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 .
Election/Restrictions
Applicant's election with traverse of Group I in the reply filed on 05/06/2026 is acknowledged. The traversal is on the ground(s) that there is no additional burden to search all claims. This is not found persuasive because search burden is not a requirement for restriction for cases filed under .
The requirement is still deemed proper and is therefore made FINAL.
Claims 29 and 36 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 05/06/2026.
Status of Claims
Claims 3-12, 14, 28, 31, and 33-34 were previously cancelled, in the amendment filed 09/11/2024. Claims 1-2, 13, 15-27, 29-30, 32, and 35-36 are pending. Claims 29 and 36 are withdrawn. Claims 1-2, 13, 15-27, 30, 32, and 35 will be examined on the merits.
Priority
Provisional application 63/216,189 is acknowledged as disclosing the claimed invention and the effective filing date is 06/29/2021.
Information Disclosure Statement
The Information Disclosure Statement filed on 05/06/2026 has been considered. Signed copies are enclosed.
The information disclosure statement filed 09/11/2024 fails to comply with 37 CFR 1.98(a)(2), which requires a legible copy of each cited foreign patent document; each non-patent literature publication or that portion which caused it to be listed; and all other information or that portion which caused it to be listed. It has been placed in the application file, but the information referred to therein has not been considered. Translated copies of foreign patents 6 and 10 were not provided and therefore these references were not considered.
Specification
The disclosure is objected to because of the following informalities:
The specification contains Table A and multiple "Table 1"s on pages 22, 71, and 89. The tables on pages 84 and 93 have no identifying letter or number. Examiner requests the tables throughout the specification are renumbered in a logical manner.
Additionally, SEQ ID NO:33 and 34 do not have a name or description in the table on page 102. Examiner requests that the table is amended with the description of SEQ ID NO: 33 and 34.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 2 is rejected 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. Claim 2 recites a list of possible functions or effects of the antibody of claim 1. These are all inherent properties of an antibody with the CDRs recited in claim 1, as these CDRs are primarily responsible for the structure and function of the antibody. Therefore, claim 2 does not further limit claim 1. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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 24 and 32 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.
Regarding claim 32, the phrase "for example" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Regarding claim 24, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
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.
Claim 13 is 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.
Claim 13 is drawn to the antibody of claim 1, with a VH comprising at least 80% identity to SEQ ID NO:4, and VL comprising at least 80% identity to SEQ ID NO: 12. The specification discloses a single antibody, HFB10-1E1hG1, that agonistically binds to OX-40. The ‘definitions’ section of the specification, beginning on page 36, provides the art-accepted definitions for antibodies and recites that CDRs are majorly responsible for binding (see lines 14-19 on page 37).
The antibody referred to as HFB10-1E1hG1, with a VH of SEQ ID NO: 4, and a VL of SEQ ID NO: 12, meets the written description provision of 35 U.S.C. 112(a). However, claim 13 encompasses far more than just this antibody. As claim 13 allows for up to 20% variation in the sequence of the VH and VL of HFB10-1E1hG1, and neither the instant claims nor the specification provide any guidance on which amino acid residues cannot be mutated in order to maintain the function of binding to OX-40, claim 13 is drawn to a broad genus of antibodies with 80% sequence identity to SEQ ID NO: 4 and SEQ ID NO:12.
Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, makes clear that "applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the 'written description' inquiry, whatever is now claimed." (See page 1117.) The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed." (See Vas-Cath at page 1116.)
To fulfill the written description requirements set forth under 35 U.S.C. 112(a), the specification must describe at least a substantial number of the members of the claimed genus, or alternatively describe a representative member of the claimed genus, which shares a particularly defining feature common to at least a substantial number of the members of the claimed genus, which would enable the skilled artisan to immediately recognize and distinguish its members from others, so as to reasonably convey to the skilled artisan that Applicant has possession of the claimed invention. To adequately describe the genus of antibodies, Applicant must adequately describe which combination of variable regions and framework regions that give rise to an antibody with the claimed immunological function. The instant specification, however, does not disclose distinguishing and identifying features of a representative number of members of the genus of antibodies to which the claims are drawn, such as a correlation between the structure of the antibody and its recited function (specifically binding OX-40), so that the skilled artisan could immediately envision, or recognize, at least a substantial number of members of the claimed genus of antibodies. The specification fails to disclose which amino acids might be added, replaced or deleted within the 80% sequence identity requirement so that the resultant antibody retains the binding specificity of its parent, or by which other amino acids the essential amino acids might be replaced so that the resultant antibody retains the binding specificity of its parent. Therefore, the specification fails to adequately describe at least a substantial number of members of the genus of antibodies to which the claims refer; and accordingly, the specification fails to adequately describe at least a substantial number of members of the claimed genus of antibodies.
As evidenced by the teachings of Skolnick et al., the art is unpredictable. Skolnick et al. (Trends in Biotechnology (2000) 18:34-39) discloses the skilled artisan is well aware that assigning functional activities for any particular protein or protein family based upon sequence homology is inaccurate, in part because of the multifunctional nature of proteins (see, e.g., the abstract; and page 34, Sequence-based approaches to function prediction). Even in situations where there is some confidence of a similar overall structure between two proteins, only experimental research can confirm the artisan's best guess as to the function of the structurally related protein (see, in particular, the abstract and Box 2). Thus, one skilled in the art would not accept the assertion, which is based only upon an observed similarity in amino acid sequence that a variant of a given polypeptide would necessarily bind to a given antibody.
As stated above, the CDRs are vital for antigen binding, as evidenced by Kapingidza et al. (Vertebrate and invertebrate respiratory proteins, lipoproteins and other body fluid proteins, 2020, 465-497) (see page 468, lines 1-4, and pages 476-482). Sela-Culang et al. (Frontiers in immunology, 2016, 4:302.) expands on the importance of antibody sequence and function, explaining that amino acid residues outside of the CDRs can influence antigen binding (abstract, whole document). Additionally, Clark et al. (Journal of Structural Biology, 2014, 185(2), 223-227) show that mutational effects on interfaces are often unpredictable (see pg. 223, 2nd col. 1st full para), and that it is easy to damage an interface and decrease binding affinity. Therefore, a person of ordinary skill in the art at the time of filling would understand residues within the CDRs are integral to antigen binding or maintaining the structure of the region that binds to the antigen and substitutions in these regions would affect one or both these attributes. As there is no art-recognized correlation between structure and function, it would be impossible for one of ordinary skill in the art to predict which variable CDRs, combinations of CDRs, or combinations of particular substitutions, would result in a structure that specifically binds OX-40.
Overall, based on the disclosure, the state of the art at the time of filing, a skilled artesian would have recognized that the applicant was not in possession of the claimed invention at the time of filing. Consequently, in accordance with the MPEP, only the antibody comprising the amino acid sequences of SEQ ID NOs 4 and 12, but not the full breadth of claim 13 regarding any amino acid sequence having at least 80% sequence identity to these SEQ ID NOs, meets the written description provision of 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph.
Applicant is reminded that Vas- Cath makes clear that the written description provision of 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, is severable from its enablement provision. (See page 1115).
Claim Rejections - 35 USC § 102
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.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1-2, 13, 15-21, 24-27, 30, 32 and 35 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by WO2021129874, Zhang et al., filed 12/28/2020, hereinafter Zhang.
Zhang et al. disclose an antibody with HCDR1 of SEQ ID NO: 1, an HCDR2 of Seq ID NO: 2, and HCDR3 of SEQ ID NO:3 in Zhang SEQ ID NO: 4 and an LCDR1 of SEQ ID NO: 9, an LCDR2 of SEQ ID NO: 10, and an LCDR3 of SEQ ID NO:11 in Zhang SEQ ID NO: 12 (see Zhang claim 1, paragraph [0011]), anticipating claim 1. Zhang discloses this antibody with a VH 96.5% identical to SEQ ID NO: 4 in Zhang SEQ ID NO: 4, and a VL with 100% sequence identity to SEQ ID NO: 12 in Zhang SEQ ID NO: 12 (see paragraph [0037]), anticipating claim 13. Zhang discloses a CH with 99.7% identity to SEQ ID NO: 5 in Zhang SEQ ID NO: 5, and a CL with 100% sequence identity to SEQ ID NO: 13 in Zhang SEQ ID NO: 12 (see paragraph [0040]), anticipating claim 15. Zhang teaches the antibody further comprising a heavy chain signal sequence with 100% sequence identity to SEQ ID NO: 6 in Zhang SEQ ID NO: 8, in paragraph [0041], anticipating claims 16 and 17. Zhang discloses the antibody as an IgG, anticipating claim 18, in paragraph [0042], and that the antigen binding fragment as Fab, Fab', F(ab')2, Fv, scFv, or sdAb in paragraph [0044], anticipating claim 19. Zhang teaches the antibody combined with a therapeutic agent, forming an antibody-drug conjugate, in paragraph [0045], anticipating claim 20. Zhang discloses a polynucleotide encoding a VH with 82% sequence identity to SEQ ID NO: 20 in Zhang SEQ ID NO: 50, a VL with 78.1% sequence identity to SEQ ID NO: 28 in Zhang SEQ ID NO: 51, a CH with 82% sequence identity to SEQ ID NO: 21 in Zhang SEQ ID NO: 50, and a CL with 79% sequence identity to SEQ ID NO: 29 in Zhang SEQ ID NO: 52 (see paragraphs [0048] and [0051]), anticipating claims 21-23. Zhang also teaches a vector and a host cell containing this polynucleotide in paragraphs [0052] and [0053], anticipating claims 24 and 25. Zhang disclose a method of producing a monoclonal antibody comprising culturing this cell in paragraph [0054], anticipating claim 26. Zhang teaches a pharmaceutical composition comprising this antibody and a pharmaceutically acceptable carrier in paragraphs [0056] and [0142], and a method of treating cancer comprising administering the antibody, ADC, or pharmaceutical composition of Zhang, wherein the cancer is selected from a group identical to the list in instant claim 32 in paragraphs [0056-0057], anticipating claims 30 and 32. Finally, Zhang teaches a kit comprising the antibody in paragraph [0062], anticipating claim 35. Therefore, Zhang et al. anticipates the instant claims.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1-2, 13, 15-27, 30, 32 and 35 is/are rejected under 35 U.S.C. 103 as being unpatentable over WO2021129874, Zhang et al., filed 12/28/2020, hereinafter Zhang, in view of Clancy et al., Nature Education 1.1 (2008): 101.
Zhang discloses an antibody with the disclosed sequences as recited above, under paragraph 18, thereby teaching claims 1, 2, 13, 15-17, and 21. Zhang also discloses all other identifying features of the instant claims, as recited above under paragraph 18, teaching claims 18-20, 24-27, 30, 32, and 35. However, Zhang does not explicitly teach a polynucleotide with SEQ ID NO: 20, 21, 28, or 29, as in instant claims 22 and 23.
Zhang discloses a polynucleotide encoding a VH with 77.2% sequence identity to SEQ ID NO: 20 in Zhang SEQ ID NO: 49, a VL with 78.1% sequence identity to SEQ ID NO: 28 in Zhang SEQ ID NO: 51, a CH with 82% sequence identity to SEQ ID NO: 21 in Zhang SEQ ID NO: 50, and a CL with 79% sequence identity to SEQ ID NO: 29 in Zhang SEQ ID NO: 52 (see paragraphs [0048] and [0051]). While these nucleotides sequences are not identical to the SEQ ID NOs disclosed in instant claims 22 and 23, they do encode the same peptide as the polynucleotides of SEQ ID NOs 20, 21, 28, and 29. One of ordinary skill in the art understands that there are multiple codons that can encode an amino acid (as seen in Clancy et al.), and that multiple polynucleotides can encode the same protein. Moreover, one of ordinary skill in the art would find it routine and conventional to create any polynucleotide that encodes a protein. There is no reason recited in the instant specification or the claims that this particular polynucleotide is better than any other polypeptide that encodes the instant antibody. Therefore, it would be obvious to one of ordinary skill in the art to translate the protein of Zhang into the polynucleotide of the instant claims. One would have reasonable expectation of success because doing so is well understood, routine, and conventional, as evidenced by Clancy et al. Therefore, instant claims 22 and 23 are obvious over Zhang in view of Clancy et al.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-2, 13, 15-27, 30, 32 and 35 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 4-8, 14, 17, 18, and 23-25 of copending Application No. 17/789,350 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because '350 discloses an antibody with the CDRs recited in claim 1, with 100% sequence identity between SEQ ID NOs: 4, 5, 6, 12, 13, 14, in both applications. ‘350 also discloses that the antibody is monoclonal in claim 6, can be an ADC in claim 8, in a pharmaceutical composition in claim 14, in a kit in claim 24, and a method of treating cancer comprising administering this antibody in claims 17 and 18. Therefore, the claims of ‘350 disclose the same subject matter as the instant claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Amelia Stephens whose telephone number is (571)272-1006. The examiner can normally be reached M-F 8-5 EST.
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/AMELIA STEPHENS/Examiner, Art Unit 1645
/ANNE M. GUSSOW/Supervisory Patent Examiner, Art Unit 1683
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