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 III in the reply filed on31 May 2024is acknowledged. The Species Election requirement, with respect to Group III has been withdrawn. All species within Group III, claims 12-18, have been rejoined.
Claims 1-11, 19 and 23 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected inventions, there being no allowable generic or linking claim.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 12-18 are examined upon their merits.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
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.
Claims 12-18 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 12 recites an “antibody format”. There is no explicit definition for this term in the specification, nor is there a common language definition within the art. Absent a definition, it is unclear what is encompassed by this claim limitation.
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 12-18 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.
In making a determination of whether the application complies with the written description requirement of 35 U.S.C. 112, first paragraph, it is necessary to understand what Applicant has possession of and what Applicant is claiming. Claim 12 recites two antibodies each comprising 6 CDR sequences set forth in discrete amino acid sequences, however, each CDR further encompasses “or a variant thereof”. Additionally, the claim recites an antibody comprising either a heavy chain as claimed OR a light chain as claimed. Thus, the claims comprise a genus of antibodies comprising altered CDR sequences and there is no adequate written description for which residues within the CDRs may be altered in the claimed variants. Additionally, the claim encompasses single chain antibody fragments, which are not described by the instant specification as functional. Claim 17 recites heavy and light chains as defined by the SEQ ID NOs of the claims “having at least about 90% identity thereto”, which encompasses sequences having up to 10% altered residues. Claim 18 recites, “an amino acid sequence having at least about 95%, or 97%, or 98% identity with SEQ ID NO: 17 and/or SEQ ID NO. 21 of SEQ ID NO: 25 and/or SEQ ID NO: 29.” First, the “an amino acid sequence” language reads upon any two or more consecutive amino acids within the sequence and therefore encompasses a vast array of amino acid sub-sequences. Secondly, even if claim language is altered to recite “the amino acid sequence…”, claim 18 would still allow for 2% and up to 5% of the sequence “having one or more amino acid mutations (e.g., substitutions or deletions)” (specification pg. 13). Therefore, all of the claims encompass a genus of amino acid sequences that are not defined by definitive structure.
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 MPEP 2163(II)(3)(a)( i)(A), reduction to drawings MPEP 2163(II)(3)(a) (i)(B), 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 MPEP 2163(II)(3)(a) (i)(C). See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
In the instant case, the specification fails to provide adequate written description of any variant CDR sequences that still form a functioning antibody or fragment thereof. There is no description of functional single chain comprising either light or heavy. For the genera recited by Claims 17-18, the specification fails to disclose those 2-10% of residues that may be mutated, substituted or deleted such that the antibody retains functionality. Conversely, the specification fails to identify that portion of antibody residues that must be conserved for antigen binding activity. Regarding the antibodies claimed, the specification teaches only the two discrete antibodies: (1) consisting of the heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 sequence is GYSITSGYY (SEQ ID NO: 18), the heavy chain CDR2 sequence is ISYDGSN (SEQ ID NO: 19), and the heavy chain CDR3 sequence is ARDGTTVVATLAY (SEQ ID NO: 20), and the light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 sequence is SSVSY (SEQ ID NO: 22), the light chain CDR2 sequence is RTS (SEQ ID NO: 23), and the light chain CDR3 sequence is QQYHSYPPT (SEQ ID NO: 24); and (2) the heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 sequence is GYTFASYW(SEQ ID NO: 26), the heavy chain CDR2 sequence is IDPNSGGT (SEQ ID NO: 27), and the heavy chain CDR3 sequence is ARWWDYDYFDY (SEQ ID NO: 28), and the light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 sequence is QSLLNSGNQKRY (SEQID NO: 30), the light chain CDR2 sequence is WAS (SEQ ID NO: 31), and the light chain CDR3 sequence is QNDYNYPLT (SEQ ID NO: 32). Thus, in contrast to what is described within the specification, the claims are drawn to a genus of molecules that is defined merely defined by function (antibody) and the instant specification fails to describe the entire genus of molecules that are encompassed by these claims.
Additionally, the specification fails to provide a representative number of species for the recited genus. As stated, there are no representative examples of antibodies comprising variant CDRs; nor are there representative species of single chain antibodies comprising either a light or heavy chain; nor are there a representative number of species having at least about 90% identity, at least about 95%, or 97%, or 98% identity. Thus, the specification fails to provide adequate description for the genus of antibodies encompassed by the claims or a representative number of species within each of the genera claimed. Therefore, the specification does not provide adequate written description of the claimed genus/genera.
Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. § 112 is severable from its enablement provision (see page 1115).
Claims 12-18 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 two discrete antibodies: (1) consisting of the heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 sequence is GYSITSGYY (SEQ ID NO: 18), the heavy chain CDR2 sequence is ISYDGSN (SEQ ID NO: 19), and the heavy chain CDR3 sequence is ARDGTTVVATLAY (SEQ ID NO: 20), and the light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 sequence is SSVSY (SEQ ID NO: 22), the light chain CDR2 sequence is RTS (SEQ ID NO: 23), and the light chain CDR3 sequence is QQYHSYPPT (SEQ ID NO: 24); and (2) the heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 sequence is GYTFASYW(SEQ ID NO: 26), the heavy chain CDR2 sequence is IDPNSGGT (SEQ ID NO: 27), and the heavy chain CDR3 sequence is ARWWDYDYFDY (SEQ ID NO: 28), and the light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 sequence is QSLLNSGNQKRY (SEQID NO: 30), the light chain CDR2sequence is WAS (SEQ ID NO: 31), and the light chain CDR3 sequence is QNDYNYPLT (SEQ ID NO: 32), does not reasonably provide enablement for any other variant, single chain variable region (either heavy or light), or antibody having at least about 90% identity, or at least about 95%, or 97%, or 98% identity. 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/or 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 recite genera of antibodies: comprising variant CDR sequences; antibodies comprising either a heavy chain or a light chain; antibodies comprising a heavy chain that is at least about 90% identity to the light and heavy chain sequences disclosed; or, antibodies having at least about 95%, or 97%, or 98% identity to the disclosed sequences. Thus, the claims encompass genera of antibodies whereas the claims only disclose those two antibodies recited above.
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 that the Supreme Court has stated that unpredictability remains 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 antibody variants/fragments encompassed by the claims. The amount of experimentation required to create these variant antibodies encompassed by the claims, 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 12-18 are rejected under 35 U.S.C. 112(a).
Allowable Subject Matter
The following two antibodies consisting of:
(1) consisting of the heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 sequence is GYSITSGYY (SEQ ID NO: 18), the heavy chain CDR2 sequence is ISYDGSN (SEQ ID NO: 19), and the heavy chain CDR3 sequence is ARDGTTVVATLAY (SEQ ID NO: 20), and the light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 sequence is SSVSY (SEQ ID NO: 22), the light chain CDR2 sequence is RTS (SEQ ID NO: 23), and the light chain CDR3 sequence is QQYHSYPPT (SEQ ID NO: 24); and
(2) the heavy chain variable region comprising heavy chain CDR1, CDR2, and CDR3 sequences, wherein the heavy chain CDR1 sequence is GYTFASYW(SEQ ID NO: 26), the heavy chain CDR2 sequence is IDPNSGGT (SEQ ID NO: 27), and the heavy chain CDR3 sequence is ARWWDYDYFDY (SEQ ID NO: 28), and the light chain variable region comprising light chain CDR1, CDR2, and CDR3 sequences, wherein the light chain CDR1 sequence is QSLLNSGNQKRY (SEQID NO: 30), the light chain CDR2sequence is WAS (SEQ ID NO: 31), and the light chain CDR3 sequence is QNDYNYPLT (SEQ ID NO: 32), does not reasonably provide enablement for any other variant, single chain variable region (either heavy or light), or antibody having at least about 90% identity, or at least about 95%, or 97%, or 98% identity,
are free of the prior art and would be allowable if corrected for issues under 35 U.S.C. 112(a).
Conclusion
No claim is allowed.
Correspondence
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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