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 .
Claims 21, 23, 46, 48, 50, 52-65, 67-75, 77-112, and 115-116 have been cancelled.
Election/Restrictions
Applicant’s election of Group II in the reply filed on 6/23/2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Upon further consideration of the claims, Group I, claims 1-20, 22, 24-28, and 113-114, will be rejoined with Group II as part of the elected invention..
Claims 44-45, 47, 49, 51, 66, and 76 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 6/23/2026.
Claims 1-20, 22, 24-43, and 113-114 are under consideration.
Claim 1 requires that at least one histidine residue in a light chain CDR is substituted with a different amino acid. CDR-L1 (SEQ ID NO: 4) has two histidines at amino acid positions 8 and 16. CDR-L2 (SEQ ID NO: 5) has no histidines. CDR-L3 (SEQ ID NO: 6) has one histidine at amino acid position 5. All claims dependent upon claim 1 must retain the recited CDRs (including any substitutions of histidine in SEQ ID NOS: 4 and 6) in order to be properly dependent. For example, the sequence variability permitted by the “at least 95% sequence identity” in SEQ ID NOS: 7 and 8 in claim 2 must be outside the CDRs.
SEQ ID NO: 7 has the CDRs of SEQ ID NOS: 1, 2, and 3 and SEQ ID NO: 8 has the CDRs of SEQ ID NOS: 4, 5, and 6. See claims 1 and 2.
In claim 4, SEQ ID NO: 8 has the CDRs of SEQ ID NOS: 9, 5, and 6. SEQ ID NO: 9 has the substitution of Ala for His at amino acid position 8. See also claim 3.
In claim 6, SEQ ID NO: 21 has the CDRs of SEQ ID NOS: 10, 5, and 6. SEQ ID NO: 10 has the substitution of Gln for His at amino acid position 8. See also claim 5.
In claim 8, SEQ ID NO: 22 has the CDRs of SEQ ID NOS: 11, 5, and 6. SEQ ID NO: 11 has the substitution of Tyr for His at amino acid position 8. See also claim 7.
In claim 10, SEQ ID NO: 23 has the CDRs of SEQ ID NOS: 12, 5, and 6. SEQ ID NO: 12 has the substitution of Ala for His at amino acid position 16. See also claim 9.
In claim 12, SEQ ID NO: 24 has the CDRs of SEQ ID NOS: 13, 5, and 6. SEQ ID NO: 13 has the substitution of Gln for His at amino acid position 16. See also claim 11.
In claim 14, SEQ ID NO: 25 has the CDRs of SEQ ID NOS: 14, 5, and 6. SEQ ID NO: 14 has the substitution of Tyr for His at amino acid position 16. See also claim 13.
In claim 16, SEQ ID NO: 26 has the CDRs of SEQ ID NOS: 15, 5, and 16. SEQ ID NO: 15 has the substitution of Ala for His at both amino acid position 8 and 16. SEQ ID NO: 16 has the substitution of Ala for His at amino acid position 5. See also claim 15.
In claim 18, SEQ ID NO: 28 has the CDRs of SEQ ID NOS: 17, 5, and 18. SEQ ID NO: 17 has the substitution of Gln for His at both amino acid position 8 and 16. SEQ ID NO: 18 has the substitution of Gln for His at amino acid position 5. See also claim 17.
In claim 20, SEQ ID NO: 29 has the CDRs of SEQ ID NOS: 19, 5, and 20. SEQ ID NO: 19 has the substitution of Tyr for His at both amino acid position 8 and 16. SEQ ID NO: 20 has the substitution of Tyr for His at amino acid position 5. See also claim 19.
Claims 5-8, 11-14, and 17-20 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims. The prior art does not disclose or suggest anti-CD228 antibodies having these sequences.
Claim Rejections - 35 USC § 103
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 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.
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.
Claims 1-4, 9-10, 15-16, 22, 24-35, and 113-114 are rejected under 35 U.S.C. 103 as being unpatentable over any of Sandall et al. (WO 2020/163225, of record, published 13 August 2020, filed 3 February 2020, inventors Sandall, Westendorf, and Lewis) or Sandall et al. (U.S. Patent Application Publication 2020/0246479, of record, published 6 August 2020, filed 3 February 2020, inventors Sandall, Westendorf, and Lewis) or Sandall et al. (U.S. Patent No. 11,617,798, of record, published 4 April 2023, filed 3 February 2020, inventors Sandall, Westendor, and Lewis) in view of Yamashita et al. (2019, of record).
WO 2020/163225, U.S. Patent Application Publication 2020/0246479, and U.S. Patent No. 11,617,798 are equivalent documents. WO 2020/163225 will be referenced.
Sandall et al. disclose an anti-CD228 antibody having SEQ ID NO: 7 (VH) and SEQ ID NO: 8 (VL). These sequences contain the CDRs recited in instant claim 1. SEQ ID NOS: 7-8 correspond to instant SEQ ID NO: 7-8. In particular, antibodies having variants of SEQ ID NO: 8 having at least 90% identity to SEQ ID NO: 8 are disclosed. See at least abstract and paragraph [0147]. Antigen-binding fragments such as Fab are disclosed. See at least claim 11 and instant claim 22. Full length antibodies are disclosed. See at least claim 12 and instant claim 24. Inclusion of light and heavy constant domains and IgG1 isotypes are disclosed. See at least claims 13-17 and instant claims 25-28. SEQ ID NOS: 17-19 of Sandall et al. correspond to instant SEQ ID NOS: 30, 32, and 31, respectively. Conjugates meeting the limitations of the instant claims are disclosed. See at least claims 18-25 and instant claims 29-35. Kits having antibodies or antibody conjugates are disclosed. See claims 88-19 and instant claims 113-114.
Yamashita et al. discloses alanine scanning mutagenesis on antibody sequences, including the CDRs, to further characterize the antibodies and potentially improve their pharmaceutical properties. See at least abstract, page 520, Figure 1, and Table S2.
In alanine scanning mutagenesis one or more amino acids is replaced by an alanine. Such analysis for SEQ ID NO: 8 would include substituting one or more histidines in LCDR1 and/or LCDR3 with another amino acid (in this case alanine) as recited in the instant claims. One would have been motivated to perform alanine scanning mutagenesis as taught by Yamashita et al. so in order to further characterize the anti-CD228 antibody of Sandall et al. and conjugates thereof.
Claims 36-43 are rejected under 35 U.S.C. 103 as being unpatentable over any of Sandall et al. (WO 2020/163225, of record, published 13 August 2020, filed 3 February 2020, inventors Sandall, Westendorf, and Lewis) or Sandall et al. (U.S. Patent Application Publication 2020/0246479, of record, published 6 August 2020, filed 3 February 2020, inventors Sandall, Westendor, and Lewis) or Sandall et al. (U.S. Patent No. 11,617,798, of record, published 4 April 2023, filed 3 February 2020, inventors Sandall, Westendor, and Lewis) in view of Yamashita et al. (2019, of record) and Bindman et al. (WO 2021/055865, published 25 March 2021, filed 18 September 2020).
Applicant is not entitled to benefit of the priority date 4 August 2020 for instant claims 36-43 as this subject matter is not found in provisional application 63/061,111. The effective filing date for these claims is 3 August 2021. Bindman et al. is valid prior art under 35 USC 102(a)(1) and 102(a)(2).
The Sandall and Yamashita et al. references are applied as above. They suggest embodiments of the instant antibodies where histidines in CDR-L1 and CDR-L3 are mutated to alanine and conjugates of these antibodies. These references do not disclose the conjugates of instant claims 36-43.
Bindman et al. discloses antibody drug conjugates (ADC) with the limitations in instant claims 36-43. See at least abstract and claims, particularly claims 1 and 7-14. The ligand unit can be any antibody. See at least paragraph [0002].
It would have been obvious to perform alanine scanning mutagenesis using SEQ ID NO: 8 by substituting one or more histidines in LCDR1 and/or LCDR3 with another amino acid (in this case alanine) as recited in the instant claims. It would have been further obvious to conjugate these antibodies as taught by Bindman et al. One would have been motivated to perform alanine scanning mutagenesis as taught by Yamashita et al. so in order to further characterize the anti-CD228 antibody of Sandall et al. as well as conjugates thereof as suggested by Bindman 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 1-4, 9-10, 15-16, 22, 24-35, and 113-114 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims and 1-25, 88-99, and 113-114 of U.S. Patent No. 11,617,798 (of record) in view of Yamashita et al. (2019, of record).
Issued claim 1 is directed to an anti-CD228 antibody having the CDRs of SEQ ID NOS: 1-6. No histidine substitutions are required for CDR-L1 and CDR-L3. Issued claims 6-9 recite
SEQ ID NO: 7 (VH) and SEQ ID NO: 8 (VL). These sequences contain the CDRs recited in instant claim 1. SEQ ID NOS: 7-8 correspond to instant SEQ ID NO: 7-8. In particular, antibodies having variants of SEQ ID NO: 8 having at least 95% identity to SEQ ID NO: 8 are claimed. Antigen-binding fragments such as Fab are disclosed. See issued claims 10-11 and instant claim 22. Full length antibodies are disclosed. See issued claim 12 and instant claim 24. Inclusion of light and heavy constant domains and IgG1 isotypes are disclosed. See issued claims 13-17 and instant claims 25-28. SEQ ID NOS: 17-19 in the issued claims correspond to instant SEQ ID NOS: 30, 32, and 31, respectively.. Conjugates meeting the limitations of the instant claims are disclosed. See issued claims 18-25 and instant claims 29-35. Kits having antibodies or antibody conjugates are disclosed. Pharmaceutical compositions are disclosed. See issued claims 88-89 and 113-114 and instant claims 113-114.
Yamashita et al. discloses alanine scanning mutagenesis on antibody sequences, including the CDRs, to further characterize the antibodies and potentially improve their pharmaceutical properties. See at least abstract, page 520, Figure 1, and Table S2.
In alanine scanning mutagenesis one or more amino acids is replaced by an alanine. Such analysis for SEQ ID NO: 8 would include substituting one or more histidines in LCDR1 and/or LCDR3 with another amino acid (in this case alanine) as recited in the instant claims. One would have been motivated to perform alanine scanning mutagenesis as taught by Yamashita et al. so in order to further characterize the anti-CD228 antibody of the issued claims and conjugates thereof.
The instant claims are not patentably distinct from the issued claims in view of Yamashita et al.
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 1-2, 22, 24-43, and 113-114 are 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 the antibodies of claims 3-20, does not reasonably provide enablement for all antibodies encompassed by the claims. 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.
Claim 1 requires that at least one histidine residue in a light chain CDR is substituted with a different amino acid. CDR-L1 (SEQ ID NO: 4) has two histidines at amino acid positions 8 and 16. CDR-L2 (SEQ ID NO: 5) has no histidines. CDR-L3 (SEQ ID NO: 6) has one histidine at amino acid position 5. All claims dependent upon claim 1 must retain the recited CDRs (including any substitutions of histidine in SEQ ID NOS: 4 and 6) in order to be properly dependent. For example, the sequence variability permitted by the “at least 95% sequence identity” in SEQ ID NOS: 7 and 8 in claim 2 must be outside the CDRs.
The specification enables the antibodies of claims 3-20 where the histidines in CDR-L1 at either amino acid position 8 or 16 is replaced with Ala, Gln, or Tyr and where the histidines in CDR-L1 and CDR-L3 are each replaced with Ala or each replaced with Gln, or each replaced with Tyr. The specification demonstrates that these antibodies retain antigen-binding activity. See at least specification Tables 2-4.
However, claims 1 and 2 embrace substituting any amino acid at the three histidine positions and in any combination. At least for example, the specification does not exemplify replacing only the histidine in CDR-L3 or replacing the three histidines (two in CDR-L1 and one in CDR-L3) where one histidine is replaced by Ala, one histidine is replaced by Gln, and one histidine is replaced by Tyr. The results from the examples cannot be extrapolated to predict antigen binding activity for these other embodiments. Histidine is a basic amino acid. Alanine is an aliphatic amino acid, glutamine is an acidic amino acid, and tyrosine is an aromatic amino acid. At least for example, no hydroxyl or sulfur containing amino acids such as cysteine were made to the CDRs and the antibody shown to retain activity. At least for example, no cyclic amino acids such as proline were made to the CDRs and the antibody shown to retain activity. The antigen binding activity of an antibody is dependent upon its six CDRs. Changing amino acids in the CDRs would have been known to affect and in some cases abolish antigen binding. See at least Herold (2017) which discusses effects of mutations on domain structure, stability, association and antigen binding in an antibody. See also Iwahashi et al. (of record) which also discusses effects of CDR substitutions. The exemplified antibodies are not representative antibodies commensurate in scope to the claims and cannot be used to predict the activity of antibodies having other combinations of mutations.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARIANNE P ALLEN whose telephone number is (571)272-0712. The examiner can normally be reached 7:00-3:30 EST Monday-Friday.
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/Marianne P Allen/Primary Examiner, Art Unit 1647
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