Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
Restriction/Election
1. Applicant’s election without traverse of Group (claims 11-12, 14-15, 17, and 22-30) in the reply filed on 08/25/2026 is acknowledged. Applicant also elected the following species:
(i) a bispecific antibody wherein the first protein functional region targeting PD-1 is an immunoglobulin, and the second protein function region targeting CTLA4 is a single chain antibody;
(ii). an anti-VEGFR2 monoclonal antibody, wherein the anti-VEGFR2 monoclonal antibody comprises HCDR1-HCDR3 in a heavy chain variable region set forth in SEQ ID NO: 50 and LCDR1-LCDR3 in a light chain variable region set forth in SEQ ID NO: 52; preferably HCDR1-HCDR3 are set forth in SEQ ID NOs: 53-55, and LCDR1- LCDR3 are set forth in SEQ ID NOs: 56-58, respectively;
(iii). an anti-CTLA4-anti-PD-1 bispecific antibody comprising a first protein functional region targeting PD 1 comprising HCDR1-HCDR3 set forth in SEQ ID NOs: 27-29, respectively and LCDR1-LCDR3 set forth in SEQ ID NOs: 30-32, respectively, a heavy chain variable region set forth in SEQ ID NO:18 and a light chain variable region set forth in SEQ ID NO:20 which comprises the above CDRs sequences, respectively, a heavy chain sequence set forth in SEQ ID NO:40 and a light chain sequence set forth in SEQ ID NO:24; and a second protein functional region targeting CTLA4 comprising HCDR1-HCDR3 set forth in SEQ ID NOs: 33-35, respectively and LCDR1-LCDR3 set forth in SEQ ID NOs: 36-38, respectively, a heavy chain variable region set forth in SEQ ID NO:43 and a light chain variable region set forth in SEQ ID NO:44 which comprise the above CDRs sequences, respectively, a heavy chain sequence set forth in SEQ ID NO:70 and the light chain sequence set forth in SEQ ID NO:72.
(iv). paclitaxel.
(v). gastric cancer.
2. Claims 11-17 and 22-30 are pending. Claims 11-12, 14-15, 17, and 22-30 are currently under consideration. Claims 13, 16, and 18-21 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention.
Information Disclosure Statement
3. The information disclosure statement filed on 09/14/2026, 06/23/2025,12/10/2024, and 06/21/2024 has been considered by the Examiner and an initialed copy of the form PTO-1449 is attached to this communication.
Drawings
4. The drawing filed on 10/12/2023 are accepted by the examiner.
Claim Rejections[Symbol font/0xBE]35 USC § 101
5. 35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
6. Claim 12 is rejected under 35 U.S.C. 101 because the claimed recitation of a use, without setting forth any steps involved in the process, results in an improper definition of a process, i.e., results in a claim which is not a proper process claim under 35 U.S.C. §101. See for example Ex parte Dunki, 153 USPQ 678 (Bd.App. 1967) and Clinical Products, Ltd. v. Brenner, 255 F. Supp. 131, 149 USPQ 475 (D.D.C. 1966).
Claim Rejections[Symbol font/0xBE]35 USC § 112 (a)
7. The following is a quotation of the first paragraph of 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.
8. Claims 11-12, 14-15, 17, and 22-30 are rejected under 35 U.S.C. 112(a), 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 at the time the application was filed, had possession of the claimed invention.
To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116.
Claims 11-12, 14-15, 17, and 22-30 are drawn to a pharmaceutical composition for treating a tumor comprising an effective amount of an anti-CTLA4-anti-PD-1 bispecific antibody and an anti-VEGFR2 monoclonal antibody or an antigen-binding fragment thereof. The claims recite “functional variants thereof” and “wherein a sequence of the functional variant has at least 60%, 70%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%,91%, 92%,93%,94%, 95%,96%, 97%, 98%, or at least 99% homology to the corresponding sequence”. Thus, the claims encompass a huge genus of anti-CTLA4-anti-PD-1 bispecific antibodies and a genus of anti-VEGFR2 monoclonal antibodies without a definitive structure. However, the instant disclosure is insufficient to support the broad genus of anti-CTLA4-anti-PD-1 bispecific antibodies and anti-VEGFR2 monoclonal antibodies.
For each claim drawn to a genus, MPEP §2163 II.A.3(a) ii) (page 2100-189) states, “The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice (see i)(A), above), reduction to drawings (see i)(B), above), or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus (see i)(C), above). See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406”.
It is well established in the art that the formation of an intact antigen binding site of an antibody routinely requires the association of the complete heavy and light chain variable regions of a given antibody. It is expected that proper association of heavy and light chain variable regions is required in order to form a functional antigen binding site (Paul, Fundamental Immunology, 3rd Edition, 1993, pages 292-295; in particular page 293, column 1, lines 3-8; column 1, line 31 to column 2, line 9; column 2, lines 27-30). Vajdos et al. teach that amino acid sequence and conformation of each of the CDRs of the heavy and light chains is critical for maintaining the antigen binding specificity and affinity which is characteristic of the parent immunoglobulin (J. Mal. Biol. 320:415-428, 2002; in particular page 416).
Furthermore, the prior art does not provide compensatory structural or correlative teachings sufficient to enable one of skill to identify what other anti-CTLA4-anti-PD-1 bispecific antibodies or anti-VEGFR2 monoclonal antibodies might be. Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics (a set of six intact CDRs) , the specification does not provide adequate written description of the genus of the recited anti-CTLA4-anti-PD-1 bispecific antibodies or anti-VEGFR2 monoclonal antibodies.
Claim Rejections[Symbol font/0xBE]35 USC § 112 (b)
9. The following is a quotation of the second paragraph of 35 U.S.C. 112:
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.
10. A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c).
In the present instance, claim 11 recites the broad recitation “a tumor” in line 1 and the claim also recites “(particularly a malignant tumor)” in line 1, which is the narrower statement of the range/limitation. Likewise, claims 11, 12, 14-15, 17, 28, and 30 recite the terms “preferably”, “optionally”, “e.g”, “such as”, and “particularly” which have the same issue.
The claim is considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claim.
11. Claim 27 is rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Claim 27 is indefinite because it recites “wherein the numbers of the first and second protein functional regions are each independently 1, 2, or more”. There is no upper limit for the first and second protein functional regions.
Claim Rejections under 35 USC § 103(a)
12. The following is a quotation of 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
13. Claims 11-12, 14-15, 17, and 22-30 are rejected under 35 U.S.C. 103(a) as being unpatentable over CN 1123002386 A (Pub. Date: Feb. 2, 2021) in view of CN 106188296 A (Dec. 7, 2016) and CN 104971253 A (Oct. 14, 2015).
CN 1123002386 A teaches a pharmaceutical composition for treating a tumor comprising the anti-CTLA4-anti-PD-1 bispecific antibody recited in the instant claims (see, e.g., claims 1-29; Abstract) and a chemotherapeutic drug (claim 24; paragraphs [0139]-[01405).
CN 1123002386 A does not teach the composition comprising an anti-VEGFR2 monoclonal antibody.
CN 106188296 A teaches the anti-VEGFR2 monoclonal antibody recited in the instant claims, which serves as an anti-tumor drug (see, e.g., claims 1-11; Abstract).
It would have been obvious to one having ordinary skill in the art at the time the invention was made to make a pharmaceutical composition for treating a tumor comprising the anti-CTLA4-anti-PD-1 bispecific antibody taught by CN 1123002386 A and the anti-VEGFR2 monoclonal antibody taught by CN 106188296 A with a reasonable expectation of success. One would have been motivated to do so because CN 104971253 A teaches the combined use of an anti-CTLA4-anti-PD-1 bispecific antibody with anti-VEGFR2 monoclonal antibody for tumor treatment (paragraph [0040]).
Claim Rejections[Symbol font/0xBE] Nonstatutory Obviousness-Type Double Patenting
14. Basis for nonstatutory 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. See 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);and, 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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/ guidance/eTD-info-I.jsp.
15. Claims 11-12, 14-15, 17, and 22-30 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 34, 37-46, 52-53, and 58 of copending Application No. 17/630,467 in view of CN 106188296 A (Dec. 7, 2016) and CN 104971253 A (Oct. 14, 2015). Although the conflicting claims are not identical, they are not patentably distinct from each other for the following reasons.
Claims 34, 37-46, 52-53, and 58 of copending Application No. 17/630,467. are drawn to a pharmaceutical composition comprising an anti-CTLA4-anti-PD-1 bispecific antibody, which is identical to the anti-CTLA4-anti-PD-1 bispecific antibody recited in the instant claims.
CN 106188296 A teaches the anti-VEGFR2 monoclonal antibody recited in the instant claims, which serves as an anti-tumor drug (see, e.g., claims 1-11; Abstract).
It would have been obvious to one having ordinary skill in the art at the time the invention was made to make a pharmaceutical composition for treating a tumor comprising the anti-CTLA4-anti-PD-1 bispecific antibody and the anti-VEGFR2 monoclonal antibody taught by CN 106188296 A with a reasonable expectation of success. One would have been motivated to do so because CN 104971253 A teaches the combined use of an anti-CTLA4-anti-PD-1 bispecific antibody with anti-VEGFR2 monoclonal antibody for tumor treatment (paragraph [0040]).
This is a provisional nonstatutory double patenting rejection.
Conclusion
16. No claims are allowed.
Advisory Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Ruixiang Li whose telephone number is (571) 272-0875. The examiner can normally be reached on Monday through Friday from 8:30 am to 5:00 pm. If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Vanessa Ford, can be reached on (571) 272-0857. The fax number for the organization where this application or proceeding is assigned is (571) 273-8300.
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/RUIXIANG LI/Primary Examiner, Art Unit 1674
October 7, 2026
