DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 1-6, 21-23, 25, 28, 80, 81, 83, 86, 89, 93, 106, 107 and 120-125 are pending
Election/Restrictions
Applicant’s election without traverse of Group I in the reply filed on July 7, 2026 is acknowledged. Applicant’s election without traverse of and psoriasis antibody comprising a HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 74, a HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 75, a HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 76, a LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 78, a LC-CDR2 comprising the amino acid sequence of SEQ ID NO: KAS, and a LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 80 in the reply filed June 9, 2026 is acknowledged. New claims 120-125 have been placed in Group III.
Claims 21-23, 25, 28, 83, 86, 93, 106, 107 and 120-125 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on July 7, 2026.
Claims 1-6, 80, 81 and 89 are under examination.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 1-6, 80, 81 and 89 are rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush grouping of the species of antibodies is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons: As disclosed below, the claimed anti- CACNG1 antibodies have distinct CDR amino acid sequences, including the most relevant CDR, HCDR3 (see sequence comparisons below). In addition, the specification discloses that the different anti- CACNG1 antibodies have different binding characteristics (Tables 11.1-4)
Thus, the claimed anti-CACNG1 antibodies have distinct amino acid sequences and likely bind distinct epitopes on CACNG1.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
SEQ ID Nos: 74-75-76 REGN10717
HCDR1 HCDR2 HCDR3
GFTFSTYG IWHDGSDK ARRGIRGTVFDH
SEQ ID Nos: 34-35-36 REGN7660
GLTLSDSA IRNKANRYAT TRNWKIFLFDY
SEQ ID Nos: 42-43-44 REGN9909
GFTFNNYG ISGSGGTT GKGGYCSSSGCRHYGMDV
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.
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.
Claims 1-6, 80, 81 and 89 are rejected under 35 U.S.C. 112(a), 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
The claims are drawn to an antibody or antigen-binding fragment thereof that binds Calcium Voltage-Gated Channel Auxiliary Subunit Gamma 1 (CACNG1), comprising:
(i) a heavy chain variable region (HCVR) that comprises the heavy chain
complementarity determining region 1 (HCDR1), HCDR2, and HCDR3 of an HCVR comprising the amino acid sequence set forth in SEQ ID NO: 1, 9, 17, 25, 33, 41, 49, 57, 65, 73, 81, 89, 97, 105, 113, 121, 129, 137,429, or 451 (or a variant thereof);
and/or
(ii) a light chain variable region (LCVR) that comprises the light chain complementarity determining region 1 (LCDR1), LCDR2, and LCDR3 of an LCVR comprising the amino acid sequence set forth in SEQ ID NO: 5, 13, 21, 29, 37, 45, 53, 61, 69, 77, 85, 93, 101, 109, 117, 125, 133, 141,437, or 459 (or a variant thereof).
The specification discloses several anti- CACNG1 having distinct HCVRs (Tables 1-2). The specification discloses that a variant of a polypeptide may include a polypeptide such as an immunoglobulin chain which may include the amino acid sequence of the reference polypeptide whose amino acid sequence is specifically set forth herein but for one or more (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10) mutations, e.g., one or more missense mutations (e.g., conservative substitutions), non-sense mutations, deletions, or insertions (paragraph 247).
The state of the prior art is such that it is well established in the art that the formation of an intact antigen-binding site of antibodies routinely requires the association of the complete heavy and light chain variable regions of a given antibody, each of which consists of three CDRs or hypervariable regions, which provide the majority of the contact residues for the binding of the antibody to its target epitope (Paul, Fundamental Immunology, 3rd Edition, 1993, pp. 292-295, under the heading “Fv Structure and Diversity in Three Dimensions”). 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 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 (Paul, page 293, first column, lines 3-8 and line 31 to column 2, line 9 and lines 27-30). 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 as evidenced by Rudikoff et al (Proc. Natl. Acad. Sci. USA, 79(6):1979-1983, March 1982). Rudikoff et al. teach 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.
Colman P. M. (Research in Immunology, 145:33-36, 1994) teaches that even a very conservative substitution may abolish binding or may have very little effect on the binding affinity (see pg. 35, top of left column and pg. 33, right column). While there are some publications, which acknowledge that CDR3 is important, the conformations of other CDRs as well as framework residues influence binding. Pascalis et al (Journal of Immunology, 2002, Vol. 169, pp. 3076-3084) demonstrate that grafting of the CDRs into a human framework was performed by grafting CDR residues and maintaining framework residues that were deemed essential for preserving the structural integrity of the antigen binding site (see page 3079, right col.). Although abbreviated CDR residues were used in the constructs, some residues in all 6 CDRs were used for the constructs (see page 3080, left col.). The fact that not just one CDR is essential for antigen binding or maintaining the conformation of the antigen binding site, is underscored by Casset et al (Biochemical and Biophysical Research Communications, 2003, Vol. 307, pp. 198-205), which constructed a peptide mimetic of an anti-CD4 monoclonal antibody binding site by rational design and the peptide was designed with 27 residues formed by residues from 5 CDRs (see entire document). Casset et al. also states that although CDR H3 is at the center of most if not all antigen interactions, clearly other CDRs play an important role in the recognition process (page 199, left col.) and this is demonstrated in this work by using all CDRs except L2 and additionally using a framework residue located just before the H3 (see page 202, left col.).
It is unlikely that antibodies, which do not contain all of the specific heavy and light chain CDRs of the antibody REGN10717 in their proper order and in the context of framework sequences, which maintain their correct spatial orientation, have the requisite CACNG1 binding function. It is not clear which of the one or more amino acids in the CDRs from REGN10717 may be substituted, deleted or added. Furthermore, there is nothing in the specification which would suggest that mixing and matching the various CDRs from the different anti- CACNG1 antibodies would result in the requisite binding to CACNG1.
The specification does not provide adequate written description of the claimed genus of antibodies that bind CACNG1. The legal standard for sufficiency of a patent's (or a specification's) written description is whether that description "reasonably conveys to the artisan that the inventor had possession at that time of the. . .claimed subject matter", Vas-Cath, Inc. V. Mahurkar, 19 USPQ2d 1111 (Fed. Cir. 1991). In the instant case, the specification does not convey to the artisan that the Applicant had possession at the time of invention the genus of antibodies that bind CACNG1.
The guidelines for the Examination of Patent Applications Under the 35 U.S.C. 112, § 1 "Written Description" Requirement make clear that if a claimed genus does not show actual reduction to practice for a representative number of species, then the Requirement may be alternatively met by reduction to drawings, 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 genus (Federal Register, Vol. 66, No. 4, pages 1099-1111, Fri. January 5, 2001, see especially page 1106 column 3).
The specification does not provide adequate written description of the claimed invention. The legal standard for sufficiency of a patent's (or a specification's) written description is whether that description "reasonably conveys to the artisan that the inventor had possession at that time of the. . .claimed subject matter", Vas-Cath, Inc. V. Mahurkar, 19 USPQ2d 1111 (Fed. Cir. 1991). In the instant case, the specification does not convey to the artisan that the Applicant had possession at the time of invention of the claimed invention, the genus of antibodies that bind CACNG1. The genus of antibodies are claimed by function, the capability of binding to CACNG1. The specification does not disclose which amino acids may be added, subtracted or deleted and maintain binding to CACNG1. In addition, the specification does not disclose that mixing and matching the various CDRs from the different anti- CACNG1 antibodies would result in the requisite binding to CACNG1. The Federal Circuit addressed the application of the written description requirement to DNA-related inventions in University of California v. Eli Lilly and Co., 119 F.3d 1559, 43 USPQ2d 1398 (Fed. Cir. 1997). The court stated that “[a] written description of an invention involving a chemical genus, like a description of a chemical species, requires a precise definition, such as by structure, formula, [or] chemical name, of the claimed subject matter sufficient to distinguish it from other materials.” Id. At 1567, 43 USPQ2d at 1405. The court concluded that “naming a type of material generally known to exist, in the absence of knowledge as to what that material consists of, is not a description of that material.” Id.
The Federal Circuit clarified that a molecule can be adequately described without disclosing its complete structure. See Enzo Biochem, Inc. V. Gen-Probe Inc., 296 F.3d 1316, 63 USPQ2d 1609 (Fed. Cir. 2002). The Enzo court adopted the standard that the written description requirement can be met by “show[ing] 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. “ Id. At 1324, 63 USPQ2d at 1613 (emphasis omitted, bracketed material in original).
However, without a correlation between structure and function, the claim does little more than define the claimed invention by function. That is not sufficient to satisfy the written description requirement. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406 (“definition by function … does not suffice to define the genus because it is only an indication of what the gene does, rather than what it is”).
Thus, the instant specification may provide an adequate written description of the genus of antibodies that bind CACNG1, per Lilly by structurally describing a representative number of antibodies encompassed by the present claims that are capable of binding CACNG1 or by describing structural features common to the members of the genus, which features constitute a substantial portion of the genus.
It is noted that AbbVie v. Janssen Biotech and Centocor Biologics (Fed. Cir. 2014) confirms a strong Post-Ariad Written Description requirement - especially with regard to genus-species claim situations. In the decision, Judge Lourie focuses particularly on the alleged infringing antibodies and notes that: [While] AbbVie patents need not describe the allegedly infringing [compound] in exact terms . . . [t]he patents must at least describe some species representative of antibodies that are structurally similar to [the accused compound]. Because the patent document lacked any such structural description, the court confirmed that the corresponding claims were invalid under 112(a). In discussing the case, Judge Lourie was clear that one problem here is that the invention was described in terms of its function rather than its structure. Lourie writes:
Functionally defined genus claims can be inherently vulnerable to invalidity challenge for lack of written description support, especially in technology fields that are highly unpredictable, where it is difficult to establish a correlation between structure and function for the whole genus or to predict what would be covered by the functionally claimed genus.
The Court has indicated in Amgen Inc vs Sanofi ( 2017-1480, Fed Cir, 2017) that the disclosure of a well characterized antigen is insufficient for an adequate written description of the antibody that binds the antigen. The Court stated that “an adequate written description must contain enough information about the actual makeup of the claim products – a precise definition such as by structure, formula, chemical name, physical properties, or other properties, of species falling within the genus sufficient to distinguish the genus from other material,” which may be present in “function “terminology “when the art has established a correlation between structure and function” (page 17, 1st paragraph). The Court went on to indicate that knowledge of the chemical structure of an antigen does not tell you anything about the structure of the antibody (Id).
In this case, the specification does not sufficiently describe the genus of antibodies that bind CACNG1 and thus does not satisfy either the Lilly nor Enzo standards. The specification only describes one antibody within the claimed genus and the specification does not disclose which of the one or more amino acids may be substituted, added or deleted and maintain binding to CACNG1 or which of the many listed CDRs may be mixed and still maintained binding to CACNG1. Thus, the specification does not appear to describe any species within the genus of antibodies that bind CACNG1. There are insufficient structural features common to all members of the genus of antibodies that bind CACNG1. One of ordinary skill in the art would not be able to identify the broadly claimed genus of antibodies that bind CACNG1.
Thus, the specification does not provide an adequate written description of the genus of antibodies that bind CACNG1 that is required to practice the claimed invention. Applicants have not described the genus of autoantibodies sufficiently to show they had possession of the claimed genus. Since the disclosure fails to provide sufficient relevant identifying characteristics, and because the genus is highly variant, one of skill in the art would reasonably conclude that the disclosure fails to provide a representative number of species to describe the genus as broadly claimed.
An anti- CACNG1 antibody comprising: a VH CDR1 comprising the amino acid sequence of SEQ ID NO: 74; a VH CDR2 comprising the amino acid sequence of SEQ ID NO: 75; a VH CDR3 comprising the amino acid sequence of SEQ ID NO: 76; a VL CDR1 comprising the amino acid sequence of SEQ ID NO: 78; a VL CDR2 comprising the amino acid sequence of SEQ ID NO: 13; and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 14, is free of the art.
Summary
No claims allowed.
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/MARK HALVORSON/Primary Examiner, Art Unit 1646
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