RESPONSE TO APPLICANT’S AMENDMENT
1. Applicant's amendment, filed 03/19/2026, is acknowledged.
2. Claims 1, 19, 20, 38, 45-46, 51-52, 58 and 60 are pending.
3. Claims 1 and 19-20 stand withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected group.
4. Claims 38, 45-46, 51-52, 58 and 60 are under examination as they read on a bispecific hybrid antibody and compositions thereof comprising a first arm and a second arm bound to each other, in which the bispecific hybrid antibody is a human antibody, the first arm comprises an amino acid sequence of heavy chain variable region (VH) and an amino acid sequence of light chain variable region (VL) of an anti-PD-1 antibody, and the second arm comprises an amino acid sequence of heavy chain variable region (VH) and an amino acid sequence of light chain variable region (VL) of an anti-CD19 antibody.
5. Applicant’s IDS, filed 09/29/2025, 10/15/2025, 10/15/2025, 11/20/2025, 01/02/2026 and 02/27/2026 is acknowledged.
6. In view of the amendment filed on 03/19/2026, only the following rejections are remained.
7. 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.
9. Claims 38, 45-46, 51-52, 58 and 60 stand rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 of US Patent No. 12325746. Although the claims at issue are not identical, they are not patentably distinct from each other because claims Patent 12325746 are directed to bispecific antibody, having a first arm specifically binding to PD-1 and a second arm specifically binding to CD19, wherein (A) the first arm specifically binding to PD-1 has a heavy chain variable region (VH) comprising the amino acid sequence set forth in SEQ ID NO: 5, and a light chain variable region (VL) comprising the amino acid sequence set forth in SEQ ID NO: 25, and (B) the second arm specifically binding to CD19 has a VH comprising the amino acid sequence set forth in SEQ ID NO: 62, and a VL comprising the amino acid sequence set forth in SEQ ID NO: 25.
Applicant’s arguments, filed 03/19/2026, have been fully considered, but have not been found convincing.
Applicant request that this rejection be held in abeyance pending the resolution of the outstanding rejections under 35 USC § 112(a) and §103.
The rejection is maintained until a terminal disclaimer is filed.
10. The following is a quotation of 35 U.S.C. 112(a) (Pre-AIA 35 U.S.C. 112, first paragraph):
(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.
11. Claims 38, 45-46, 51-52, 58 and 60 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention for the same reasons set forth in the previous Office Action mailed 09/23/2025.
Applicant’s arguments, filed 03/19/2026, have been fully considered, but have not been found convincing.
Applicant traverses the rejections because the specification provides both sufficient written description and enablement for the claimed B cell-targeting PD-1 agonist. The specification and figures 1-15 of the present application discloses representative bispecific antibodies, along with detailed structural and functional data demonstrating their PD-1 agonist activity and B cell specificity. It further describes methods for generating and evaluating such antibodies-techniques that were well established in the art and do not require undue experimentation.
This is not found persuasive because the claims encompass a genus of B cell-targeting PD-1 agonists having a genus of first arm binding to PD-1 and a genus of second arm binding to CD19 in a particular structural format/orientation. As well as a genus of humanized or fully human-type anti-human PD-1 antibodies and humanized or fully human anti-CD19 antibodies formatted in a particular structural order that capable of binding to PD-1 and CD19 expressed B cells, and suppress B cell activation and/or memory T cell activation, a prophylactic, symptom progress-suppressive, recurrence-suppressive and/or therapeutic agent for autoreactive B cell mediated disease such as SLE, Graves Disease, myasthenia gravis, autoimmune hemolytic anemia, autoimmune thrombocytopenia, asthma, cryoglobulinemia, primary bile duct sclerosis or pernicious anemia, comprising the claimed B cell-targeting PD-1 agonist.
There are no known agonist anti-PD-1 antibodies and anti-CD19 antbodies used in treating autoimmunity. There does not appear to be an adequate written description in the specification as-filed of the essential structural feature that provides the recited function of suppressing B cell activation and/or memory T cell activation and capable of prophylactic, symptom progress-suppressive, recurrence-suppressive and/or therapeutic agent for autoreactive B cell mediated disease.
The claims are not supported by a description that satisfies 35 U.S.C. § 112, first paragraph. "[T]he test for sufficiency [of the written description] is whether the disclosure of the application relied upon reasonably conveys to those skilled in the art that the inventor had possession of the claimed subject matter as of the filing date." Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1351 (Fed. Cir. 2010) (en banc).
A "sufficient description of a genus ... requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can 'visualize or recognize' the members of the genus." Id.
at 1350. "[ A ]n adequate written description requires a precise definition, such as by structure, formula, chemical name, physical properties, or other properties, of species falling within the genus sufficient to distinguish the genus from other materials." Id.
"[F]unctional claim language can meet the written description requirement when the art has established a correlation between structure and function." Id. "But merely drawing a fence around the outer limits of a purported genus is not an adequate substitute for describing a variety of materials constituting the genus and showing that one has invented a genus and not just a species." Id.
The written description standard set out in Ariad applies to antibodies. See Amgen, Inc. v. Sanofi, 872 F.3d 1367, 1376-79 (Fed. Cir. 2017) ( applying the Ariad standard to antibodies claimed based on their binding and blocking activities); Abb Vie Deutschland GmbH & Co. v. Janssen
Biotech, Inc., 759 F.3d 1285, 1298-1300 (Fed. Cir. 2014) (same).
Because the Specification fails to describe any single antibody having any of the functions recited in the claims, it necessarily fails to describe a representative number of species within the claimed genera. In addition, the Specification fails to describe structural features common to members of the genus that would allow a skilled artisan to distinguish antibodies encompassed by the claim language from other antibodies. Finally, the Specification fails to disclose any correlation between the structure and function of the antibodies encompassed by the claim language. Therefore, the Specification fails to describe the antibodies required to practice the claimed method in a manner that reasonably conveys to those skilled in the art that Applicant was in possession of the claimed method as of the filing date of the instant application.
Regarding the enablement issue, there is insufficient guidance and direction as to make and use bispecific antibodies comprising humanized or full human-type anti-human PD-1/CD19 antibodies.
Amgen Inc. v. Sanofi, 143 S. Ct. 1243, 1254 (2023) states that:
If a patent claims an entire class of processes, machines, manufactures, or compositions of matter, the patent’s specification must enable a person skilled in the art to make and use the entire class. In other words, the specification must enable the full scope of the invention as defined by its claims. The more one claims, the more one must enable.
The broad genus of bispecific antibodies comprising humanized or full human-type anti-human PD-1/CD19 antibodies would require a person of ordinary skill in the art to engage in “undue experimentation” to make every species of B cell-targeting PD-1 agonist comprising bispecific antibodies comprising humanized or full human-type anti-human PD-1/CD19 antibodies covered by the claims. The Supreme Court’s decision leaves the law on enablement unchanged: a “genus” patent claim is not enabled unless every species covered by the claim is described in the patent, or the patent describes the genus by sufficient structural details that are shared by every species in the genus.
Applicant cannot disclose just three covered bispecific antibodies X, M and Fc-1 and then rely on the fact that a POSA would have known how to “raise” more B cell-targeting PD-1 agonist comprising humanized or fully human-type anti-human PD-1/CD19 antibodies, “could” humanize them, and that they all would work to suppress B cell activation and/or memory T cell activation capable of prophylactic, symptom progress-suppressive, recurrence-suppressive and/or therapeutic agent for autoreactive B cell mediated disease as required by the claims.
A POSA would have to make and screen a “vast” number of B cell-targeting PD-1 agonist comprising humanized or fully human-type anti-human PD-1/CD19 antibodies “by trial-and-error experimentation” to identify B cell-targeting PD-1 agonist comprising humanized or fully human-type anti-human PD-1/CD19 antibodies that satisfied the claimed invention.
12. Claims 38, 45-46, 51-52, 58 and 60 stand rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as containing 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 for the same reasons set forth in the previous Office Action mailed 09/23/2025.
Applicant’s arguments, filed 03/19/2026, have been fully considered, but have not been found convincing.
The novelty or unexpected nature of the claimed mechanism (namely, PD-1 agonism in B cells) does not undermine the adequacy of the written description or the enabling disclosure. The specification clearly demonstrates that the inventors conceived and successfully constructed antibodies exhibiting the claimed activity and provided experimental evidence of immune suppression consistent with PD-1 agonism. Accordingly, the subject matter is not presented as a mere hypothesis; rather, it is substantiated by specific examples and experimental results.
This is not found persuasive because the claims encompass a genus of B cell-targeting PD-1 agonists having a genus of first arm binding to PD-1 and a genus of second arm binding to CD19 in a particular structural format/orientation. As well as a genus of humanized or fully human-type anti-human PD-1 antibodies and humanized or fully human anti-CD19 antibodies formatted in a particular structural order that capable of binding to PD-1 and CD19 expressed B cells, and suppress B cell activation and/or memory T cell activation, a prophylactic, symptom progress-suppressive, recurrence-suppressive and/or therapeutic agent for autoreactive B cell mediated disease such as SLE, Graves Disease, myasthenia gravis, autoimmune hemolytic anemia, autoimmune thrombocytopenia, asthma, cryoglobulinemia, primary bile duct sclerosis or pernicious anemia, comprising the claimed B cell-targeting PD-1 agonist.
There are no known agonist anti-PD-1 antibodies and anti-CD19 antbodies used in treating autoimmunity. There does not appear to be an adequate written description in the specification as-filed of the essential structural feature that provides the recited function of suppressing B cell activation and/or memory T cell activation and capable of prophylactic, symptom progress-suppressive, recurrence-suppressive and/or therapeutic agent for autoreactive B cell mediated disease.
The claims are not supported by a description that satisfies 35 U.S.C. § 112, first paragraph. "[T]he test for sufficiency [of the written description] is whether the disclosure of the application relied upon reasonably conveys to those skilled in the art that the inventor had possession of the claimed subject matter as of the filing date." Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1351 (Fed. Cir. 2010) (en banc).
A "sufficient description of a genus ... requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can 'visualize or recognize' the members of the genus." Id.
at 1350. "[ A ]n adequate written description requires a precise definition, such as by structure, formula, chemical name, physical properties, or other properties, of species falling within the genus sufficient to distinguish the genus from other materials." Id.
"[F]unctional claim language can meet the written description requirement when the art has established a correlation between structure and function." Id. "But merely drawing a fence around the outer limits of a purported genus is not an adequate substitute for describing a variety of materials constituting the genus and showing that one has invented a genus and not just a species." Id.
The written description standard set out in Ariad applies to antibodies. See Amgen, Inc. v. Sanofi, 872 F.3d 1367, 1376-79 (Fed. Cir. 2017) ( applying the Ariad standard to antibodies claimed based on their binding and blocking activities); Abb Vie Deutschland GmbH & Co. v. Janssen
Biotech, Inc., 759 F.3d 1285, 1298-1300 (Fed. Cir. 2014) (same).
Because the Specification fails to describe any single antibody having any of the functions recited in the claims, it necessarily fails to describe a representative number of species within the claimed genera. In addition, the Specification fails to describe structural features common to members of the genus that would allow a skilled artisan to distinguish antibodies encompassed by the claim language from other antibodies. Finally, the Specification fails to disclose any correlation between the structure and function of the antibodies encompassed by the claim language. Therefore, the Specification fails to describe the antibodies required to practice the claimed method in a manner that reasonably conveys to those skilled in the art that Applicant was in possession of the claimed method as of the filing date of the instant application.
Regarding the enablement issue, there is insufficient guidance and direction as to make and use bispecific antibodies comprising humanized or full human-type anti-human PD-1/CD19 antibodies.
Amgen Inc. v. Sanofi, 143 S. Ct. 1243, 1254 (2023) states that:
If a patent claims an entire class of processes, machines, manufactures, or compositions of matter, the patent’s specification must enable a person skilled in the art to make and use the entire class. In other words, the specification must enable the full scope of the invention as defined by its claims. The more one claims, the more one must enable.
The broad genus of bispecific antibodies comprising humanized or full human-type anti-human PD-1/CD19 antibodies would require a person of ordinary skill in the art to engage in “undue experimentation” to make every species of B cell-targeting PD-1 agonist comprising bispecific antibodies comprising humanized or full human-type anti-human PD-1/CD19 antibodies covered by the claims. The Supreme Court’s decision leaves the law on enablement unchanged: a “genus” patent claim is not enabled unless every species covered by the claim is described in the patent, or the patent describes the genus by sufficient structural details that are shared by every species in the genus.
Applicant cannot disclose just three covered bispecific antibodies X, M and Fc-1 and then rely on the fact that a POSA would have known how to “raise” more B cell-targeting PD-1 agonist comprising humanized or fully human-type anti-human PD-1/CD19 antibodies, “could” humanize them, and that they all would work to suppress B cell activation and/or memory T cell activation capable of prophylactic, symptom progress-suppressive, recurrence-suppressive and/or therapeutic agent for autoreactive B cell mediated disease as required by the claims.
A POSA would have to make and screen a “vast” number of B cell-targeting PD-1 agonist comprising humanized or fully human-type anti-human PD-1/CD19 antibodies “by trial-and-error experimentation” to identify B cell-targeting PD-1 agonist comprising humanized or fully human-type anti-human PD-1/CD19 antibodies that satisfied the claimed invention.
13. 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.
14. Claims 38, 45-46 and 60 stand rejected under 35 U.S.C. 103 as being unpatentable over CN 106939050 A (IDS filed on 04/02/2020; Reference 12), as is evidenced by the specification at [0056], in view of Hornig e al (in Chames P., (Methods and Protocols, Second Edition, Methods in Molecular Biology, vol. 907; 2012) or Yang et al (Int. J. Mol. Sci., 18, 48, published on line Dec. 2016) for the same reasons set forth in the previous Office Action mailed 09/23/2025.
15. Claims 51-52 and 58 stand rejected under 35 U.S.C. 103 as being unpatentable over CN 106939050 A (IDS filed on 04/02/2020; Reference 12), as is evidenced by the specification at [0056], in view of Hornig e al (in Chames P., (Methods and Protocols, Second Edition, Methods in Molecular Biology, vol. 907; 2012) or Yang et al (Int. J. Mol. Sci., 18, 48, published on line Dec. 2016), as applied to claims 38, 45-46 and 60 above and further in view of US 20110177074 for the same reasons set forth in the previous Office Action mailed 09/23/2025.
Applicant’s arguments, filed 03/19/2026, have been fully considered, but have not been found convincing.
Applicant submits that this conclusion is based on an improper piecemeal selection of isolated data points that contradicts the overall teachings of the reference.
1. CN '050 teaches away from the claimed PD-1 agonist
While CN '050 mentions Clone 45 in passing, the actual bispecific antibody constructs disclosed and tested in the reference exclusively utilize the humanized anti-PD-1 antibody Clone 81 only. Clone 81 is derived from mouse anti-PD-1 antibodies Clones 3, 21, and 77, all of which are characterized by their ability to hinder (inhibit) the interaction between PD-1 and PD-L1. No information from the non-blocking Clone 45 was used for generating Clone 81 (see 3 paragraphs 0094, 0100, 0102 to 0104, and 0106 of CN '050). By specifically selecting blocking clones (3, 21, 77) to develop its lead bispecific candidate (Clone 81), CN '050 teaches a person of ordinary skill in the art (POSA) that blocking the PD-1/PD-L1 interaction is the preferred and necessary mechanism for its intended therapeutic goals.
This is not found persuasive because it appears that Applicant admits that CN `050 publication teaches both agonistic anti-PD-1 antibody such as clone 45 and antagonistic anti-PD-1 antibodies such as clones (3, 21, 77). A single species is sufficient to meet the claimed genus of agnostic anti-PD-1 antibody.
2. CN '050 is silent on the recited "PD-1 agonist suppresses B cell activation and/or
memory T cell activation"
The Office Action assumes that an antibody that "allows interaction" between PD-1 and PD-L1 is, by definition, an agonist. This is a technical error. A PD-1 agonist must actively stimulate the transmission of immune suppression signals into the cell. To the contrary, an antibody that "allows interaction" as disclosed in CN '050 may simply be a neutral binder that does not trigger any intracellular signaling. CN '050 is entirely silent regarding any agonistic signaling or B cell suppressive effects associated with Clone 45. In fact, the reference is directed toward activating T cells for cancer treatment the exact opposite of the immune suppression required for treating autoimmune diseases.
This is not found persuasive because Applicant is arguing a limitation not present in the claims, i.e., “actively stimulate the transmission of immune suppression signals into the cell”. Importantly, where the Patent Office has reason to believe that a functional limitation asserted to be critical for establishing novelty in the claimed subject matter may be an inherent characteristic of the prior art, it has the authority to require the applicant to prove that the subject matter shown in the prior art does not possess the characteristics relied on. In In re Schreiber, 128 F.3d 1473, 44 USPQ2d 1429 (Fed. Cir. 1997).
The Courts have held that there is no requirement that those of ordinary skill in the art know of the inherent property. See MPEP 2131.01(d) and MPEP 2112 - 2113.
Since the office does not have a laboratory to test the reference antibodies, it is applicant’s burden to show that the reference clone 45 is not PD-1 agonist antibody recited in the claim. See In re Best, 195 USPQ 430, 433 (CCPA 1977); In re Marosi, 218 USPQ 289, 292-293 (Fed. Cir. 1983); and In re Fitzgerald et al., 205 USPQ 594 (CCPA 1980).
16. No claim is allowed.
17. 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 extension fee 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.
18. Any inquiry concerning this communication or earlier communications from the examiner should be directed to MAHER M HADDAD whose telephone number is (571)272-0845. The examiner can normally be reached on Monday-Friday from7:00AM to 4:30PM. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Misook Yu, can be reached at telephone number 571-272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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April 7, 2026
/MAHER M HADDAD/ Primary Examiner, Art Unit 1644
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