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 .
DETAILED ACTION
1. The Amendment filed January 27, 2026 in response to the Office Action of October 27, 2025 is acknowledged and has been entered. Claims 1-12 have been cancelled. New claims 13-32 have been added.
2. Claims 13-32 are currently being examined.
New Grounds of Rejection
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.
3. Claim 16 is 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 16 recites the limitation " wherein the one or more amino acid substitutions" in lines 2-4. There is insufficient antecedent basis for this limitation in the claim because claim 13 from which claim 16 depends does not recite one or more amino acid substitutions.
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.
4. Claims 13-16 and 20-32 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.
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 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. A “representative number of species” means that the species which are adequately described are representative of the entire genus. See, e.g., AbbVie Deutschland GMBH v. Janssen Biotech, 759 F.3d 1285, 111 USPQ2d 1780 (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. “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).
Scope of the claimed genus
The claims are drawn broadly drawn to an isolated or purified antibody (Ab), or antigen (Ag) binding fragment thereof, or monomeric or dimeric antigen binding protein (ABP), capable of specifically binding a human B-cell maturation antigen (BCMA) polypeptide (also called tumor necrosis factor receptor superfamily member 17 (TNFRSF17)), wherein the isolated or purified Ab, or Ag binding fragment thereof, or monomeric or dimeric ABP comprises the VH and VL of SEQ ID NOs: 1-6, the CDR regions thereof, and variants thereof comprising one or more of the disclosed VH and VL and variants thereof. Thus the claims are broadly drawn to a large genus of an isolated or purified Ab, or Ag binding fragment thereof, or monomeric or dimeric ABP, capable of specifically binding a human BCMA.
State of the Relevant Art
As was well-known in the antibody art, antibodies as a class share an overall structure generally comprising two heavy chain polypeptides that each comprises a heavy chain variable region (VH) and a heavy chain constant region made up of several domain (CH1, hinge, CH2, CH3, and for some antibodies, a CH4). Each of the heavy chains pairs with a light chain polypeptide that comprises a light chain variable region (VL) and a constant region. But while this overall structure is shared amongst antibodies from a wide variety of sources (human, rat, mouse, rabbit), the structure each antibody uses to bind its particular epitope on an antigen is structurally distinct and is formed by a recombination event that results in high variability at the amino acid sequence level. By the time the invention was made, it is well established in the art that the formation of an intact antigen-binding site in an antibody usually required the association of the complete heavy and light chain variable regions of a given antibody, each of which consists of three “complementarity determining regions” (“CDRs”) which provide the majority of the contact residues for the binding of the antibody to its target epitope. See Almagro & Fransson, Frontiers in Bioscience 2008; 13:1619-33 (of record, see Section 3) “Antibody Structure and the Antigen Binding Site” and Figure 1). Chimeric antibodies comprise the heavy and light chain variable regions of a rodent antibody linked to human constant regions and preserve the entirety of the VH and VL of the parent antibody. Id. at 1619-20. Humanized antibodies comprise only the CDRs, or in some cases an abbreviated subset of residues within the CDRs, of a parental rodent antibody in the context of human framework sequences. Id. at Section 4. All of the CDRs of the heavy and light chain, in their proper order of CDR1, then 2, then 3, and in the context of framework sequences which maintain their required conformation are generally required to produce a humanized antibody in which the heavy and light chains associate to form an antigen-binding region that binds the same antigen as the parental rodent antibody. Id. at Section 4. Almagro provides a detailed discussion regarding various methods of humanization, including rationale design approaches and empirical approaches based on random screening. Almagro, Sections 4 and 5.
Overall, at the time the invention was made, the level of skill for preparing antibodies and then selecting those antibodies with desired functional properties was high. However, even if a selection procedure was, at the time of the invention, sufficient to enable the skilled artisan to identify antibodies with the recited functional properties, the written description provision of 35 U.S.C § 112 is severable from its enablement provision. Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336 (Fed. Cir. 2010); see also Centocor Ortho Biotech Inc. v. Abbott Labs., 97 USPQ2d 1870, 1876 (Fed. Cir. 2011) (“The fact that a fully-human antibody could be made does not suffice to show that the inventors of the '775 patent possessed such an antibody.”) Absent the conserved structure provided by all six CDRs of a parental antibody in the context of appropriate VH and VL framework sequences, the skilled artisan generally would not be able to visualize or otherwise predict, a priori, what an antibody with a particular set of functional properties would look like structurally.
Summary of Species disclosed in the original specification
The specification teaches the monoclonal antibodies 9H5, 10A2, and 5C1 which comprise the VH and VL of SEQ ID NOs: 1-6 and bind BCMA. See BCMA antibody clone development- pp. 34-42.
Are the disclosed species representative of the claimed genus?
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.
The specification discloses the reduction to practice of monoclonal antibodies 9H5, 10A2, and 5C1 which comprise the VH and VL of SEQ ID NOs: 1-6 and bind human BCMA. The specification does not actually produce any other antibodies that bind BCMA or make any other forms of the monoclonal antibodies 9H5, 10A2, and 5C1, such as a single domain antibody or other antibodies or ABP that contain a plurality of CDR fragments. Antibodies produced by different methods, such as in different species or in phage, would have been generally expected to be highly structurally diverse, particularly in the CDR sequences. Thus, while applicant has described three species, the genus of antibodies very large and there is only three described species for the genus. The described species therefore cannot be considered representative of the genus an isolated or purified Ab, or Ag binding fragment thereof, or monomeric or dimeric ABP, capable of specifically binding a human BCMA. E.g., AbbVie Deutschland GMBH v. Janssen Biotech, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014).
Identifying characteristics and structure/function correlation
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. To meet this requirement in the instant case, the specification must describe structural features that convey the claimed binding activity, a prerequisite for utility in the recited methods of treating.
As noted above, the art generally accepted that the combination of the CDRs within the VH and VL pair of an antibody were essential for binding specificity. But the specification does not describe what residues within the CDRs confer the binding activity claimed. Accordingly, the skilled artisan would not be able to discern a structure/function correlation for antibodies other than those comprising either all six CDRs (in the context of VH and VL regions) of one parental antibody, or the VH and VL of one parental antibody.
For all of the reasons presented above, one of skill in the art would not know which of the countless other antibodies encompassed by the independent claims that meet the highly general structural requirements of the claims would also be able to specifically bind to human BCMA. Neither the specification nor the dependent claims provide sufficient additional structure or a structure/function correlation to provide an adequate written description of the genera claimed. Therefore, the skilled artisan would not reasonably conclude that the inventors, at the time the application was filed, had full possession of an isolated or purified Ab, or Ag binding fragment thereof, or monomeric or dimeric ABP, capable of specifically binding a human BCMA as broadly claimed. 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, Applicant was not in possession of the invention as claimed.
Response to Arguments
5. Applicant argues that claim 1 argues that claim 1 has been cancelled rendering the rejections moot.
Applicant’s arguments have been considered, but have not been found persuasive with respect to claims 13-16 and 20-32. The claims still encompass variants of VH and VL of SEQ ID NOs: 1-6 or the CDR regions thereof comprising one or more of the disclosed VH and VL and variants thereof. Thus the claims are still broadly drawn to a large genus of an isolated or purified Ab, or Ag binding fragment thereof, or monomeric or dimeric ABP, capable of specifically binding a human BCMA. However, the specification only discloses monoclonal antibodies 9H5, 10A2, and 5C1 which comprise the VH and VL of SEQ ID NOs: 1-6 that bind human BCMA. The specification does not actually produce any other antibodies or ABP that bind human BCMA or make any other forms of the monoclonal antibodies 9H5, 10A2, and 5C1, e.g., a single domain antibody or other antibodies or ABP that contain a plurality of CDR fragments, that bind human BCMA. Thus, for the reasons forth above the specification as filed does not adequately describe the broadly claimed Ab, or Ag binding fragment thereof, or monomeric or dimeric ABP, capable of specifically binding a human BCMA.
6. Claim(s) 25-30 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by US 2020/0392236 A1 (Sather et al. Dec. 17, 2020,IDS), “Sather”.
It is noted that claim 25 recites “(a) contacting the cell, tissue or organ or portion of any of the foregoing with a first Ab, or Ag binding fragment thereof, or monomeric or dimeric ABP of claim 13” lines 4-5. Thus, the claim is interpreted to encompass the alternative of contacting with any first Ab or any Ag binding fragment thereof, which are not limited to the Ab or Ag binding fragment thereof of claim 13.
Also the first alternative steps of claims 26 (lines 1-3) and 28 (lines 1-2) are not limited to contacting with the Ab or Ag binding fragment thereof of claim 13 or ABP of claim 13 as the second Ab or Ag binding fragment.
Sather teaches antibodies to human BCMA. See abstract and ¶¶ 0006 and 0048.
Sather teaches diagnosing cancer with the anti-BCMA antibodies using ELISA assays, which use two antibodies, by detecting BCMA in cells or tissues. See ¶¶ 0204, 0395, 0409-0411, and 0523-0531.
Sather teaches a subject may be screened for the presence of a disease or disorder associated with elevated BCMA expression, such as a BCMA-expressing cancer or tumor like lymphoma (e.g. non-Hodgkin's lymphoma (NHL), Hodgkin's lymphoma) or leukemia. Sather teaches a subject who tests positive for a BCMA-associated disease or disorder may be selected for treatment by the present methods, and may be administered a therapeutically effective amount of a BCMA-binding molecule (e.g., anti-BCMA antibody or antigen-binding fragment thereof), recombinant receptor (e.g., CAR) comprising a BCMA-binding molecule, cells containing a recombinant receptor or a pharmaceutical composition thereof as described herein. See ¶¶ 0409-0412.
Sather teaches treating the cancer, like lymphoma (e.g. non-Hodgkin's lymphoma (NHL), Hodgkin's lymphoma) or leukemia, with the anti-BCMA antibodies. See ¶¶ 0074-0076, 0406, 0409-0411 and 0415 and claims 76, 77 and 85-88.
Conclusion
7. All other objections and rejections recited in the Office Action of October 27, 2025 are withdrawn in view of Applicant’s amendments.
8. Claims 13-16 and 20-32 are rejected. Claims 17-19 are 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.
9. No claims allowed.
10. Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the date of this final action.
11. Any inquiry concerning this communication or earlier communications from the examiner should be directed to PETER J REDDIG whose telephone number is (571)272-9031. The examiner can normally be reached on M-F 8:30-5:30 Eastern Time
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/Peter J Reddig/
Primary Examiner, Art Unit 1642
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