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 .
Election/Restrictions
Applicant’s election without traverse of Group I and the species of (A) TRBV5-5 as a species of TRBV polypeptide, (a) SEQ ID NOs: 1-6 as the VH and VL CDRs corresponding to election (A); (B) CD3 as a species of T cell co-receptor, (b) SEQ ID NOs: 17-22 as the VH and VL CDRs corresponding to election (B); and (C) acute lymphoblastic leukemia (ALL) as a species of T cell cancer, in the reply filed on 17 June 2026 is acknowledged. Claims 1-7 and 12-15 read on the elected species.
Claims 8-11 and 16-26 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected inventions, there being no allowable generic or linking claim.
Claims 1-7 and 12-15 are examined upon their merits.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. This application is the national stage entry of PCT/US2021/061453 filed on 1 December 2021, and claiming the benefit of US Provisional Application No. 63/119,753 filed on 1 December 2020.
Claims 1-7 and 12-15 have an effective US filing date of 1 December 2020.
Claim Interpretation
While not rising to the level of being indefinite under 35 U.S.C. 112(b), instant claims 5-7 recite: a light chain including a VL CDR1 having an amino acid sequence set forth in SEQ ID NO:1, a VL CDR2 having an amino acid sequence set forth in SEQ ID NO:2, and a VL CDR3 having an amino acid sequence set forth in SEQ ID NO:3; and a heavy chain including a VH CDR1 having an amino acid sequence set forth in SEQ ID NO:4, a VH CDR2 having an amino acid sequence set forth in SEQ ID NO:5, and a VH CDR3 having an amino acid sequence set forth in SEQ ID NO:6; wherein said light chain comprises an amino acid sequence set forth in SEQ ID NO:7, and wherein said heavy chain comprises an amino acid sequence set forth in SEQ ID NO:8; and, wherein said light chain comprises an amino acid sequence set forth in SEQ ID NO:38, and wherein said heavy chain comprises an amino acid sequence set forth in SEQ ID NO:39. The phrase “comprises an amino acid sequence set forth in…” reads upon any two or more continguous amino acids within the sequence claimed. Thus, this language is far broader than, for example, language along the lines of “comprises the amino acid sequence set forth in …” and opens the claims up to more prior art references.
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 1-7 and 12-15 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.
The Federal Circuit (Federal Circuit) decided in Amgen v. Sanofi, 872 F.3d 1367 (Fed. Cir. 2017), that disclosure of an antigen fully characterized by its structure, formula, chemical name, physical properties, or deposit in a public depository does not, without more, provide an adequate written description of an antibody claimed by its binding affinity to that antigen, even when preparation of such an antibody is routine and conventional. See Amgen Inc. v. Sanofi, 872 F.3d 1367, 1378, 124 USPQ2d 1354, 1361 (Fed. Cir. 2017)("knowledge of the chemical structure of an antigen [does not give] the required kind of structure-identifying information about the corresponding antibodies"); see also Centocor Ortho Biotech, Inc. v. Abbott Labs., 636 F.3d 1341, 1351-52, 97 USPQ2d 1870, 1877 (Fed. Cir. 2011)(patent disclosed the antigen the claimed antibody was supposed to bind, but did not disclose any antibodies with the specific claimed properties). See MPEP 2163.II.A.3(a).
In view of the Amgen decision, the instant claims fail to meet the requirements for disclosure because the antibody is described solely by the antigens to which the bispecific molecule binds –a first antigen binding domain that can bind a T cell receptor β chain variable (TRBV) polypeptide; and a second antigen binding domain that can bind a T cell co-receptor polypeptide (claim 1); or the instantly-elected TRBV5-5 polypeptide (claims 3 and 4).
Additionally, as stated in the section on Claim Interpretation above, the instant claims read upon a vast genus because “comprises an amino acid sequence set forth in…” reads upon any two or more continguous amino acids within the sequence claimed (claims 5-7). As such the specification fails to disclose those 2 or more contiguous residues from each sequence that fulfills the functional requirements of the claims. Nor is there a representative number of species of two or more continguous amino acids within each sequence that fulfill the binding requirements of the claims.
The CAFC stated: 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. It is expected that all of the heavy and light chain CDRs in their proper order and in the context of framework sequences which maintain their required conformation, are required in order to produce a protein having antigen-binding function and that proper association of heavy and light chain variable regions is required in order to form functional antigen binding sites.
Therefore, in view of the current case law, Claims 1-4 and 12-15 are rejected since they fail to provide all 6 CDR structures.
Claims 1-7 and 12-15 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a bispecific molecule comprising a light chain including a VL CDR1 having the amino acid sequence set forth in SEQ ID NO:1, a VL CDR2 having the amino acid sequence set forth in SEQ ID NO:2, and a VL CDR3 having the amino acid sequence set forth in SEQ ID NO:3; and a heavy chain including a VH CDR1 having the amino acid sequence set forth in SEQ ID NO:4, a VH CDR2 having the amino acid sequence set forth in SEQ ID NO:5, and a VH CDR3 having the amino acid sequence set forth in SEQ ID NO:6 (claim 5); wherein said light chain comprises the amino acid sequence set forth in SEQ ID NO:7, and wherein said heavy chain comprises the amino acid sequence set forth in SEQ ID NO:8 (claim 5); and, wherein said light chain comprises the amino acid sequence set forth in SEQ ID NO:38, and wherein said heavy chain comprises the amino acid sequence set forth in SEQ ID NO:39, does not reasonably provide enablement for any other bispecific molecule comprising a first polypeptide comprising a first antigen binding domain that can bind a T cell receptor p chain variable (TRBV) polypeptide; and a second polypeptide comprising a second antigen binding domain that can bind a T cell co-receptor polypeptide. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
In AMGEN INC. ET AL. v. SANOFI ET AL. (No. 21-757, decided May 18, 2023), the Supreme Court held that Amgen was not enabled for “the entire genus” of antibodies that (1) “bind to specific amino acid residues on PCSK9,” and (2) “block PCSK9 from binding to [LDL receptors]” (872 F. 3d 1367, 1372) even though Amgen identified the amino acid sequences of 26 antibodies that perform these two functions.
The case law applies to the instant claims which require a genus of bispecific molecules that comprise a first polypeptide comprising a first antigen binding domain that can bind a T cell receptor p chain variable (TRBV) polypeptide; and a second polypeptide comprising a second antigen binding domain that can bind a T cell co-receptor polypeptide. Depending claims recite the TRBV polypeptide is specifically the instantly-elected TRBV5-5. Thus, similar to the claims in Amgen, the instant claims encompass an “entire genus” of bispecific antibodies that are merely defined by functional language and an antigen to which it binds. Additionally, as stated in the section on Claim Interpretation above, the instant claims read upon a vast genus because “comprises an amino acid sequence set forth in…” reads upon any two or more continguous amino acids within the sequence claimed (claims 5-7). As such, the specification fails to disclose those 2 or more contiguous residues from each sequence that fulfills the functional requirements of the claims. Nor is there a representative number of species of two or more continguous amino acids within each sequence that fulfill the binding requirements of the claims, thus the claims are not enabled for the full scope of what is encompassed by the breadth of the claims.
In contrast to the breadth of the claims the specification teaches a single discrete bispecific antibody that has the light and heavy chain sequences as stated in claims 5-7.
Regarding the predictability in the art, in Amgen, the Supreme Court has stated:
“An antibody’s structure does much to dictate its function—its ability to bind to an antigen and, in some instances, to block other molecules in the body from doing the same. ‘For an antibody to bind to an antigen, the two surfaces have to fit together and contact each other at multiple points.’ Id., at 11. But just because an antibody can bind to an antigen does not mean that it can also block. To bind and block, the antibody must establish a sufficiently broad, strong, and stable bond to the antigen. See ibid. Different antibodies have different binding and blocking capacities based on the amino acids that compose them and their three-dimensional shapes. See id., at 11–12.
Despite recent advances, aspects of antibody science remain unpredictable. For example, scientists understand that changing even one amino acid in the sequence can alter an antibody’s structure and function. See id., at 14. But scientists cannot always accurately predict exactly how trading one amino acid for another will affect an antibody’s structure and function. Ibid.”
Given that structure is essential to function; and given the unpredictability within the art with respect to creating antibodies. A person having ordinary skill in the art would have to perform further experimentation in order to make the bispecific molecules encompassed by the genus of the claims. Given the nature of the invention, a skilled artisan would have to make multiple bispecific molecules against any T cell receptor beta chain variable (TRBV) and against any T cell co-receptor, then validate their specific binding function in order to make the invention with a reasonable expectation of success. This amount of experimentation goes beyond what is considered “a reasonable degree of experimentation” and constitutes undue further experimentation in order to enable the invention commensurate in scope with the breadth of the claims.
For all of these reasons, the specification does not enable the claims, and Claims 1-4 and 12-15 are rejected under 35 U.S.C. 112(a).
Conclusion
No claim is allowed at this time.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to STACEY NEE MACFARLANE whose telephone number is (571)270-3057. The examiner can normally be reached M-F 7:30-5 (EST) & Sat. A.M..
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/STACEY N MACFARLANE/Examiner, Art Unit 1675
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