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
Applicant’s election without traverse of Group I, claims 1-3, 6, 7, 20, 23, 29, 32, and 73 in the reply filed on December 22, 2025 is acknowledged.
Applicant’s election without traverse of species, a specific anti-B7-H4 antibody or antigen-binding fragment thereof comprising the sequences of CDR1H, CDR2H and CDR3H comprising SEQ ID NOS: 16, 17, and 18, the sequences of CDR1L, CDR2L and CDR3L comprising SEQ ID NOS: 70, 71, and 72, the sequence of VH comprising SEQ ID NO: 15 and the sequence of VL comprising SEQ ID NO: 69, in the reply filed on December 22, 2025 is also acknowledged.
Claims 4, 5, 8-19, 21, 22, 24-28, 30, 31, 33, and 34 were previously canceled.
Claims 35, 36, 66-68, 74, 79, 80, 95 and 96 has been canceled in the amended claims filed on December 22, 2025.
Claims 1, 3, and 23 have been amended.
Claims 1-3, 6, 7, 20, 23, 29, 32 and 73 are pending and under consideration.
It is noted that prior art does not teach or suggest the anti-B7-H4 antibody or antigen-binding fragment thereof comprising the sequences of CDR1H, CDR2H and CDR3H comprising SEQ ID NOS: 16, 17, and 18, the sequences of CDR1L, CDR2L and CDR3L comprising SEQ ID NOS: 70, 71, and 72; the sequence of VH comprising SEQ ID NO: 15 and the sequence of VL comprising SEQ ID NO: 69 (the elected species). Therefore, search is extended to other species encompasses by the pending claims. It acknowledged that prior art does not teach the antibodies: 3F2/3F2, 3F2/50A10, 3F2/49A2 (3F2 and derivatives in Table 5); 9D11/9D11, 9D11/67E12, 9D11/67C6, 9D11/67C3, 9D11/68F5, 9D11/67G3, 9D11/67H9 (9D11 and derivatives in Table 7); 39A11/39A11, 39A11/57H3, 39A11/57G8, 39A11/56A9, 39A11/56H7, 39A11/62F9 (39A11 and derivatives in Table 9); 1D3/ID3, 1D3/45A2, 1D3/47B2 (1D3 and derivatives in Table 17). However, the pending claims encompass variants which are not supported by the specification (see 112(a) rejection below).
Priority
It is acknowledged that this application claims the benefit of priority to U.S. Provisional Patent Appl. No. 63/284,937 filed December 1, 2021. The priority date has been established as December 1, 2021 for the pending claims.
Information Disclosure Statement
The Information Disclosure Statement filed on 06/20/2023 has been considered and entered by examiner.
Specification
The disclosure is objected to because of the following informalities: The current application was filed after July 1, 2022, thus the WIPO Standard ST.26, Sequence Listing in XML format, applies to sequence disclosures. See 37 CFR § 1.831. An ST.26 Sequence Listing in XML must not include any sequences having fewer than 10 specifically defined nucleotides, or fewer than 4 specifically defined amino acids. See 37 CFR § 1.831(j).
The specification filed 11/29/2022 refers SEQ ID NO: 74 at least in Table 5, Table 16 and Table 20; SEQ ID NO: 85 at least in Table 5, Table 17 and Table 20; SEQ ID NO:112 at least in Table 8, Table 18 and Table 20; SEQ ID NO:134, SEQ ID NO:135 at least in Table 9, Table 19 and Table 20; SEQ ID NO:176 at least in Table 20 and Table 24; and SEQ ID NO:182 at least in Table 20 and Table 24. These sequences are replaced with “000” in the Sequence Listing in XML because the sequences are less than 4 amino acid sequences. These SEQ ID NOS in the specification should be deleted and replaced with correct sequences because the Sequence Listing in XML does not contain the short sequences.
Appropriate correction is required.
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 1-3, 6, 7, 20, 23, 29, 32 and 73 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 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. This is a WRITTEN DESCRIPTION rejection.
The claims are drawn to an anti-B7-H4 antibody, or antigen-binding fragment thereof, wherein the antibody, or antigen-binding fragment thereof, comprises a heavy chain variable region and a light chain variable region, wherein each of the heavy chain and the light chain variable regions comprise a CDR1, CDR2, and CDR3, and wherein: a. CDR1H comprises SEQ ID NO:16, CDR2H comprises SEQ ID NO:17, CDR3H comprises SEQ ID NO:18, and …, or vi. CDR1L comprises SEQ ID NO:131, CDR2L comprises SEQ ID NO:132,and CDR3L comprises SEQ ID NO:133.
By reciting “the heavy chain variable region comprises … a sequence that is at least 90% identical to SEQ ID NO: XX” and “the light chain variable region comprises … a sequence that is at least 90% identical to SEQ ID NO: XX” (see claim 3), the claims encompass an enormous number of variants of recited heavy chain variable regions and light chain variable regions. In addition, by reciting “comprise at least one modification in the CH3 domains of the first and the second heavy chain constant region causing heterodimerization” (see claim 29), the claims encompass a broad genus of modifications (known or yet to be discovered) in CH3 domains of heavy chain which could cause heterodimerization. This would generate an even larger combinations of variable domain variants and Fc variants which might have different two- and/or three-dimensional structures. The specification discloses 3F2, 3F2/50A10, 3F2/49A2 (3F2 and derivatives in Table 5); 9D11, 9D11/67E12, 9D11/67C6, 9D11/67C3, 9D11/68F5, 9D11/67G3, 9D11/67H9 (9D11 and derivatives in Table 7); 39A11, 39A11/57H3, 39A11/57G8, 39A11/56A9, 39A11/56H7, 39A11/62F9 (39A11 and derivatives in Table 9); 1D3, 1D3/45A2, 1D3/47B2 (1D3 and derivatives in Table 17), which comprise the recited HCDRs and LCDRs. However, the specification does not disclose any variant of heavy chain or light chain variable region which has the similar properties as the antibodies disclosed in the specification. In addition, the specification discloses several modification in the CH3 domain causing heterodimerization, see claim 32, paragraphs [0106] and [0673-0677] of the instant publication US 2023/0312724 A1. However, these disclosed modifications do not tell other modifications which could cause antibody heterodimerization.
Vas-Gath, Inc. v" Mahurkar, 19 USPQ2d 1111, makes clear that "to satisfy the written description requirement, an 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, and that the invention, in that context, is whatever is now claimed".
Regarding up to 10% variations to recited SEQ ID NOS, although the claims recite CDRs 1H-3H and CDRs 1L-3L for the B7-H4 antibody or antigen-binding fragment thereof, it is well known that in the variable domain of an antibody, even outside the CDRs, can significantly impact antibody binding. Mutations in the framework regions (non-CDR areas) can alter the structure and dynamics of the antibody, affecting its ability to bind to its target antigen. For example, even single amino acid change in antigen-distal framework position can result in different conformational space and potentially different binding functions, see § Significance on page E486 of Koenig (Koenig et al., PNAS, E486-E495, Publication Date: 01/05/2017).
Regarding claimed “modifications causing heterodimerization”, the claims identify the modifications by function only. The specification and prior art disclose some modifications (see claim 32, paragraphs [0106] and [0673-0677] of the instant publication US 2023/0312724 A1) which have the claimed function. However, the specification and prior art have not established the relationship between the claimed functions and the structure of the antibody, thus, the modifications disclosed by the instant specification or prior art would not teach other modifications at different positions which could possibly cause heterodimerization.
In additions, the claims encompass all types of antibodies e.g. IgG, IgE, IgM, IgA; all types of modification including mutations. First, it is known that different types of heavy chains have different length and structure. IgG and IgE have different structure and different amino acid sequences in CH3 region, as evidenced by Fig. 1 of Wurzburg (Wurzburg et al., Immunity, Vol. 13, 375-385, Publication Date: September 2000). In addition, IgE-Fc region is more flexible than IgG-Fc region (§ Analysis of IgE- and IgG-Fc Conformational Flexibility), and interactions at the IgE-Fc and IgG-Fc domain interfaces are different (Fig. 4). One of ordinary skill in the art would recognize that the same modifications (e.g. substitution) would have different impact on structure or binding property of IgE and IgG antibodies.
Taken together, the antibodies disclosed by the instant specification do not provide sufficient written description support for the broadly claimed antibody or antigen-binding fragments thereof.
Furthermore, the written description provision of 35 USC § 112 is severable from its enablement provision; and adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method for isolating it. Fiers v. Revel, 25 USPQ2d 1601, 1606 (CAFC 1993). And Amgen Inc. v. Chugai
Pharmaceutical Co. Ltd., 18 USPQ2d 1016. The Guidelines for Examination of Patent
Applications under the 35 USC §112 paragraph 1, "Revision 1" of Written Description
Requirement (66 FR 1099-1111, March 25, 2008) state, "[p]ossession may be shown in a variety of ways including description of an actual reduction to practice, or by showing the invention was 'ready for patenting' such as by disclosure of drawings or structural chemical formulas that show that the invention was complete, or by describing distinguishing identifying characteristics sufficient to show that the Applicant was in possession of the claimed invention (Id. At 1104). Moreover, an adequate written description of the claimed invention must include sufficient description of at least a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics sufficient to show that Applicant was in possession of the claimed genus. However, factual evidence of an actual reduction to practice has not been disclosed by Applicant in the specification; nor has Applicant shown the invention was "ready for patenting" by disclosure of drawings or structural chemical formulas that show that the invention was complete; nor has the
Applicant described distinguishing identifying characteristics sufficient to show that
Applicant were in possession of the claimed invention at the time the application was filed.
The ordinary artisan could reasonably conclude based on a survey of the data shown in the instant specification in support of the breadth and scope of the instant claimed antibodies that Applicants were not in possession of the innumerable variants for the claimed antibodies (including an enormous number of variants of recited heavy chain variable regions and light chain variable regions and/or a broad genus of modifications causing heterodimerization). Taken together, the instant specification has not provided a sufficient description for the broad genus of antibodies encompassed by the claims.
Related Prior Art
Bao (Bao et al., EP 3753951 A1, Publication Date: 12/23/2020, IDS) teaches anti-B7-H4 antibody or antigen-binding fragment thereof to human B7-H4 receptor, chimeric antibodies and humanized antibodies ([0001]). Examples 1 and 2 teaches specific sequences for various anti-B7-H4 antibodies ([0092]). Example 9 teaches anti-tumor activity of humanized B7-H4 antibody: 1C9. Example 10 teaches antibody 1C9 and 2G6 enhancing proliferation of T cells. However, Bao does not teach the specific CDRs recited by the instant claim 1.
Leong (Leong et al., WO 2016/040724 A1, Publication Date: 03/17/2016, IDS). Leong teaches humanized anti-B7-H4 antibodies (examples, in particular section E, [0490] and [0491]). Leong teaches antibodies which bind to human B7-H4 in nanomolar range (pages 156-157, Fig. 12). Leong teaches that antibodies are cross-reactive to human, mouse, rat and cynomolgus species (section E1, pages 155-156, Fig. 11). Leong teaches antibodies binding to Ig-V domain of B7-H4 (page 157-158, Fig. 4a). However, Leong does not teach the specific CDRs recited by the instant claim 1.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHENG LU whose telephone number is (571)272-0334. The examiner can normally be reached Monday-Friday 8-5.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Samira Jean-Louis can be reached at (571)270-3503. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/CHENG LU/ Examiner, Art Unit 1642