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
Election Response
The Election filed 12/19/2025 in response to the Office Action of 10/20/2025 is acknowledged. Applicant elected with traverse Group I, claims 1, 3, 4, 7, 10, 12-17, and 19-22, and the following species: (A) residues corresponding to 7, 8, 9, 21, 22, 24, 26, 29, 31, 33, 40, 42, 44, and 46 of the Sac7 sequence, (B) SEQ ID NO: 38, (3) sac7d is conjugated to another polypeptide. Examiner has rejoined all groups and species.
Claims 1, 3, 4, 7, 10, 12-17, and 19-25 are pending and are currently pending and under prosecution.
Nucleotide and/or Amino Acid Sequence Disclosures
Summary of Requirements for Patent Applications Filed On Or After July 1, 2022, That Have Sequence Disclosures
37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, 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 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted:
1. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 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”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying:
a. the name of the XML file
b. the date of creation; and
c. the size of the XML file in bytes; or
2. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 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 statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying:
a. the name of the XML file;
b. the date of creation; and
c. the size of the XML file in bytes.
SPECIFIC DEFICIENCIES AND THE REQUIRED RESPONSE TO THIS NOTICE ARE AS FOLLOWS: This application contains sequence disclosures in accordance with the definitions for nucleotide and/or amino acid sequences set forth in 37 CFR 1.831(a) and 1.831(b). However, this application fails to comply with the requirements of 37 CFR 1.831-1.834. The examiner has noted that Figure 1 does not identify the SEQ ID Nos for the recited sequences, or is not listed in the specification under description of the figures in the specification.
Applicant must provide:
• A replacement “Sequence Listing XML” part of the disclosure, as described above in item 1. or 2., as well as
• A statement that identifies the location of all additions, deletions, or replacements of sequence information in the “Sequence Listing XML” as required by 1.835(b)(3);
• A statement that indicates support for the amendment in the application, as filed, as required by 37 CFR 1.835(b)(4);
• A statement that the “Sequence Listing XML” includes no new matter in accordance with 1.835(b)(5); and
• A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required incorporation by reference paragraph as required by 37 CFR 1.835(b)(2), consisting of:
o A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
o A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
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, 3, 4, 7, 10, 12-17, and 19-25 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 enablement requirement. The claim(s) 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.
The claims are drawn to a polypeptide comprising a variant of a member of a Sac7d that binds to human PD-L1 and inhibits binding of PD-L1 with PD1, wherein the variant comprises from 4 to 20 mutated residues located within an interface of binding of the member of the Sac7d family to its natural ligand, the mutated residues being selected from positions V2, K3, K5, K7, Y8, K9, G10, E14, T17, K21, K22, W24, V26, G27, K28, M29, S31, T33, D36, N37, G38, K39, T40, A44, S46, E47, K48, D49, A50 and P51 of Sac7d, wherein the variant comprises either:
Y8M, V26L, S31L, R42L, A44F substitutions or
Y8I, V26L, S31L, R42M, and A44L substitutions,
with numbering corresponding to SEQ ID NO: 1.
Thus, the claim is directed to any change of the residues as recited above, in any of the 30 positions listed above. It is unclear what the mutations will be, and unclear what residues can the residues be mutated to without disrupting the function. Thus, the claim is drawn to an unclear and partial structure, and lacks support for enablement.
The instant specification recites mutations known in the art and demonstrated in WO 2012/150314 and WO2008 068837. The instant specification discloses that the Sac7d protein family is described in WO 2008/068637. The instant specification discloses that WO 2012/150314 shows that mutations from one protein of the Sac7d family can be carried to another protein of the same family, and one can introduce the mutated amino acids of the Sac7d mutant within the scaffold of another protein, using the sequence alignment of figure 1. The instant specification discloses that in of the published specification that it is preferred when 7, 8,9, 10, 11, 12, 13 or 14 amino acids are mutated in the binding site of the OB-fold domain. [pgs 28-29 of the specification] The instant specification does not disclose what these specific mutations may be and still retain function. The instant specification does not demonstrate the mutations in all of the sites as recited the claim and whether it would function as claimed.
It is well understood in the art that mutations in amino acids can have structural and functional consequences, as taught by Sotomayor-Vivas et al (Linking protein structural and functional change to mutation using amino acid networks. PLoS One. 2022 Jan 21;17(1)). It is impossible to determine which residue(s) can be mutated for another residue, to still have the same effect and function. With regards to mutations in Sac7d, the Chen et al (Probing the DNA kink structure induced by the hyperthermophilic chromosomal protein Sac7d. Nucleic Acids Res. 2005 Jan 14;33(1):430-8) teaches that some mutations/amino acid substitutions have an effect on function of the protein. [pgs 436-437 Discussion]
Applicant is reminded that MPEP 2164.03 teaches “the amount of guidance or direction needed to enable the invention is inversely related to the amount of knowledge in the state of the art as well as the predictability of the art. In re Fisher, 428 F.2d 833, 166 USPQ 18, 24 (CCPA 1970) the amount of guidance or direction refers to that information in the application, as originally filed, that teaches exactly how to make or use the invention. The more that is known in the prior art about the nature of the invention, how to make, and how to use the invention, and the more predictable the art is, the less information needs to be explicitly state in the specification. In contrast, if little is known in the prior art about the nature of the invention and the art is unpredictable, the specification would need more detail as how to make and use the invention in order for it to be enabling. Given lack of guidance in the specification, no one skilled in the art would accept the assertion that the claimed invention would function as contemplated or as claimed based only on the information in the specification and that known in the art at the time the invention was made.
The specification provides insufficient guidance with regard to these issues and provides no working examples which would provide guidance to one skilled in the art and no evidence has been provided which would allow one of skill in the art to predict that the invention will function as contemplated or claimed with a reasonable expectation of success. For the above reasons, it appears that undue experimentation would be required to practice the claimed invention
Claims 2 rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for treating cancer comprising administering the polypeptide of claim 1 as monotherapy, does not reasonably provide enablement for the combination of the polypeptide of claim 1 with a chemotherapy agent or a CAR T-cell The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to practice the invention commensurate in scope with these claims.
BREADTH OF THE CLAIMS: Claims 24 and 25 recite that the peptide is administered in combination with chemotherapy or treatment with CAR T-cells.
PRESENCE OR ABSENCE OF EXAMPLES: The instant specification discloses the following: Example 3 demonstrates the comparison of an anti-HSP110 variant alone or combination with anti-PD-L1 variant. Example 4-6 demonstrates the efficacy of the variant in in vivo cancer models. None of the examples in the specification demonstrate the instantly claimed polypeptide in combination with either chemotherapy or treatment with a CAR T-cell.
STATE OF THE ART: It is well known that the art of anti-cancer therapy is highly unpredictable, for example, Gura (Science, 1997, 278:1041-1042) teaches that researchers face the problem of sifting through potential anticancer agents to find ones promising enough to make human clinical trials worthwhile and teach that since formal screening began in 1955, many thousands of drugs have shown activity in either cell or animal models that only 29 have actually been shown to be useful for chemotherapy See p. 1041, see 1st and 2nd para. Furthermore, Kaiser (Science, 2006, 313: 1370) teaches that 90% of tumor drugs fail in patients. See 3rd col., 2nd to last para. Additionally, Chames et al (British J. of Pharmacology, 2009, 157, 220-233) teach that there are several challenges to development therapeutic antibodies. These challenges include functional limitations such as inadequate pharmacokinetics, tissue accessibility and impaired interactions with the immune system (Abstract). Additionally, Chames teaches several limitations of therapeutic antibodies such as affinity between the antibody and its antigen, competition with patient’s IgG, and efficiency issues in triggering the immune response (pages 224-225).
PREDICTABILITY: The specification lacks the critical steps necessary in presenting some type of predictable response in a population of hosts deemed necessary to treat cancer in combination with the instantly claimed combination with either chemotherapy and/or a CAR T-cell. Thus, considering the high level of skill in the art, the state of the art, the level of predictability, and the guidance and examples provided, the experimentation required to enable the full scope of the claimed invention would not be reasonable.
QUANTITY OF EXPERIMENTATION: Undue experimentation would be required to determine claimed agent is administered with what agent to treat and prevent each disorder claimed. MPEP 2164.01 recites that “The test of enablement is not whether any experimentation is necessary, but whether, if experimentation is necessary, it is undue. In re Angstadt, 537 F.2d 498, 504, 190 USPQ 214, 219 (CCPA 1976)”. The experimentation needed to practice this method is undue and unreasonable as it requires determining whether the claimed agents treats cancer as claimed. A person skilled in the art will not be able to use the invention without undue experimentation. (In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988))
Accordingly, the instant claims do not comply with the enablement requirement of §112, since to practice the invention claimed in the patent a person of ordinary skill in the art would have to engage in undue experimentation, with no assurance of success.
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 22-25 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.
Claims 22-25 recite the limitation “a polypeptide of claim 1”. The claims should read “the polypeptide of claim 1”. There is insufficient antecedent basis for this limitation in the claims.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SARAH A ALSOMAIRY whose telephone number is (571)272-0027. The examiner can normally be reached Monday-Friday 7:30 AM to 5:30 PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Gregory Emch can be reached at (571) 272-8149. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SARAH A ALSOMAIRY/Examiner, Art Unit 1646
/Zachariah Lucas/Supervisory Patent Examiner, Art Unit 1600
Prosecution Insights