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 1-45 and 48-51 are cancelled.
Claims 46-47 are currently amended.
Claims 46-47 and 52-73 are pending and under examination on the merits.
Priority
This application is a DIV of U.S. Application Serial No. 17/710,243, filed March 31, 2022 and claims priority to NL 2027892, filed on March 31, 2021.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 06/12/2026 has been entered.
Withdrawn Objections and Rejections
The rejections of the claims for lack of written description are withdrawn in light of the sufficiently narrowing claim amendments dated 06/12/2026. The rejections of the claims for lack of enablement are withdrawn in light of the sufficiently narrowing claim amendments dated 06/12/2026. The rejections for double patenting are withdrawn and replaced with the rejections for double patenting as presented in this Office Action to better account for the amended claim scope resulting from the 06/12/2026 claim amendments.
IDS
The information disclosure statement (IDS) filed 07/24/2026 has been considered.
Newly Necessitated-Claim Objections
Claim 54 is objected to under 37 CFR 1.75 as being a substantial duplicate of claim 53. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Claims 58-59 are objected to for their dependence from rejected based claim 46, but would be allowable if re-written in independent form.
Newly Necessitated-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 46-47, 52-56, and 60-73 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over the claims of copending Application No. 17/708,901 (reference application) in view of He et al (Immune checkpoint signaling and cancer immunotherapy. Cell Res. 2020 Aug;30(8):660-669. doi: 10.1038/s41422-020-0343-4).
This is a provisional nonstatutory double patenting rejection.
Regarding claims 46-47 and 52, the reference application recites an anti-PD-1 antibody having identical CDRs to the anti-PD-1 antibody of the instant Application. Reference SEQ ID NO: 7 comprises instant CDR SEQ ID NOs: 43-44-27. Reference SEQ ID NO: 6 comprises instant CDR SEQ ID NOs: 40-41-27 and 43-44-27. Reference SEQ ID NO: 5 comprises instant CDR SEQ ID NOs: 37-38-39. Reference SEQ ID NO: 4 comprises instant CDR SEQ ID NOs: 34-35-36. Reference SEQ ID NO: 3 comprises instant CDR SEQ ID NOs: 31-32-33. Reference SEQ ID NO: 2 comprises instant CDR SEQ ID NOs: 28-29-30. Reference SEQ ID NO: 1 comprises instant CDR SEQ ID NOs: 25-26-27 (see reference claims 17 and 52-65). Reference SEQ ID NO: 1 is 100% identical to the instant SEQ ID NO: 1. Reference SEQ ID NO: 2 is 100% identical to the instant SEQ ID NO: 2. Reference SEQ ID NO: 3 is 100% identical to the instant SEQ ID NO: 3. Reference SEQ ID NO: 4 is 100% identical to the instant SEQ ID NO: 4. Reference SEQ ID NO: 5 is 100% identical to the instant SEQ ID NO: 5. Reference SEQ ID NO: 6 is 100% identical to the instant SEQ ID NO: 6. Reference SEQ ID NO: 7 is 100% identical to the instant SEQ ID NO: 7 and is 93.3% identical to instant SEQ ID NO: 9 (see reference claims 17 and 52-65). The inclusion of the PD-1 binding moiety in a bivalent IgG format, absent evidence to the contrary, would not have been understood to alter measured binding affinity between the moiety and the PD-1 such that said modification would have been a functionally equivalent, obvious variant as presently claimed. Because the claims of the reference application disclose the same structure that is required by the instant claims, the co-pending (reference) claims are held to make obvious the instant claims because function inherently flows from structure so the binding and function would presumably be the same.
The copending reference application claims does not appear to explicitly provide motivation to use the claimed antibody to treat disease.
However, the specification can be used to determine the utility of a product. See Sun Pharmaceutical Industries v. Eli Lilly and Co., 611 F. 3d 1381, 1385 (CAFC 2010) (“Our prior obviousness-type double patenting decisions in Geneva and Pfizer … we found claims of a later patent invalid for obviousness-type double patenting where an earlier patent claimed a compound, disclosing its utility in the specification, and a later patent claimed a method of using the compound for a use described in the specification of the earlier patent”). See also MPEP § 804(II)(B)(2)(a).
The specification of the copending reference application teaches that an object of its disclosure is to provide new agents for treatment of human disease, in particular for the treatment of cancer (see for example page 2, lines 19-20; page 3, lines 14-19; and page 40, lines 21-24).
The reference application does not clearly teach that the cancers to be treated are blood, skin, lung, liver, bladder, and/or kidney cancers, specifically.
However, He et al teach that the most successful immune check point blockade therapy is anti-PD-1/PD-L1 therapy that has been approved to treat a wide variety of cancer types, such as blood, skin, lung, liver, bladder and kidney cancers (see for example, column 1 bridging column 2 of page 660).
Therefore, the artisan would have found it obvious to use the binding moiety comprising the instantly claimed sequences (alone, as a fragment, or as a bispecific/multispecific) to treat a human disease, such as cancer including blood, skin, lung, liver, bladder and kidney cancers.
Regarding claims 53-54, the reference application claims the above noted HCDR combination/HCVR further comprising LCDR1-3 having SEQ ID NOs: 60, 61, and 62, respectively, where reference SEQ ID NO: 60 is 100% identical to instant SEQ ID NO: 49, reference SEQ ID NO: 61 is 100% identical to instant SEQ ID NO: 50, and reference SEQ ID NO: 62 is 100% identical to instant SEQ ID NO: 51 (see for example, reference claim 51).
Regarding claims 55-56, the reference application claims the instantly recited HCDR combinations further comprising an LCVR having SEQ ID NO: 24, where reference SEQ ID NO: 24 is 100% identical to instant SEQ ID NO: 16 (see for example, reference claim 47).
Regarding claim 60-61, Reference SEQ ID NO: 1 comprises instant CDR SEQ ID NOs: 25-26-27 (see reference claims 17 and 52-65). Reference SEQ ID NO: 1 is 100% identical to the instant SEQ ID NO: 1. The reference application claims the above noted HCDR combination/HCVR further comprising LCDR1-3 having SEQ ID NOs: 60, 61, and 62, respectively, where reference SEQ ID NO: 60 is 100% identical to instant SEQ ID NO: 49, reference SEQ ID NO: 61 is 100% identical to instant SEQ ID NO: 50, and reference SEQ ID NO: 62 is 100% identical to instant SEQ ID NO: 51 (see for example, reference claim 51). The reference application further claims a PD-1 binding domain having an HCVR comprising SEQ ID NO: 1 and an LCVR comprising SEQ ID NO: 24 (where reference SEQ IS NOs: 1 and 24 are 100% identical to instant SEQ ID NOs: 1 and 16, respectively) (see for example, reference claim 52). Note that SEQ ID NO: 24 of the reference Application comprises sequences 100% identical to instant SEQ ID NOs: 49, 50, and 51.
Regarding claims 62-63, as discussed above, the reference application claims a PD-1 binding domain where the HCVR comprises one of SEQ ID NOs: 1-8 and an LCVR that comprises SEQ ID NO: 24, where reference SEQ ID NO: 2 comprises instant CDR SEQ ID NOs: 28-29-30 and reference SEQ ID NO: 24 is 100% identical to instant SEQ ID NO: 16 and comprises LCDR1-3 having amino acid sequences identical to instant SEQ ID NOs: 49, 50, and 51, respectively (see for example, reference claim 15).
Regarding claims 64-65, as discussed above, the reference application claims a PD-1 binding domain where the HCVR comprises one of SEQ ID NOs: 1-8 and an LCVR that comprises SEQ ID NO: 24, where reference SEQ ID NO: 3 comprises instant CDR SEQ ID NOs: 31-32-33 and reference SEQ ID NO: 24 is 100% identical to instant SEQ ID NO: 16 and comprises LCDR1-3 having amino acid sequences identical to instant SEQ ID NOs: 49, 50, and 51, respectively (see for example, reference claim 15).
Regarding claims 66-67, as discussed above, the reference application claims a PD-1 binding domain where the HCVR comprises one of SEQ ID NOs: 1-8 and an LCVR that comprises SEQ ID NO: 24, where reference SEQ ID NO: 4 comprises instant CDR SEQ ID NOs: 34-35-36 and reference SEQ ID NO: 24 is 100% identical to instant SEQ ID NO: 16 and comprises LCDR1-3 having amino acid sequences identical to instant SEQ ID NOs: 49, 50, and 51, respectively (see for example, reference claim 15).
Regarding claims 68-69, as discussed above, the reference application claims a PD-1 binding domain where the HCVR comprises one of SEQ ID NOs: 1-8 and an LCVR that comprises SEQ ID NO: 24, where reference SEQ ID NO: 5 comprises instant CDR SEQ ID NOs: 37-38-39 and reference SEQ ID NO: 24 is 100% identical to instant SEQ ID NO: 16 and comprises LCDR1-3 having amino acid sequences identical to instant SEQ ID NOs: 49, 50, and 51, respectively (see for example, reference claim 15).
Regarding claims 70-71, as discussed above, the reference application claims a PD-1 binding domain where the HCVR comprises one of SEQ ID NOs: 1-8 and an LCVR that comprises SEQ ID NO: 24, where reference SEQ ID NO: 6 comprises instant CDR SEQ ID NOs: 40-41-27 and reference SEQ ID NO: 24 is 100% identical to instant SEQ ID NO: 16 and comprises LCDR1-3 having amino acid sequences identical to instant SEQ ID NOs: 49, 50, and 51, respectively (see for example, reference claim 15).
Regarding claims 72-73, as discussed above, the reference application claims a PD-1 binding domain where the HCVR comprises one of SEQ ID NOs: 1-8 and an LCVR that comprises SEQ ID NO: 24, where reference SEQ ID NO: 6 comprises instant CDR SEQ ID NOs: 40-41-27 and 43-44-27 and reference SEQ ID NO: 24 is 100% identical to instant SEQ ID NO: 16 and comprises LCDR1-3 having amino acid sequences identical to instant SEQ ID NOs: 49, 50, and 51, respectively (see for example, reference claim 15).
Claim 57 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over the claims of copending Application No. 17/708,901 (reference application) and He et al, as applied to claims 46-47, 52-56, and 60-73, in further view of Janeway et al (The Immune System in Health and Disease. 5th edition. New York: Garland Science; 2001. The structure of a typical antibody molecule. Available from: https://www.ncbi.nlm.nih.gov/books/NBK27144/).
This is a provisional nonstatutory double patenting rejection.
Regarding claim 57, the reference application and He et al teach as set forth above.
The reference application in view of He et al does not explicitly recite that the PD-1 binding domain comprises a CH1 and CL region.
However, Janeway et al, teaching the structure of a typical antibody molecule, teach that the typical antibody (a binding domain) comprises a CH1 and a CL region (see for example, the title of the Janeway reference and Figure 3.1 (paying particular attention to part b)) at page 1/6).
It would have been prima facie obvious to the person of ordinary skill in the art to arrive at the claimed invention from the disclosures of the reference Application and Janeway et al. The artisan would have been motivated to make and use the invention as claimed because Janeway et al teach the typical generic structure of an antibody which the artisan would find to be an obvious format to use with the structures of the reference application to facilitate therapeutic PD-1 binding. The artisan would have had a reasonable expectation of success based on the cumulative disclosures of these prior art references.
Applicant’s Arguments and Responses
A. Applicant argues for withdrawal of the rejections for double patenting alleging that the reference application does not teach a therapeutic use of the antibody and that the Examiner has not provided motivation to remove the second binding moiety of the reference application’s claimed composition (see page 11 of the 06/12/2026 remarks).
Response: Sun Pharmaceuticals v. Eli Lilly Co would appear to apply such that the disclosure’s specification disclosing therapeutic use of the a bispecific may reasonably be used in the rejection for double patenting. The instant claims recite a method of using an antibody comprising anti-PD-1 binding capacity/structures and do not preclude the presence of a second binding moiety. Moreover, where the reference application teaches the instantly claimed anti-PD-1 and He et al teach the use of anti-PD-1 antibodies as PD-1 therapy for treating the enumerated cancers, the combination of the reference application and He et al make obvious the instant claims as presently drafted. The rejections for double patenting over the reference application and cited supporting references as presented in this Office Action are maintained at this time.
Suggestions to Applicant
To overcome the rejection of double patenting over reference application 17/708,901, the Examiner suggest filing of a terminal disclaimer.
Conclusion
No claim is allowed.
As noted in the office action dated 09/17/2025, the sequences having 100% identify (no substitutions) to the HCDR combinations recited in claim 46 have been searched and are deemed to be free from the prior art. SEQ ID NO: 9 as instantly claims, comprising respective HCDR1-3 SEQ ID NOs: 22-23-24 is free from the prior art and is not claimed by the reference application noted in the rejections for double patenting as set forth above. There being no reason for refusal, claims 58 and 59, explicitly requiring HCDR1-3 SEQ ID NOs: 22-23-24 and SEQ ID NO: 9, respectively, without any variation are deemed to be free from the prior art and in condition for allowance upon satisfactory resolution of the issues set forth above.
The prior art made of record and not relied upon continues to be considered pertinent to applicant's disclosure.
Ono Pharmaceutical Co., Ltd., hereinafter ‘Ono’, (WO2006121168A1; as cited on the 04/03/2024 IDS) teaches an anti-PD-1 antibody comprising an HCVR and LCVR comprising sequences which are 100% homologous to instant SEQ ID NOs: 20 and 21, respectively (see Ono at claim 8, SEQ ID NOs: 4 and 11, respectively; see also Ono at page 3). Ono teaches that this antibody binds human PD-1 with an affinity of 1X10^-7M K.sub.D or less, with a preferred embodiment binding human PD-1 with an affinity of 1X10^-7M K.sub.D or less (see pages 2-3 of Ono).
Crescendo Biologics Ltd., hereinafter CBL, (US 20190322749 A1; as cited on the 04/03/2024 IDS) CBL teaches an anti-PD-1 VH with a biasing affinity for human PD-1 of 7.82X10^-11 K.sub.D M (See row 1 of table 13). Note that this is a 10 fold greater affinity for human-PD-1 than is explicitly recited by the reference antibody as taught by Ono, as discussed and cited, above. CBL further teaches that, “[b]inding kinetics of certain humabodies [VH, trademark of Crescendo Biologics Ltd] binding to human PD-1-hu Fc were measured by surface plasmon resonance (SPR) technology using Biacore T200 instrument (GE Healthcare),” (see paragraphs 0402-0403). CBL teaches methods of administering this antibody to treat cancer and disease (neurological disease; see claims 33, 34, and 36-37 of CBL). CBL teaches an embodiment, the 1.1a Humabody VH of Table 15, which has a binding affinity for human PD-1 of 6.76X10^-10, which is 0.676nM. CBL teaches that, “In another aspect of the present invention, there is provided a pharmaceutical composition comprising a binding agent or composition according to the present invention and optionally a pharmaceutically acceptable carrier,” (see paragraph 0259).
Bernett (US 20180127501 A1; as cited on the 04/03/2024 IDS) teaches a bispecific antibody that binds PD-1 (see claims 1, 3, 5-6, and 15). Bernett further teaches that:
“Specific binding for a particular antigen or an epitope can be exhibited, for example, by an antibody having a KD for an antigen or epitope of at least about 10−4 M, at least about 10−5 M, at least about 10−6 M, at least about 10−7 M, at least about 10−8 M, at least about 10−9 M, alternatively at least about 10−10 M, at least about 10−11 Mat least about 10−12 M, or greater, where KD refers to a dissociation rate of a particular antibody-antigen interaction,”
(see paragraph 0189). Note that this is a 10 fold increase in affinity as compared to that of Nivolumab as taught by Ono, as discussed above. Bernett further teaches:
“ In further aspects, the invention provides heterodimeric antibodies comprising: a) a first heavy chain comprising a first Fc domain, an optional domain linker and a first antigen binding domain comprising an scFv that binds a first antigen; b) a second heavy chain comprising a heavy chain comprising a heavy chain constant domain comprising a second Fc domain, a hinge domain, a CH1 domain [teaching a CH1 region] and a variable heavy domain; and c) a light chain comprising a variable light domain and a light chain constant domain [teaching a CL region]; wherein said variable heavy domain and said variable light domain form a second antigen binding domain that binds a second antigen, wherein one of said first and second antigen binding domains binds human ICOS and the other binds human PD-1,”
(see paragraph 0012).
Fessas et al (A molecular and preclinical comparison of the PD-1-targeted T-cell checkpoint inhibitors nivolumab and pembrolizumab. Semin Oncol. 2017 Apr;44(2):136-140. doi: 10.1053/j.seminoncol.2017.06.002; as cited on the 04/03/2024 IDS) teaches that:
“Crystal structures of the PD-1 ectodomain in complex with the Fab fragments of nivolumab and pembrolizumab have shown that there is a significant overlap between the epitopes of both of these mAbs with the PD-L1 binding site. Nivolumab binds PD-1 by using the N-terminal extension, FG and BC loops as a platform for binding. The binding affinity is heavily dependent on the N terminal extension, which is not involved in PD-L1 recognition, while the overlapping binding surface shared by the VL region of the antibody and PD-L1 resides mostly on the FG loop. On the other hand, the interaction of pembrolizumab with PD-1 is heavily dependent on the flexible C′D loop of PD-1, which is not involved in the interaction with PD-L1. However, its interaction also with the C and C′ strands of PD-1 ensure that it competes with the binding of PD-L1. In addition, binding of either of these antibodies induces small conformational changes in the flexible BC and FG loops of PD-1, which are incompatible with PD-L1 binding. These structural features suggest that both these antibodies have a similar mechanism of action whereby they competitively inhibit PD-L1 binding by direct occupancy and steric blockade of the PD-L1 binding site,”
(see paragraph 2 of section 3).
Geuijen (US 20200325227 A1; as cited on the 04/03/2024 IDS) teaches, that “bivalent monospecific antibodies that comprise two of said variable domains that bind PD-1, and bivalent monospecific antibodies that comprise two of said variable domains that bind PD-L1,” are known in the art and discloses that their invention was compared to such bivalent, monospecific antibodies. Geuijen further teaches that:
“In some embodiments, an antibody of the invention is an IgG, preferably a full length IgG. Full length IgG antibodies are preferred because of their typically favorable half-life and the desire to stay as close to fully autologous (human) molecules for reasons of immunogenicity. In some embodiments, an antibody of the invention is a full length IgG1, a full length IgG2, a full length IgG3 or a full length IgG4 antibody,”
(see paragraph 0268).
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ASHLEY GAO whose telephone number is (571) 272-5695. The examiner can normally be reached on Monday- Friday 8-5pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s
supervisor, Gregory Emch can be reached on (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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/Ashley Gao/
Examiner, Art Unit 1678
/GREGORY S EMCH/Supervisory Patent Examiner, Art Unit 1678
Prosecution Insights