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 .
Application Status
The Response to the Election of Species Requirement filed August 24, 2026 has been entered. Applicant's election without traverse of the anti-BCMA binding moiety comprising the heavy chain CDRs of the VH of SEQ ID NO: 270 and the light chain CDRs of the VL of SEQ ID NO: 551, and the corresponding scFv amino acid sequence of SEQ ID NO: 601, is acknowledged. Applicant has not indicated which claims read on the elected invention.
The claims filed on August 24, 2026 are acknowledged. Claims 88-112 are pending. No claims have been amended, newly added, or canceled. Claims 97-102 and 106 are withdrawn by the Examiner from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking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.
Claims 88-96, 103-105, and 107-112 are under examination herein.
Information Disclosure Statements
Applicant’s duty to disclose information material to the patentability of the claimed invention is noted. In the instant application, the Examiner would like to note that Applicant has submitted information disclosure statement(s) with a total of 2088 references. While the Examiner has made every effort to thoroughly review these references, one could have very well missed a pertinent document.
As noted in MPEP § 2004, “it is desirable to avoid the submission of long lists of documents if it can be avoided”. If a long list is submitted, Applicant has an obligation to call the most pertinent prior art to the attention of the Patent Office in a proper fashion and not “to disclose a pertinent prior art patent reference to the examiner in such a way as to ‘bury’ it or its disclosures in a series of disclosures of less relevant prior art references” (See Penn Yan Boats, Inc. v. Sea Lark Boats, Inc., 359 F. Supp. 948, 175 USPQ 260 (S.D. Fla. 1972), Golden Valley Microwave Food Inc. v. Weaver Popcorn Co., 837 F. Supp. 1444, 24 USPQ2d 1801 (N.D. Ind. 1992)).
Specification
The disclosure is objected to for the following informalities: The brief description for Figure 25 (¶ 0064) contains an incomplete sentence.
Appropriate correction (without introducing new matter) is required.
Claim Rejections - 35 USC § 112(b)
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 88-96, 103-105, and 107-112 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 88 recites an anti-BCMA binding moiety comprising a heavy chain variable region (VH) comprising “the HCDR1, HCDR2, and HCDR3 contained within the VH amino acid sequence set forth in any one of SEQ ID NOS:260-285 and 1582-1600” and a light chain variable region (VL) comprising “the LCDR1, LCDR2, and LCDR3 contained within the VH amino acid sequence set forth in any one of SEQ ID NOS:541-566 and 1677-1695”. However, the claim does not set forth a numbering scheme by which each of the HCDR and LCDR sequences are determined, such as according to Kabat numbering or EU numbering. Accordingly, the intended metes and bounds of the claimed subject matter are indefinite.
Dependent claims 89-96, 103-105, and 107-112 do not remedy this deficiency and are similarly rejected.
This rejection could be obviated if claim 88 were amended to further recite the numbering scheme(s) used to determine the boundaries of the HCDR and LCDR sequences, commensurate in scope with what is disclosed in the specification at the time of filing.
Further regarding claim 108, the claim recites an immune cell comprising “the BCMA-directed CAR of claim 88”. There is insufficient antecedent basis for this limitation in the claim. Claim 88 recites an anti-BCMA binding moiety, but not a BCMA-directed CAR.
Dependent claims 109-112 do not remedy this deficiency and are similarly rejected.
Claim Rejections - 35 USC § 112(a)
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 88-90, 94-95, 103-105, and 107-112 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.
“[T]he purpose of the written description requirement is to ‘ensure that the scope of the right to exclude, as set forth in the claims, does not overreach the scope of the inventor’s contribution to the field of art as described in the patent specification.’” Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1353-54 (Fed. Cir. 2010) (en banc) (quoting Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 920 (Fed. Cir. 2004)). To satisfy the written description requirement, the specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1562-63, 19 USPQ2d 1111 (Fed. Cir. 1991).
MPEP § 2163 states that 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, or it may be satisfied by the 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. “Functional” terminology may be used “when the art has established a correlation between structure and function” but “merely drawing a fence around the outer limits of a purported genus is not an adequate substitute for describing a variety of materials constituting the genus and showing one has invented a genus and not just a species. Ariad Pharmaceuticals Inc. v. Eli Lilly & Co., 598 F3d 1336, 94 USPQ2d 1161, 1171 (Fed Cir. 2010).
For a claim to a genus, a generic statement that defines a genus of substances by only their functional activity does not provide an adequate written description of the genus. Reagents of the University of California v. Eli Lilly, 43 USPQ2d 1398 (CAFC 1997). “[A] sufficient description of a genus . . . requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can ‘visualize or recognize’ the members of the genus.” Ariad, 598 F.3d at 1350 (quoting Eli Lilly, 119 F.3d at 1568-69). A “representative number of species” means that those species that are adequately described are representative of the entire genus. AbbVie Deutschland GMBH v. Janssen Biotech, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014). Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus to provide a "representative number” of species. The “structural features common to the members of the genus” needed for one of skill in the art to ‘visualize or recognize’ the members of the genus takes into account the state of the art at the time of the invention. For example, the Federal Circuit has found that possession of a mouse antibody heavy and light chain variable regions provides a structural "stepping stone" to the corresponding chimeric antibody, but not to human antibodies. Centocor Ortho Biotech Inc. v. Abbott Labs., 97 USPQ2d 1870, 1875 (Fed. Cir. 2011).
Amgen Inc. v. Sanofi, Aventisub LLC, 872 F.3d 1367 (Fed. Cir. 2017) supported previous decisions (Centocor Ortho Biotech, Inc. v. Abbott Labs., 636 F.3d 1341 (Fed. Cir. 2011); AbbVie Deutschland GmbH & Co. v. Janssen Biotech, Inc., 759 F.3d 1285 (Fed. Cir. 2014)) that defining an antibody solely by what it binds does not satisfy the written description requirement, stating that this would allow patentees to “claim antibodies by describing something that is not the invention, i.e., the antigen”. Thus, claiming an antibody by describing the invention by what it does (function) rather than what it is (structure) is invalid. This can be overcome if a relevant number of species with structure/function correlation is known to the art or present in the specification.
The claimed invention. The nature and scope of the claimed invention at issue is an anti-BCMA binding moiety as set forth in claim 88, which comprises a heavy chain variable region (VH) comprising three HCDRs and a light chain variable region (VL) comprising three LCDRs, wherein the three HCDRs are contained within the VH amino acid sequence set forth in “any one of” SEQ ID NOs: 260-285 and 1582-1600 and the LCDRs are contained within the VL amino acid sequence set forth in “any one of” SEQ ID NOs: 541-566 and 1677-1695. This limitation fails to satisfy the written description requirement because the claim language allows for the respective sets of HCDRs and LCDRs to be “mixed and matched” to form any of 1575 (45×35) possible combinations, but not all conceivable combinations of the heavy chain and light chain CDRs set forth in the respective VH and VL domains would be expected to result in a functional antigen binding protein as required by the instant claims except for those combinations specifically enumerated in the disclosure.
It is noted that claims 91-93 and 96, which do recite specific VH/VL pairings having written description support in the disclosure, are not included in this rejection.
State of the prior art. It is well established in the art that the formation of an intact antigen-binding site in an antibody usually requires the association of the complete heavy and light chain variable regions of a given antibody, each of which comprises three CDRs (or hypervariable regions) that provide the majority of the contact residues for the binding of the antibody to its target epitope. See Almagro (Frontiers in Immunology (2018) 8: 1751), “The IgG Molecule” (page 3) and Figure 1. Sela-Culang (Frontiers in Immunology (2013) 4: 302) further teaches, “A major focus in analyzing the structural basis for [antigen] recognition has been in identifying the exact boundaries of the CDRs in a given [antibody]. It is a common practice to identify paratopes through the identification of CDRs” (page 3).
Although the prior art teaches some understanding of the structural basis of antigen-antibody recognition, it is aptly noted that the art is characterized by a high level of unpredictability, since the skilled artisan still cannot accurately and reliably predict the consequences of amino acid substitutions, insertions, and deletions in the antigen-binding domains. Ni (The Protein Journal (2024) 43: 683-696) teaches, “Mutations, even one mutation, introduced in the CDRs through [somatic hypermutation] can change the binding properties and repertoire of antibodies. However, how just one-point mutation can dramatically change the recognition profiles of the antibody is still unclear” (Introduction). Furthermore, while affinity maturation techniques can result in differences in the CDRs of the antibody compared to its parental antibody, those techniques involve trial-and-error testing and the changes that maintain or improve affinity are not predictable a priori (Almagro, pages 3 and 6-7).
Anti-BCMA binding moieties comprising a complete complement of three HCDRs and three LCDRs are well documented in the prior art. Consider, for example, the teachings of Terrett (U.S. Patent No. 11,254,912 and US 2021/0060072 A1; both cited in IDS), Satpayev (US 2021/0388100 A1; cited in IDS), Brentjens (U.S. Patent No. 10,918,665 and US 2018/0118842 A1; both cited in IDS), Morgan (US 2019/0388526 A1; cited in IDS), and Brogdon (US 2019/0153061 A1; cited in IDS).
Scope of species disclosed in original specification. Figures 2-4 enumerate 26 specific scFv constructs of the invention comprising a specific combination of HCDRs from the claimed VH domains having the amino acid sequences of SEQ ID NOs: 260-285, respectively, and LCDRs from the claimed VL domains having the amino acid sequence of SEQ ID NOs: 541-566, respectively. The scFvs comprising the amino acid sequences of SEQ ID NOs: 593-618 and 671-696 (set forth in claim 96) comprise the respective pairings of said VH and VL domains, wherein the VH is N-terminal to the VL in the scFvs comprising SEQ ID NOs: 593-618 and the VL is N-terminal to the VH in the scFvs comprising SEQ ID NOs: 671-696 (e.g., ¶ 0122-0123 of specification).
The disclosure does not provide a similarly clear showing of specific functional pairings between VH domains comprising one of SEQ ID NOs: 1582-1600 and VL domains comprising one of SEQ ID NOs: 1677-1695. However, based on the Sequence Listing of record, there appears to at least be support for selected VH/VL pairings including (1) the VH of SEQ ID NO: 1600 and the VL of SEQ ID NO: 1695, which are comprised in scFv constructs comprising the amino acid sequences of SEQ ID NOs: 1733 and 1847, and (2) the VH of SEQ ID NO: 1586 and the VL of SEQ ID NO: 1681, which are comprised in scFv constructs comprising the amino acid sequences of SEQ ID NOs: 1719, 1776, 1833, and 1871.
MPEP § 2163 states that a “representative number of species” means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. In the absence of a representative number of species, the written description requirement for a claimed genus may be satisfied 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.
As provided above, the state of the art recognizes that the pairing of three heavy chain CDRs with three light chain CDRs in a conventional antibody is unpredictable. Accordingly, while Applicant’s disclosure contains support for selected combinations of an anti-BCMA VH domain having an amino acid sequence of one of SEQ ID NOs: 260-285 or 1582-1600 and an anti-BCMA VL domain having an amino acid sequence of one of SEQ ID NOs: 541-566 or 1677-1695, Applicant does not have written description support for all 1575 conceivable combinations of VH/VL pairs as presently set forth in the instant claims.
Conclusion. For the reasons presented above, one of skill in the art would not know which of the countless other antibodies encompassed by the highly general structural requirements of the claims would also possess the required functional activity. Given the lack of shared structural properties that provide the claimed binding activity, the limited number of species described, and the fact that the species that were described cannot be considered representative of the broad genus, the Applicant did not possess the full genus of anti-BCMA antibodies as broadly claimed at the time the application was filed.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Elizabeth A Shupe whose telephone number is (703) 756-1420. The examiner can normally be reached Monday to Friday, 9:30am - 6:00pm EST.
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/ELIZABETH A SHUPE/Examiner, Art Unit 1643
/JULIE WU/Supervisory Patent Examiner, Art Unit 1643
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