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 .
Election/Restrictions
Applicant’s election without traverse of Group 1 in the reply filed on 10/27/2025 is acknowledged.
Applicant’s species election to the following is confirmed:
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Claims 1, 3-5, 7-9, 11-18, 21-24, and 27 are pending. Claims 7-9, 11, 13-14, and 21-24 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected groups and/or species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 12/27/2025.
Claims 1, 3-5, 12 (as specifically drawn to the species of SEQ ID NO:5), 15-18, and 27 are pending and are currently under consideration.
The species election directed to claim 27 is withdrawn.
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, 3-5, 12, and 15-18 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 broadly drawn to polypeptide complexes comprising, from N-terminus to C-terminus, a Fab domain operably linked to a hinge region, wherein the Fab domain and the hinge region are derived from different IgG isotypes. The broadest reasonable interpretation of Claim 1 encompasses nearly any and all amino acid sequences that have some binding specificity to any antigen in the world. For example, the specification teaches [0093] that “in context of the present invention, the Fab domain may derive from any antibody, especially those that are clinically relevant.”. Regarding the hinge region, the specification teaches [0095] that the hinge region is a flexible linker between the Fab and the Fc of antibody. However, claim 1 does not limit the hinge region to any particular structure. For example, the hinge region could comprise any variant amino acid sequence. This would encompass a huge genus of hinge mutations having any number of insertions, deletions or substitutions. Further such hinge variants could comprise any number of non-naturally occurring amino acid residues. See for example Claim 12, part c.
Thus, the claims broadly encompass a huge genus of polypeptide complexes that could potentially encompass any Fab known or unknown while also comprising a genus of highly variable regions or domains which may or may not function as flexible linkers or hinges.
A description of a genus of may be achieved by means of a recitation of a representative number of species, defined by structure, falling within the scope of the genus. However, the instant specification fails to provide sufficient descriptive information, such as definitive structural or functional features of the claimed genus of Fab domains. For example, the specification teaches [0070] that “Fab” refers to the portion consisting of a single light chain (both variable and constant regions) associating to the variable region and first constant region of a single heavy chain by a disulphide bond in an immunoglobulin (e.g., an antibody) and that this portion is responsible for “various antigen binding”. However, the disclosure fails to describe the common attributes or characteristics that identify members of the genus. For example, the disclosure only teaches two structural species (Anti-Her2 and Anti-CD20- examples 9-11) of polypeptide complexes that encompass Fabs that bind known antigens. Such disclosure is insufficient to describe the large genus. The fundamental factual inquiry is whether the specification conveys with reasonable clarity to those skilled in the art that, as of the filing date sought, inventor was in possession of the invention as now claimed. See, e.g., Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Fed. Cir. 1991). An applicant shows that the inventor was in possession of the claimed invention by describing the claimed invention with all of its limitations using such descriptive means as words, structures, figures, diagrams, and formulas that fully set forth the claimed invention. Lockwood v. Am. Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997). Thus, one of skill in the art would reasonably conclude that the disclosure fails to provide a representative number of Fab species (as part of the polypeptide complex) to describe and enable the genus as broadly claimed.
It is well established in the art that the formation of an intact antigen-binding site generally requires the association of the complete heavy and light chain variable regions of a given antibody, each of which consists of three CDRs which provide the majority of the contact residues for the binding of the antibody to its target epitope. The amino acid sequences and conformations of each of the heavy and light chain CDRs are critical in maintaining the antigen binding specificity and affinity which is characteristic of the parent immunoglobulin.
For example, Vajdos et al. (2002; PTO-892) teach that antigen binding is primarily mediated by the CDRs and that the more highly conserved framework segments which connect the CDRs are mainly involved in supporting the CDR loop conformations although in some cases framework residues also contact the antigen (page 416, left col.). Thus, even minor changes in the amino acid sequences of the heavy and light variable regions, particularly in the CDRs, may dramatically affect antigen-binding function. Additionally, Rudikoff et al. (1982; PTO-892) teaches that the alteration of a single amino acid in the CDR of a phosphocholine-binding myeloma protein resulted in the loss of antigen-binding function (Abstract).
Regarding the genus of hinge regions, it does appear that applicants have support to a sub-genus of hinge domain structures (e.g., Specification, Table 1) such as those presented in Claims 4-5. However, as discussed above, this does not extend to variants of the subgenus which include an unknown number of insertions, deletions, or substitutions or non-naturally occurring amino acids. for a substantial written description. The skilled artisan cannot envision the detailed chemical structure of the encompassed genus of possible domains and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The compound itself is required.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1, 3-4, 12, and 15-17 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by US 2019/0382477 (Drake et al., June 1, 2018).
Drake et al. teach (see page 34) the following polypeptide complex:
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The boxed portions above indicate that this polypeptide complex comprises a hinge region and that the polypeptide is derived from different IgG isotypes, IgG1 and IgG4 isotypes.
Below is a sequence comparison between SEQ ID NO 3175 (Qy) of the prior art and applicant’s SEQ ID NO:23 (Db) which is the heavy chain of the anti-CD20 antibody comprising the IgG1-Fab and the IgG4 Fc [0209]. The boxed region comprises the hinge region of Claim 4.
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While the prior art does not specifically teach all 16 amino acids of SEQ ID NO:5 as claimed in claim 12, it does teach 12/16 amino acids in the hinge region which anticipates a variant as claimed in part (c) of current claim 12.
As to claims 15-17, the prior art polypeptide complex further comprises a human IgG4 Fc polypeptide (constant HC2 and constant HC3) which is operably linked to the hinge region. See paragraphs 0248-0249.
Allowable Subject Matter
Claim 27 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GARY B NICKOL, Ph.D. whose telephone number is (571)272-0835. The examiner can normally be reached M-F 9AM-5:30PM.
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/GARY B NICKOL/Primary Examiner, Art Unit 1643