that 22 amino acids read upon “naturally occurring” as claimed, although some post-filing art suggests 500 or more options for naturally occurring monomers even if only 22 are generally utilized (see e.g. Flissi et al. Nucleic Acids Research 48:D465-D469). However, pre-filing art also suggest that at least 500 naturally occurring amino acids are considered by one of ordinary skill in the art (see e.g. Wagner I and Musso H Angewandte Chemie Intl. Ed. 22:816-828, published 1983). Only assuming 22 amino acids as options for the X residues allows for 234,256 permutations that still read upon the generic sequence as claimed. Increasing to the 500 suggested by Wagner allows for 6.25*1010 permutations.
The specification guides that brain or spinal cord cell-specific sequences were derived from extensive AAV VP1 protein library screening utilizing 108 variants, resulting in 5 selected sequences (see e.g. Example 1). The highly limited sequences selected from a very large display library indicates unpredictability in determining if heptamer sequences will actually bind to cells of the brain and/or spinal cord.
The five sequences identified by the Applicants do share an XDGXXWX motif. However, the issue is that there is no clear indication that the motif is solely responsible for binding to cells of the brain and/or spinal cord. The breadth of the peptide library screened by the Applicants is sufficiently diverse that it should in theory cover every possible variant of the XDGXXWX motif, and more broadly covers nearly every possible heptamer permutation considering 22 amino acids. Should one of ordinary skill only consider 20 naturally occurring amino acids, the library would cover every single permutation, though the possible variants for XDGXXWX drops to 160,000.
The skilled artisan recognizes possession of SEQ ID NOs:2-5 having the XDGXXWX motif. However, it is not clear to the skilled artisan that the full genus of XDGXXWX having specificity for cells of the brain and/or spinal cord is possessed by the Applicants. As argued above, the genus encompasses 160,000-234,000 species. The library screening of the Applicants almost certainly covered every possible variant within that genus. Only five sequences are identified as having the claimed binding ability. One of ordinary skill in the art considering the totality of the specification and disclosed sequences would likely conclude that mere presence of an XDGXXWX motif does not guarantee binding to brain and/or spinal cord cells since only five peptides are isolated having that ability. Since only five peptides from a library of 108 were isolated, this argues that the Applicants did not actually possess a genus of peptides having the claimed motif, nor that they all bound to cells of brain and/or spinal cord.
The rejected dependent claims do not remedy this deficiency.
Response to Arguments:
The applicants summarize the rejection of record.
The Examiner finds no issues with the summary as provided.
The Applicants argue the specification includes four peptides that read upon the XDGXXWX motif as in claims 1 and 11. The Applicants argue the data in the specification allows one of ordinary skill in the art to synthesize all variants of the claimed motif that bind to brain or spinal cord cells.
The Examiner disagrees that the disclosure of 4 peptides is representative of the genus as claimed of peptides having an XDGXXWX motif as well as the ability to bind to cells of the brain or spinal cord. As argued in the rejection of record, the smallest genus assuming each of X is only one of 22 amino acids leads to 234,000 species. The largest possible genus assuming a broader 500+ naturally occurring amino acids leads to 6.25*1010 species. The identification of only four peptides from a starting library of 108 strongly suggests that a generic XDGXXWX motif is not a determinant of cell binding, but rather the four sequences identified are highly specific binders rather than representative of a genus. Especially considering the far larger genus suggested by art indicating there are 500 naturally occurring amino acids, there is little evidence that the guidance from the specification allows one of ordinary skill in the art to both prepare all variants as well as assay them for specific binding to brain or spinal cord cells.
The Applicants’ arguments have been considered but are not persuasive. The rejection is maintained.
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.
Claim 2 is 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.
Regarding claim 2, the indefinite language is “an amino acid sequence which differs from the amino acid sequence of SEQ ID NO:1 by modification of one amino acid”. Claim 1 recites a sequence XDGXXWX, while SEQ ID NO:1 encodes a sequence NRGTEWD. This leads to a question of where any amino acid modification should occur, since SEQ ID NO: 1 does not match the base sequence motif of claim 1. Furthermore, the broadest reasonable interpretation of “modification” is not limited to just alteration of residue but could encompass chemical modification of the side chain. As such, it is not clear how the SEQ ID NO: 1 can also read upon claim 1 as submitted, rendering the metes and bounds unclear.
Response to Arguments:
The Applicants summarize the rejection of record.
The Examiner finds no material issues with the summary as provided.
The Applicants argue the general motif XDGXXWX differs from SEQ ID NO: 1 by replacement of one amino acid, i.e. a modification. The Applicants argue modification by one amino acid is supported by SEQ ID NOs: 2-5 above.
Even allowing that one amino acid might be changed, the claim still encompasses alternatives that do not further read upon SEQ ID NO: 1, i.e. those where any amino acid other than the second amino acid is modified. Furthermore, it does not appear that an amino acid differing from SEQ ID NO: 1 by one amino acid, i.e. a NDGTEWD sequence necessarily possess the ability to bind to cells of the brain and/or spinal cord as claimed.
The Applicants’ arguments have been considered but are not persuasive. The rejection is maintained.
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. 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 ZACHARY J MIKNIS whose telephone number is (571)272-7008. The examiner can normally be reached M-F 9-5.
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, Melissa Fisher can be reached at (571) 270-7430. 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.
/Z.J.M/Patent Examiner, Art Unit 1658 /SUDHAKAR KATAKAM/Primary Examiner, Art Unit 1658