DETAILED ACTION
Election/Restrictions
Applicant’s election of the species “modification at position 238” in the reply filed on 4/30/2026 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)).
Claims 31-45 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 4/30/2026.
Claims 20-30 and 46-51 are pending and will be examined on the merits.
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
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 20-29, 46, 47, 50, and 51 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 IgG bispecific antibody comprising a first heavy chain comprising a first and second polypeptide comprising a CH2 and CH3, wherein there is at least one amino acid modification in the first CH2 or first CH3 region and second CH2 or second CH3 region that decreases the affinity of said IgG bispecific antibody to human Fcy receptor. The instant specification discloses a number of specific point mutations that affect one or more effector functions of the binding protein. Therefore, the structure-to-function correlation is specific to the subset of CH2 or CH3 domains having these specific modifications. The instant claims are broadly drawn to any modification within the first CH2 or CH3 region and second CH2 or CH3 region without providing any guidance as to which amino acids or combinations thereof can be altered to achieve this result. The instant application does not provide adequate written description for any and all bispecific antibodies having a first or second CH2/CH3 with a modification that decreases the affinity of to a human Fcy receptor yet to be discovered. Furthermore, although screening applications are well known in the art to identify these binding antibodies, screening is only a wish or plan for the future invention of undiscovered, unknown polypeptide fragment sequences (the court found in (Rochester v. Searle, 358 F.3d 916, Fed Cir., 2004) that screening assays are not sufficient to provide adequate written description for an invention because they are merely a wish or plan for obtaining the claimed chemical invention). Applicants have not described every species the broadly claimed bispecific antibody structures that function as claimed to adequately describe the entire genus of bispecific antibodies heterodimeric with respect to Protein A binding in the universe. A definition by function does not suffice to define the genus because it is only an indication of what the antibody or protein does, rather than what it is. A description of a genus of antibodies may be achieved by means of a recitation of a representative number of antibodies, defined by sequence, falling within the scope of the genus or of a recitation of structural features common to the members of the genus, which features constitute a substantial portion of the genus. The written description requirement can be met by showing that an invention is complete by disclosure of sufficiently detailed, relevant identifying characteristics ....i.e., complete or partial structure, other physical and/or chemical properties, functional characteristics when coupled with a known or disclosed correlation between function and structure, or some combination of such characteristics. The court found that if the disclosed species only abide in a corner of the genus, one has not described the genus sufficiently to show that the inventor invented, or had possession of, the genus. He only described a portion of it. The specifically elected 238 position accordingly to EU numbering modification does not provide any guidance on the full scope of proteins broadly claimed, and are not representative of nor predictive of any and all other sequences for the broadly claimed genus. No common/shared structure among the polypeptides having the claimed functions as disclosed in the instant specification. However, the instant specification does not describe sufficient representative examples to support the full scope of the claims. Applicants are directed to the recent and relevant decision in AbbVie Deutschland GmbH v. Janssen Biotech, Inc. (Fed. Cir. 2014). The court found that if the disclosed species only abide in a corner of the genus, one has not described the genus sufficiently to show that the inventor invented, or had possession of, the genus. He only described a portion of it. In the instant case, the claims broadly encompass any and all bispecific antibodies having a first CH2 or CH3 and second CH2 or CH3 region modification that decreases the affinity to a human Fcy receptor. Applicants have not established any reasonable structure-function correlation, outside of the elected 238 modification, with regards to binding affinity. Therefore, the claims which do not define the specific modification within the CH2/CH3 region, are rejected for not adequately providing written description for the entire genus instantly claimed.
Claim Rejections - 35 USC § 103
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.
Claim(s) 20-30 and 46-51 are rejected under 35 U.S.C. 103 as being unpatentable over Arathoon et al. (PgPub 2002/0062010) in view of Lazar et al. (PgPub 2009/0010920).
The claims are drawn to an IgG bispecific antibody that comprises a binding specificity toward a tumor antigen (CD20) and a T-cell antigen (CD3) comprising a first and second polypeptide each comprising a CH2 and CH3 region, wherein at least one amino acid sequence modification (elected species position 238) in the first CH2 or CH3 region and the second CH2 or CH3 region decreases the affinity of said IgG bispecific antibody to human Fcy receptor.
Arathoon et al. teach multispecific or bispecific antibodies used for human therapy in redirected cytotoxicity by providing one arm which binds a target tumor cells and another arm which binds a cytotoxic trigger molecule, such as the T-cell receptor or the Fcy receptor. Arathoon et al. disclose engineering to enhance the formation of the desired bispecific antibody from a mixture. Arathoon et al. discloses the invention relates to a method of preparing a heteromultimeric multispecific antibody, the antibody comprising 1) a first polypeptide and a second polypeptide (and additional polypeptides accord to the multiplicity of the antibody) which meet at an interface, wherein the first and additional polypeptides (i.e., a first and second polypeptide) each include a multimerization domain forming an interface between the first and second (or at least one additional) polypeptides, and the multimerization domains promote stable interaction between first and additional polypeptides, and 2) a binding domain in each of the first and at least one additional polypeptide (i.e. a second polypeptide), each binding domain comprising a variable heavy chain and a variable light chain, wherein the variable light chain of the first polypeptide and the variable light chain of the second polypeptide have a common amino acid sequence (see claims of Arathoon). Example 1 of Arathoon et al. disclose CH3 variants to engineer a protuberance-into-cavity (also known as knobs into holes) heteromultimer immunoadhesion. Arathoon et al. does not disclose Fc variants having decreased affinity for Fcy receptors, including the 238 substitution. This deficiency is made up for by Lazar et al.
Lazar et al. teach Fc variants having decreased affinity for FcyRIIb, methods for their generation, Fc polypeptide comprising optimized Fc variants, and methods for using optimized Fc variants. Lazar et al. disclose Fc variants that have at least 1 or more amino acid substitutions as compared to the parent Fc polypeptide, for example the Fc IgG1 region comprising SEQ ID NO: 1. Lazar et al. SEQ ID NO:1 is 100% identical to instantly claimed SEQ ID NO: 1. Lazar et al. additionally discloses the Fc polypeptide may be a parent IgG1, IgA, IgG2a or IgG2b antibody (see Table 10). Lazar et al. further discloses substitutions at positions 238 and 297 (according the EU numbering see paragraph [0020]) as well as several others instantly claimed and recited in instant claims 29, 47, and 49. Lazar et al. disclose “Fc variants of the present invention may confer superior pharmacokinetics on Fc polypeptide therapeutics in animal systems or in humans.” Example 15 of Lazar et al. teach Fc variants for the anti-CD20 antibody rituximab for improving the therapeutic efficacy of anticancer antibodies.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant application, to make a bispecific antibody targeting a tumor antigen such as CD20 and a T-cell receptor such as CD3 having a variant Fc region which decreases binding affinity to Fcy receptors in order to increase half-life based on the teachings of Arathoon et al. and Lazar et al. Arathoon et al. teach bispecific antibodies used for human therapy in redirected cytotoxicity and Lazar et al. teaches Fc variants which can be used to decrease binding affinity to Fcy receptors in order to increase half-life and other pharmacokinetics that may be useful for in vivo therapeutics. Therefore, one of ordinary skill in the art would have reasonable expectation of success, based on the teachings of Arathoon et al. and Lazar et al. to make a more effective therapeutic by using Fc variants with decreased binding affinity to Fcy receptors in a bispecific antibody targeting both a tumor antigen and a T-cell receptor to improve stability and solubility for improved clinical use.
Conclusion
Claims 20-30 and 46-51 are rejected.
No Claim is allowed.
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/Meera Natarajan/Primary Examiner, Art Unit 1643
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