DETAILED ACTION
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. Applicant's amendment and remarks filed on 01/21/2026 are acknowledged.
Claims 1, 4-11, 13-14 and 16-20 are pending.
3. 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.
4. Claims 1, 4-11, 13-14 and 16-20 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
(i) Claim 1 is indefinite in the recitation of a “first” amino acid sequence, because the “second,” etc. amino acid sequence(s) is/are not defined.
(ii) Claim 5 is indefinite, because the recitation of “said Q63 substitution” lacks proper antecedent basis in the base claim.
(i) Claims 4-11, 13-14 and 16-20 are indefinite, because they encompass the indefinite limitations of the claim(s) on which they depend.
In view of the above, a person of ordinary skill in the art cannot unequivocally interpret the metes and bounds of the claims so as to understand how to avoid infringement. Applicant is reminded that any amendment must point to a basis in the specification so as not to add New Matter. See MPEP 714.02 and 2163.06.
5. The following is a quotation 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.
6. Claims 1, 4-6, 8, 10-11, 13-14, 16-18 and 20 are rejected under 35 U.S.C. 112(a) because the specification, while being enabling for a PD-L1 polypeptide comprising SEQ ID NO: 4 or SEQ ID NO: 5 carrying amino acid substitutions at the positions specified in claim 1, wherein the PD-L1 polypeptide binds to PD-1 with a Kd of at most 50 nM, does not reasonably provide enablement for a PD-L1 polypeptide “at least 70% identical” to SEQ ID NO: 4 or SEQ ID NO: 5 carrying amino acid substitutions at the positions specified in claim 1, wherein the PD-L1 polypeptide binds to PD-1 with a Kd of at most 50 nM. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims without undue experimentation.
Factors to be considered in determining whether undue experimentation is required to practice the claimed invention are summarized in In re Wands (858 F2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988)). The factors most relevant to this rejection are the scope of the claim, the amount of direction or guidance provided, limited working examples, the unpredictability in the art and the amount of experimentation required to enable one of skill in the art to make and use the claimed invention.
To make and use polypeptides within the scope of the claims, a person skilled in the art would need to produce such polypeptides and test them for binding affinity to PD-1.
Each of SEQ ID NO: 4 and SEQ ID NO: 5 is 116 amino acids in length, therefore, a polypeptide with 70% identity may contain up to 34 amino acid substitutions. Substituting 1 amino acid with each of the other amino acid in a 100 amino acid-long polypeptide results in 19x100=1,900 variants; substituting 2 amino acids yields 1900x(19x99)=3,573,900 variants, etc. The number of variants produced by substituting 28 amino acids in a 100 amino acid-long polypeptide produces over 10^83 variants, which exceeds the number of atoms in the observable universe, estimated to be between 1078 and 1082.
The number of compounds that can be screened by present-day ultrahigh throughput methods does not exceed 108 – 109, or hundreds of millions to one billion variants (e.g. Gantz et al. 2024; Jiang et al. 2023; Liu et al. 2023).
With this in mind, a skilled artisan would inescapably conclude that the number of variant polypeptides which those skilled in the art would need produce and test for the requisite functional properties is vastly beyond the reach of technology available at present, and for years to come. Accordingly, the required experimentation would be unnecessarily, and improperly, extensive and undue.
7. Claim 11 stands rejected under 35 U.S.C. 112(a) as failing to comply with the enablement requirement. The claim contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
It is maintained that the specification does not provide a sufficient enabling description of a method of treating a generically recited immune disorder, or a method of immuno-oncological treatment, comprising administering the recited PD-L1 polypeptide or a polynucleotide encoding the polypeptide.
The grounds of rejection pertaining to generically recited immune disorder and to immuno-oncological treatment, presented in section 8 of the previous Office action, are maintained for the reasons of record, as they apply to the amended claims.
Applicant’s arguments regarding sepsis and inflammation are accepted as sufficiently persuasive.
Applicant’s arguments regarding immuno-oncological treatment are unpersuasive, because they contradict Applicant’s arguments regarding sepsis and inflammation: if the protein of the invention suppresses immune response it will almost certainly exacerbate tumor growth.
Applicant has not meaningfully addressed the ground of rejection pertaining to a generically recited immune disorder.
Therefore, the grounds of rejection presented in section 8 of the previous Office action are maintained in part, as specified above, and are incorporated by reference herein as if reiterated in full.
8. The following US Patents share a coinventor and/or an assignee with the present application, and claim subject matter similar to that of the present claims, but do not contain patented claims which would anticipate or make obvious the presently claimed invention:
US Patents No. 10632174 and 11679142 recite B7-H1 (PD-L1) variants comprising amino acid substitutions Y56S, A69F, and C113Y relative to the mouse sequence, and substitutions Y56S, H69F, and R113Y relative to the human sequence. These patent neither teach nor recite substitutions at position P76 of the mouse sequence, or position V76 in the human sequence, and the available prior at does not teach or suggest this particular substitution.
9. Conclusion: no claim is allowed.
10. 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.
11. Any inquiry concerning this communication or earlier communications from the examiner should be directed to ILIA I OUSPENSKI whose telephone number is (571)272-2920. The examiner can normally be reached 9 AM - 5:30 PM.
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/ILIA I OUSPENSKI/ Primary Examiner, Art Unit 1644