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 with traverse of Group I (claim 37) and the below-listed species of antibody in the reply filed on 10/28/2025 is acknowledged.
Elected Species:
Anti-BCMA antibody comprising: (i) HCDRs1-3 set forth in SEQ ID NOs: 26, 78, and 136, respectively; (ii) a VH comprising SEQ ID NO: 251; and (iii) a heavy chain comprising SEQ ID NO: 319.
It is noted that new claims 38-40, 43, and 44 all depend from elected claim 37. As such, new claims 38-40 and 43-44 are considered to belong to elected Group I. New claims 41-42 correspond to non-elected Group II, and new claims 45-48 correspond to non-elected Group III.
With regard to Applicant’s election with traverse, Applicant argues the following:
All of the pending claims relate to the anti-BCMA antibody set forth in the Group I claims (i.e., claims 37-40 and 43-44), which constitute a single general inventive concept. Pursuant to PCT Rule 13.1 (governing here since the instant application is a US national application), the pending claims share unity of invention.
The elected species of the anti-BCMA antibody and structurally related non-elected species encompassed by the instant claims. As noted above, the elected anti-BCMA antibody species, comprising the HCDRl, HCDR2, and HCDR3 sequences of SEQ ID NOs: 26, 78, and 136, respectively, corresponds to antibody clone PR001046 (see, for example, Table 7-8 of the specification as-filed). Table 7-8 further lists 16 variants of clone PR001046, designated as clones PR004559-PR004574, and provides their HCDRl, HCDR2, and HCDR3 sequences, and the corresponding VH and heavy chain sequences. As disclosed in Example 7.6, the variant clones PR004559-PR004574 are obtained through introducing point mutations in the CDR regions of clone PR001046. As such, the combinations of CDR sequences corresponding to the elected antibody (with heavy chain CDRs of PR001046) and the non-elected species (with heavy chain CDRs of PR004559-PR004574) exhibit either identical CDR sequences or CDR sequences that differ by at most two amino acid residues relative to the parent antibody clone PR001046.
Applicant’s arguments have been fully considered, but are deemed not persuasive.
It is acknowledged that, as amended, the technical feature shared among the previously identified groups of invention is, generically, an anti-BCMA antibody comprising a VH that further comprises HCDRs 1-3. It is specifically noted that the now claimed HCDR1-3 combinations recited in independent claim 37 all differ from each other, as indicated by Applicant wherein the different CDRs may comprise up to two point mutations each. As such, the CDR sequences themselves are not the technical feature, but rather a generic anti-BCMA antibody that comprises a VH that further comprises HCDRs 1-3. In view of the claim amendment, it is noted that the newly identified technical feature does not make a contribution over the prior art in view of US 2016/0046724 A1 (herein after referred to as “Brogdon”).
Brogdon discloses compositions and methods for treating diseases associated with BCMA expression and chimeric antigen receptors (CARs) specific to BCMA that comprise a BCMA binding domain (Abstract). It is further noted that the antigen-binding domains of the invention may be a human or humanized antibody or antibody fragment that specifically binds to BCMA (Paragraph 0031); “antibody fragment” refers to at least one portion of an intact antibody, or recombinant variants thereof, and refers to the antigen binding domain, e.g., an antigenic determining variable region of an intact antibody, that is sufficient to confer recognition and specific binding of the antibody fragment to a target, such as an antigen, wherein examples of antibody fragments include, but are not limited to, Fab, Fab′, F(ab′)2, and Fv fragments, scFv antibody fragments, linear antibodies, single domain antibodies such as sdAb (either VL or VH), camelid VHH domains, and multi-specific molecules formed from antibody fragments such as a bivalent fragment comprising two or more, e.g., two, Fab fragments linked by a disulfide bridge at the hinge region, or two or more, e.g., two isolated CDR or other epitope binding fragments of an antibody linked further wherein an antibody fragment can also be incorporated into single domain antibodies, maxibodies, minibodies, nanobodies, intrabodies, diabodies, triabodies, tetrabodies, v-NAR and bis-scFv (Paragraph 0176). In certain embodiments, the BCMA CAR molecules or the anti-BCMA binding domain of the invention include one, two, or three CDRs from the heavy chain variable region as provided in Table 22 (Paragraph 0086). Thus, Brogdon reads on antigen binding domains which may be antibodies or antibody fragments, including single domain antibodies only comprising a VH/HCDRs 1-3, wherein said antibody or antibody fragment is specific for BCMA. As such, the technical feature of an anti-BCMA antibody that comprises a VH that further comprises HCDRs 1-3 is not a special technical feature as it does not make a contribution over the prior art.
In view of the above, the Restriction/Election requirement is maintained and is made FINAL.
Claim Status
Claims 1-36 have been cancelled; claim 37 has been amended; and, claims 38-48 have been newly added, as requested in the amendment filed on 10/28/2025. Following the amendment, claims 37-48 are pending in the instant application.
Claims 41-42, and 45-48 stand as withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to nonelected inventions in the Response filed 10/28/2025, there being no allowable generic or linking claim.
Claims 37-40 and 43-44 are under examination in the instant office action.
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.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55. However, it is noted that the claim to foreign priority has not been perfected as no English translation of the foreign priority document has been provided.
Claims 37-40 have an effective filing date of June 29, 2021 corresponding to PCT/CN2021/103044, as the claim to foreign priority has not been perfected.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 03/21/2024, 06/26/2024, and 11/12/2024 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements is being considered by the examiner.
The information disclosure statement filed 03/16/2023 fails to comply with 37 CFR 1.98(a)(2), which requires a legible copy of each cited foreign patent document; each non-patent literature publication or that portion which caused it to be listed; and all other information or that portion which caused it to be listed. It has been placed in the application file, but the information referred to therein struck through, listed below, has not been considered.
ZHAO et al., PD-L1: CD80 Cis-Heterodimer Triggers the Co-stimulatory Receptor CD28 While Repressing the Inhibitory PD-1 and CTLA-4 Pathways. Immunity. 2019 Dec 17;51(6):1059-1073.e9. Epub 2019 Nov 19.
Drawings
The drawings are objected to because Figures 48 and 65 comprise illegible components/text/labels. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Interpretation
It is noted that claim 37 recites the following language: “HCDR1, HCDR2 and HCDR3 with amino acid sequences as set forth in…”. It is noted that this claim language as pertains to the recited CDR sequences is being interpreted as open sequence claim language, wherein either the full-length sequences or fragments thereof (e.g., an amino acid sequence comprised therein that is at least two consecutive amino acids in length) satisfy the sequence limitations.
It is noted that claims 38-39 recite the following the claim language with respect to VH and heavy chain sequences, respectively: “comprises the amino acid sequence as set forth in any one of…”. It is noted that this claim language as pertains to the recited VH and heavy chain sequences (claim 38 and 39, respectively) is being interpreted as closed sequence claim language, wherein the full-length sequences are required to satisfy the sequence limitations.
Art-Free Subject Matter
It is noted that the sequences of the instantly elected species of anti-BCMA antibody comprising: (i) HCDRs1-3 set forth in SEQ ID NOs: 26, 78, and 136, respectively; (ii) a VH comprising SEQ ID NO: 251; and (iii) a heavy chain comprising SEQ ID NO: 319 has been thoroughly searched. It is specifically noted, that there are no 100% matches to the above-listed sequences disclosed in the prior art. However, as detailed below, it is noted that instant claims 37-40 suffer from deficiencies under 35 U.S.C. 112, 35 U.S.C. 103, and/or nonstatutory double patenting.
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 37, 40, 43, and 44 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a WRITTEN DESCRIPTION rejection.
The claims are drawn to an anti-BCMA antibody, wherein the anti-BCMA antibody comprises a heavy chain variable region (VH); wherein: the VH comprises HCDR1, HCDR2 and HCDR3 with amino acid sequences as set forth in SEQ ID NOs: 26, 78 and 136, respectively.
Thus, the claims identify the antibody by the function of binding BCMA, and a partial sequence structure that comprises an HCDR1, HCDR2, and HCDR3 with any amino acid sequence as few as two consecutive amino acids as set forth in SEQ ID NOs: 26, 78, and 136, respectively. Thus, the claims encompass a vast genus of antibody variants comprising variable HCDR1, HCDR2, and HCDR3 sequences and required to bind BCMA.
The instant specification discloses four structurally distinct human anti-BCMA HCab antibodies (see Table 7-7).
PNG
media_image1.png
296
698
media_image1.png
Greyscale
The instant specification discloses 16 highly homologous anti-BCMA heavy chain antibody (HCab) variants of parental PR001046 antibody with overlapping HCDR1, HCDR2, and HCDR3 sequences, wherein parental antibody PR001046 comprises instant SEQ ID NOs: 26, 78, and 136, HCDR1, HCDR2, and HCDR3 sequences (see Table 7-8).
PNG
media_image2.png
654
742
media_image2.png
Greyscale
Thus, the instant specification discloses making four structurally distinct HCab antibodies and describes the complete HCDR1, HCDR2, and HCDR3 sequences for PR001046 antibody and its 16 highly homologous HCab variants, that all function to bind BCMA. The specification fails to disclose any other HCDR1, HCDR2, and HCDR3 sequence variants having as few as two consecutive amino acids found in SEQ ID NOs: 26, 78, and 136 that possess the function of binding to BCMA.
To provide adequate written description and evidence of possession of the claimed antibody genus, the instant specification can structurally describe representative antibody variants that function to bind BCMA, or describe structural features common to the members of the genus, which features constitute a substantial portion of the genus. Alternatively, the specification can show that the claimed invention is complete by disclosure of sufficiently detailed, relevant identifying characteristics, functional characteristics when coupled with a known or disclosed correlation between function and structure, or some combination of such characteristics (see University of California v. Eli Lilly and Co., 119 F.3d 1559, 43 USPQ2d 1398 (Fed. Cir. 1997) and Enzo Biochem, Inc. V. Gen-Probe Inc.).
In this case, the only factor present in the claims is a recitation of the antibody function, “anti-BCMA”, and partial sequence structure as stated above. The instant specification fails to describe structural features common to the members of the antibody genus, which features constitute a substantial portion of the genus because the instant specification fails to disclose representative antibody variant sequences that function as claimed. A definition by function does not suffice to define the genus because it is only an indication of what the antibody does, rather than what it is. Other than for the antibodies disclosed in Tables 7-7 and 7-8, the specification fails to provide the HCDR1, HCDR2, and HCDR3 structural features coupled to the claimed functional characteristics. The instant specification fails to describe a representative number of antibody sequence variants for the genus of antibodies that function as claimed. Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the claimed genus required to make the claimed antibodies.
The claims broadly encompass any sequence variant having as few as two amino acids from HCDR1, HCDR2, and HCDR3 SEQ ID NOs: 26, 78, and 136 that functions to bind BCMA. Applicants have not established any reasonable structure-function correlation with regards to the sequences in the CDRs that can be altered and still maintain BCMA binding function Given the well-known high level of polymorphism of antibody CDR sequences and structure, the skilled artisan would not have been in possession of the vast repertoire of antibodies encompassed by the claimed invention. One could not reasonably or predictably extrapolate the structure of a single parental PR001046 antibody comprising SEQ ID NOs:26, 78, and 136 to the structure of any variants required to bind BCMA as broadly claimed. Therefore, one could not readily envision members of the broadly claimed genus.
Although Applicants may argue that it is possible to screen for antibodies that bind BCMA and function as claimed, the court found in (Rochester v. Searle, 358 F.3d 916, Fed Cir., 2004) that screening assays are not sufficient to provide adequate written description for an invention because they are merely a wish or plan for obtaining the claimed chemical invention. “As we held in Lilly, “[a]n adequate written description of a DNA … ‘requires a precise definition, such as by structure, formula, chemical name, or physical properties,’ not a mere wish or plan for obtaining the claimed chemical invention.” 119 F.3d at 1566 (quoting Fiers, 984 F.2d at 1171). For reasons stated above, that requirement applies just as well to non-DNA (or RNA) chemical inventions.” Knowledge of screening methods provides no information about the structure of any future antibodies yet to be discovered that may function as claimed. The BCMA antigen provides no information about the structure of an antibody that binds to it.
Given the lack of representative examples to support the full scope of the claimed variant antibodies, and lack of reasonable structure-function correlation with regards to the unknown variable sequences in the CDRs that provide BCMA-binding function, the present claims lack adequate written description. Thus, the specification does not provide an adequate written description of antibody variants that bind BCMA and comprise as few as two defined consecutive amino acids in each CDR from SEQ ID NOs: 26, 78, and 136 that is required to practice the claimed invention.
Examiner Suggestion: Examiner suggests amending claim 37 to recite: An anti-BCMA antibody, wherein the anti-BCMA antibody comprises a heavy chain variable region (VH); wherein:
the VH comprises HCDR1, HCDR2 and HCDR3 comprising the amino acid sequences as set forth in SEQ ID NOs: 26, 78 and 136, respectively.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 37, 40, and 43 are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by US 2016/0046724 A1 (herein after referred to as "Brogdon").
With regard to claims 37 and 40, Brogdon discloses compositions and methods for treating diseases associated with BCMA expression and chimeric antigen receptors (CARs) specific to BCMA that comprise a BCMA binding domain (Abstract). It is further noted that the antigen-binding domains of the invention may be a human or humanized antibody or antibody fragment that specifically binds to BCMA (Paragraph 0031); “antibody fragment” refers to at least one portion of an intact antibody, or recombinant variants thereof, and refers to the antigen binding domain, e.g., an antigenic determining variable region of an intact antibody, that is sufficient to confer recognition and specific binding of the antibody fragment to a target, such as an antigen, wherein examples of antibody fragments include, but are not limited to, Fab, Fab′, F(ab′)2, and Fv fragments, scFv antibody fragments, linear antibodies, single domain antibodies such as sdAb (either VL or VH), camelid VHH domains, and multi-specific molecules formed from antibody fragments such as a bivalent fragment comprising two or more, e.g., two, Fab fragments linked by a disulfide bridge at the hinge region, or two or more, e.g., two isolated CDR or other epitope binding fragments of an antibody linked further wherein an antibody fragment can also be incorporated into single domain antibodies, maxibodies, minibodies, nanobodies, intrabodies, diabodies, triabodies, tetrabodies, v-NAR and bis-scFv (Paragraph 0176). In certain embodiments, the BCMA CAR molecules or the anti-BCMA binding domain of the invention include one, two, or three CDRs from the heavy chain variable region as provided in Table 22 (Paragraph 0086). It is specifically noted that the antibody designated as C9178-G4 from Table 22 comprises: (i) HCDR1 of sequence GFTFSSY; (ii) HCDR2 of sequence SGSGGS; and (iii) HCDR3 of sequence MGWSSGYLCAFDI; the bolded portions of the sequences correspond to sequence fragments comprised within instantly claimed SEQ ID NOs: 26, 78, and 136, respectively. Thus, Brogdon discloses CARs which comprise antigen binding domains, which may be an antibody or antibody fragment, wherein antibody fragments include single domain antibodies only comprising a VH/HCDRs1-3 (i.e., VHH antibody), wherein said antibody or antibody fragment is specific for BCMA and may comprise fragments of the instantly claimed HCDRs. Thus, Brogdon anticipates instant claims 37 and 40.
With regard to claim 43, Brogdon discloses pharmaceutical compositions of the invention which may comprise a CAR-expressing cell, e.g., a plurality of CAR-expressing cells, as described by the invention, in combination with one or more pharmaceutically or physiologically acceptable carriers, diluents or excipients (Paragraph 0917). The CARs of the CAR-expressing cells may comprise the antibodies or antibody fragments thereof that are specific to BCMA as detailed with regard to instant claim 37. Thus, Brogdon anticipates instant claim 43.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim 44 is rejected under 35 U.S.C. 103 as being unpatentable over US 2016/0046724 A1 (herein after referred to as "Brogdon").
Brogdon discloses compositions and methods for treating diseases associated with BCMA expression and chimeric antigen receptors (CARs) specific to BCMA that comprise a BCMA binding domain (Abstract). It is further noted that the antigen-binding domains of the invention may be a human or humanized antibody or antibody fragment that specifically binds to BCMA (Paragraph 0031); “antibody fragment” refers to at least one portion of an intact antibody, or recombinant variants thereof, and refers to the antigen binding domain, e.g., an antigenic determining variable region of an intact antibody, that is sufficient to confer recognition and specific binding of the antibody fragment to a target, such as an antigen, wherein examples of antibody fragments include, but are not limited to, Fab, Fab′, F(ab′)2, and Fv fragments, scFv antibody fragments, linear antibodies, single domain antibodies such as sdAb (either VL or VH), camelid VHH domains, and multi-specific molecules formed from antibody fragments such as a bivalent fragment comprising two or more, e.g., two, Fab fragments linked by a disulfide bridge at the hinge region, or two or more, e.g., two isolated CDR or other epitope binding fragments of an antibody linked further wherein an antibody fragment can also be incorporated into single domain antibodies, maxibodies, minibodies, nanobodies, intrabodies, diabodies, triabodies, tetrabodies, v-NAR and bis-scFv (Paragraph 0176). In certain embodiments, the BCMA CAR molecules or the anti-BCMA binding domain of the invention include one, two, or three CDRs from the heavy chain variable region as provided in Table 22 (Paragraph 0086). It is specifically noted that the antibody designated as C9178-G4 from Table 22 comprises: (i) HCDR1 of sequence GFTFSSY; (ii) HCDR2 of sequence SGSGGS; and (iii) HCDR3 of sequence MGWSSGYLCAFDI; the bolded portions of the sequences correspond to sequence fragments comprised within instantly claimed SEQ ID NOs: 26, 78, and 136, respectively. Thus, Brogdon discloses CARs which comprise antigen binding domains, which may be an antibody or antibody fragment, wherein antibody fragments include single domain antibodies only comprising a VH/HCDRs1-3 (i.e., VHH antibody), wherein said antibody or antibody fragment is specific for BCMA and may comprise fragments of the instantly claimed HCDRs. Brogdon further discloses, in one embodiment, the cells expressing a CAR molecule, e.g., a CAR molecule described by the invention, may be administered in combination with an agent that treats the disease associated with BCMA, wherein exemplary diseases to be treated include cancer (i.e., a CAR molecule of the invention may be administered in combination with an agent that treats cancer) (Paragraphs 0073-0076). Brogdon specifically discloses methods for preventing relapse of cancer associated with BCMA-expressing cells, the methods comprising administering to a subject in need thereof an anti-BCMA CAR-expressing cell (e.g., BCMA CART cell or BCMA CAR-expressing NK cell) of the invention that binds to the BCMA-expressing cell wherein, in one aspect, the methods comprise administering to the subject in need thereof an effective amount of an anti-BCMA CAR-expressing cell (e.g., BCMA CAR-T cell or BCMA CAR-expressing NK cell) of the invention that binds to the BCMA-expressing cell in combination with an effective amount of another therapy (Paragraph 0699). It is noted that the term "combination" refers to either a fixed combination in one dosage unit form, or a combined administration where a compound of the present invention and a combination partner (e.g. another drug, also referred to as "therapeutic agent" or "co-agent") may be administered independently at the same time or separately within time intervals, especially where these time intervals allow that the combination partners show a cooperative, e.g. synergistic effect; the single components may be packaged in a kit or separately (Paragraph 0189; emphasis added). It is noted that while Brogdon does not explicitly mention an embodiment wherein the CAR molecule and another therapy are provided in a first and second kit, Brogdon does suggest that single components may be packaged in a kit or separately; thus, one of ordinary skill in the art would recognize that the individual components could be provided in separate kits for the treatment of cancer.
Thus, it would have been obvious to one of ordinary skill in the art that the BCMA targeting CAR molecule and another therapy to be used in combination, disclosed by Brogdon, could be provided in a first and second kit, respectively, because Brogdon suggests single components may be packaged in a kit or separately, and one of ordinary skill in the art would recognize that the individual components could be provided in separate kits for the treatment of cancer because combining prior art elements according to known methods would be expected to yield predictable results; one kit providing two active agents, which may be administered separately as suggested by Brogdon, would serve the same purpose as a first and second kit used to provide the same combination of active ingredients useful for the same purpose.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 37-40 and 43 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 14, and 28 of copending Application No. 17/764,308 (herein after referred to as "first reference application"). Although the claims at issue are not identical, they are not patentably distinct from each other.
Claims 1-2 of the first reference application disclose a monoclonal antibody or antigen binding fragment thereof targeting BCMA and comprising a heavy chain variable region wherein: (i) the heavy chain variable region comprises HCDRs1-3 comprising the amino acid sequences of SEQ ID NOs: 22, 33, and 42 and (ii) the heavy chain variable region comprises the amino acid sequence of SEQ ID NO: 59. It is noted that first reference application SEQ ID NOs: 22, 33, 42, and 59 are 100% matches to instant SEQ ID NOs: 26, 78, 136, and 251, respectively. Claim 14 of the first reference application discloses a pharmaceutical composition comprising the monoclonal antibody or antigen binding fragments thereof targeting BCMA of claim 1, and a pharmaceutically acceptable carrier. First reference application claim 28 further discloses that the monoclonal antibody or antigen binding fragments thereof of targeting BCMA of claim 2 comprises a heavy chain having an amino acid sequence of SEQ ID NO: 1. It is specifically noted that first reference application SEQ ID NO: 1 is a 100% match for instant SEQ ID NO: 319. Thus, the first reference application reads on the anti-BCMA antibody of instant claims 37-40 and the pharmaceutical composition of instant claim 43.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 44 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 13, 15, and 28 of copending Application No. 17/764,308 (herein after referred to as "first reference application") in view of US 2016/0046724 A1 (herein after referred to as "Brogdon").
The disclosure of claims 1-2, 14, and 28 of the first reference application are detailed above. Additionally, it is noted that first reference application claim 15 further discloses a method of treating cancer comprising administering an effective amount of the monoclonal antibody or antigen-binding fragments thereof targeting BCMA of claim 1 to a subject. However, it is noted that the first reference application does not teach/suggest kits, including a first and second kit comprising an anti-BCMA antibody and additional antibody or pharmaceutical composition for treating cancer, respectively. This deficiency is remedied by Brogdon.
Brogdon discloses compositions and methods for treating diseases associated with BCMA expression and chimeric antigen receptors (CARs) specific to BCMA that comprise a BCMA binding domain (Abstract). It is further noted that the antigen-binding domains of the invention may be a human or humanized antibody or antibody fragment that specifically binds to BCMA (Paragraph 0031); “antibody fragment” refers to at least one portion of an intact antibody, or recombinant variants thereof, and refers to the antigen binding domain, e.g., an antigenic determining variable region of an intact antibody, that is sufficient to confer recognition and specific binding of the antibody fragment to a target, such as an antigen, wherein examples of antibody fragments include, but are not limited to, Fab, Fab′, F(ab′)2, and Fv fragments, scFv antibody fragments, linear antibodies, single domain antibodies such as sdAb (either VL or VH), camelid VHH domains, and multi-specific molecules formed from antibody fragments such as a bivalent fragment comprising two or more, e.g., two, Fab fragments linked by a disulfide bridge at the hinge region, or two or more, e.g., two isolated CDR or other epitope binding fragments of an antibody linked further wherein an antibody fragment can also be incorporated into single domain antibodies, maxibodies, minibodies, nanobodies, intrabodies, diabodies, triabodies, tetrabodies, v-NAR and bis-scFv (Paragraph 0176). In certain embodiments, the BCMA CAR molecules or the anti-BCMA binding domain of the invention include one, two, or three CDRs from the heavy chain variable region as provided in Table 22 (Paragraph 0086). It is specifically noted that the antibody designated as C9178-G4 from Table 22 comprises: (i) HCDR1 of sequence GFTFSSY; (ii) HCDR2 of sequence SGSGGS; and (iii) HCDR3 of sequence MGWSSGYLCAFDI; the bolded portions of the sequences correspond to sequence fragments comprised within instantly claimed SEQ ID NOs: 26, 78, and 136, respectively. Thus, Brogdon discloses CARs which comprise antigen binding domains, which may be an antibody or antibody fragment, wherein antibody fragments include single domain antibodies only comprising a VH/HCDRs1-3 (i.e., VHH antibody), wherein said antibody or antibody fragment is specific for BCMA and may comprise fragments of the instantly claimed HCDRs. Brogdon further discloses, in one embodiment, the cells expressing a CAR molecule, e.g., a CAR molecule described by the invention, may be administered in combination with an agent that treats the disease associated with BCMA, wherein exemplary diseases to be treated include cancer (i.e., a CAR molecule of the invention may be administered in combination with an agent that treats cancer) (Paragraphs 0073-0076). Brogdon specifically discloses methods for preventing relapse of cancer associated with BCMA-expressing cells, the methods comprising administering to a subject in need thereof an anti-BCMA CAR-expressing cell (e.g., BCMA CART cell or BCMA CAR-expressing NK cell) of the invention that binds to the BCMA-expressing cell wherein, in one aspect, the methods comprise administering to the subject in need thereof an effective amount of an anti-BCMA CAR-expressing cell (e.g., BCMA CAR-T cell or BCMA CAR-expressing NK cell) of the invention that binds to the BCMA-expressing cell in combination with an effective amount of another therapy (Paragraph 0699). It is noted that the term "combination" refers to either a fixed combination in one dosage unit form, or a combined administration where a compound of the present invention and a combination partner (e.g. another drug, also referred to as "therapeutic agent" or "co-agent") may be administered independently at the same time or separately within time intervals, especially where these time intervals allow that the combination partners show a cooperative, e.g. synergistic effect; the single components may be packaged in a kit or separately (Paragraph 0189; emphasis added). It is noted that while Brogdon does not explicitly mention an embodiment wherein the CAR molecule and another therapy are provided in a first and second kit, Brogdon does suggest that single components may be packaged in a kit or separately; thus, one of ordinary skill in the art would recognize that the individual components could be provided in separate kits for the treatment of cancer.
The first reference application and Brogdon are considered to be analogous to the present invention as they are in the same field of anti-BCMA antibodies/antigen binding domains and compositions thereof. Thus, it would have been obvious to one of ordinary skill in the art that the anti-BCMA antibody, useful for treating cancer, of the first reference application and another therapy (i.e., for treating cancer) could be used in combination, as suggested by Brogdon, wherein said antibody and another therapy could be provided in a first and second kit, respectively, because Brogdon suggests combining BCMA-targeting therapy (i.e., CARs) with another therapy, wherein the single components of such a combination may be packaged in a kit or separately, and one of ordinary skill in the art would recognize that the individual components could be provided in separate kits for the treatment of cancer because combining prior art elements according to known methods would be expected to yield predictable results; one kit providing two active agents, which may be administered separately as suggested by Brogdon, would serve the same purpose as a first and second kit used to provide the same combination of active ingredients useful for the same purpose (i.e., treating cancer, specifically BCMA-expressing cancer).
This is a provisional nonstatutory double patenting rejection.
Claims 37-40 and 43 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 21, 28, and 64 of copending Application No. 18/256,422 (herein after referred to as "second reference application"). Although the claims at issue are not identical, they are not patentably distinct from each other.
Claim 1 of the second reference application discloses a protein-drug conjugate generally comprising an antigen-binding protein moiety and a drug conjugate moiety wherein the antigen-binding protein moiety comprises one or more antigen-binding fragments. Second reference application claim 21 discloses that, with regard to the protein-drug conjugate of claim 1, the one or more antigen-binding fragments each independently comprise HCDR1, HCDR2, and HCDR3, and the antigen-binding fragments may comprise amino acid sequences of SEQ ID NOs: 11, 26, and 42, respectively, and/or wherein the one or more antigen-binding fragments each independently comprise a VH comprising an amino acid sequence set forth in, for example, SEQ ID NO: 59. It is specifically noted that second reference application SEQ ID NOs: 11, 26, 42, and 59 are 100% matches to instant SEQ ID NOs: 26, 78, 136, and 251, respectively. Second reference application claim 28 further discloses that the protein-drug conjugate of claim 1 may further comprise an amino acid sequence set forth in, for example, SEQ ID NO: 68. It is specifically noted that second reference application SEQ ID NO: 68 is a 100% match to instant SEQ ID NO: 319. Second reference application claim 64 discloses a pharmaceutical composition comprising the protein-drug conjugate of claim 1 and a pharmaceutically acceptable carrier. Thus, the second reference application reads on the anti-BCMA antibody of instant claims 37-40 and the pharmaceutical composition of instant claim 43.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 44 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 21, 28, 64-65, and 69 of copending Application No. 18/256,422 (herein after referred to as "second reference application") in view of US 2016/0046724 A1 (herein after referred to as "Brogdon").
The disclosure of claims 1, 21, 28, and 64 of the second reference application are detailed above as pertain to instant claim 37. Additionally, claim 65 and 69 of the second reference application further discloses a method for treating diseases, comprising administering the protein-drug conjugate according to claim 1, wherein the protein-drug conjugate is optionally in combination with other therapies or drugs and the diseases are tumors or other diseases; wherein the tumors may be selected from, for example, lymphoma, multiple myeloma, and various other types of cancer. However, it is noted that the second reference application does not teach/suggest kits, including a first and second kit comprising an anti-BCMA antibody and additional antibody or pharmaceutical composition for treating cancer, respectively. This deficiency is remedied by Brogdon.
Brogdon discloses compositions and methods for treating diseases associated with BCMA expression and chimeric antigen receptors (CARs) specific to BCMA that comprise a BCMA binding domain (Abstract). It is further noted that the antigen-binding domains of the invention may be a human or humanized antibody or antibody fragment that specifically binds to BCMA (Paragraph 0031); “antibody fragment” refers to at least one portion of an intact antibody, or recombinant variants thereof, and refers to the antigen binding domain, e.g., an antigenic determining variable region of an intact antibody, that is sufficient to confer recognition and specific binding of the antibody fragment to a target, such as an antigen, wherein examples of antibody fragments include, but are not limited to, Fab, Fab′, F(ab′)2, and Fv fragments, scFv antibody fragments, linear antibodies, single domain antibodies such as sdAb (either VL or VH), camelid VHH domains, and multi-specific molecules formed from antibody fragments such as a bivalent fragment comprising two or more, e.g., two, Fab fragments linked by a disulfide bridge at the hinge region, or two or more, e.g., two isolated CDR or other epitope binding fragments of an antibody linked further wherein an antibody fragment can also be incorporated into single domain antibodies, maxibodies, minibodies, nanobodies, intrabodies, diabodies, triabodies, tetrabodies, v-NAR and bis-scFv (Paragraph 0176). In certain embodiments, the BCMA CAR molecules or the anti-BCMA binding domain of the invention include one, two, or three CDRs from the heavy chain variable region as provided in Table 22 (Paragraph 0086). It is specifically noted that the antibody designated as C9178-G4 from Table 22 comprises: (i) HCDR1 of sequence GFTFSSY; (ii) HCDR2 of sequence SGSGGS; and (iii) HCDR3 of sequence MGWSSGYLCAFDI; the bolded portions of the sequences correspond to sequence fragments comprised within instantly claimed SEQ ID NOs: 26, 78, and 136, respectively. Thus, Brogdon discloses CARs which comprise antigen binding domains, which may be an antibody or antibody fragment, wherein antibody fragments include single domain antibodies only comprising a VH/HCDRs1-3 (i.e., VHH antibody), wherein said antibody or antibody fragment is specific for BCMA and may comprise fragments of the instantly claimed HCDRs. Brogdon further discloses, in one embodiment, the cells expressing a CAR molecule, e.g., a CAR molecule described by the invention, may be administered in combination with an agent that treats the disease associated with BCMA, wherein exemplary diseases to be treated include cancer (i.e., a CAR molecule of the invention may be administered in combination with an agent that treats cancer) (Paragraphs 0073-0076). Brogdon specifically discloses methods for preventing relapse of cancer associated with BCMA-expressing cells, the methods comprising administering to a subject in need thereof an anti-BCMA CAR-expressing cell (e.g., BCMA CART cell or BCMA CAR-expressing NK cell) of the invention that binds to the BCMA-expressing cell wherein, in one aspect, the methods comprise administering to the subject in need thereof an effective amount of an anti-BCMA CAR-expressing cell (e.g., BCMA CAR-T cell or BCMA CAR-expressing NK cell) of the invention that binds to the BCMA-expressing cell in combination with an effective amount of another therapy (Paragraph 0699). It is noted that the term "combination" refers to either a fixed combination in one dosage unit form, or a combined administration where a compound of the present invention and a combination partner (e.g. another drug, also referred to as "therapeutic agent" or "co-agent") may be administered independently at the same time or separately within time intervals, especially where these time intervals allow that the combination partners show a cooperative, e.g. synergistic effect; the single components may be packaged in a kit or separately (Paragraph 0189; emphasis added). It is noted that while Brogdon does not explicitly mention an embodiment wherein the CAR molecule and another therapy are provided in a first and second kit, Brogdon does suggest that single components may be packaged in a kit or separately; thus, one of ordinary skill in the art would recognize that the individual components could be provided in separate kits for the treatment of cancer.
The second reference application and Brogdon are considered to be analogous to the present invention as they are in the same field of anti-BCMA antibodies/antigen binding domains and compositions thereof. Thus, it would have been obvious to one of ordinary skill in the art that the protein-drug conjugate, useful for treating cancer, of the second reference application and another therapy (i.e., for treating cancer) could be used in combination, as suggested by Brogdon, wherein said protein-drug conjugate and another therapy could be provided in a first and second kit, respectively, because Brogdon suggests combining BCMA-targeting therapy (i.e., CARs) with another therapy, wherein the single components of such a combination may be packaged in a kit or separately, and one of ordinary skill in the art would recognize that the individual components could be provided in separate kits for the treatment of cancer because combining prior art elements according to known methods would be expected to yield predictable results; one kit providing two active agents, which may be administered separately as suggested by Brogdon, would serve the same purpose as a first and second kit used to provide the same combination of active ingredients useful for the same purpose (i.e., treating cancer, specifically BCMA-expressing cancer).
This is a provisional nonstatutory double patenting rejection.
Claims 3, 40, and 43-44 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3-4, and 14-16 of copending Application No. 18/013,530 (herein after referred to as "third reference application"). Although the claims at issue are not identical, they are not patentably distinct from each other.
Claim 1 of the third reference application generally discloses a binding protein comprising at least two protein functional regions, wherein the binding protein comprises a protein functional region A and a protein functional region B, which target different antigens or different epitopes on the same antigen, wherein generally protein functional region A is of a Fab structure and protein functional region B is of a VH structure. Third reference application claim 3 further discloses that the antigen may be selected from a list including, for example, BCMA and wherein preferably the protein functional region A is a Fab derived from a PD-L1, HER2, B7H4, or BCMA antibody or antigen binding fragment thereof and protein functional region B is a VH derived from a CTLA4, 4-1BB, OX40, or BCMA antibody or antigen binding fragment thereof. Third reference application claim 4 further discloses that the BCMA antibody may comprise a VH, wherein the VH comprises HCDRs1-3 with amino acid sequences as set forth in SEQ ID NOs: 17, 39, and 61. It is specifically noted that third reference application SEQ ID NOs: 17, 39, and 61 are 85.7%, 80%, and 100% matches to instant SEQ ID NOs: 26, 78, and 136, respectively. Third reference application claim 14 discloses a pharmaceutical composition comprising the binding protein of claim 1 and a pharmaceutically acceptable carrier, wherein preferably the pharmaceutical composition further comprises an additional anti-tumor antibody as an active agent. Third reference application claims 15-16 are drawn to, respectively: (i) a kit comprising the binding protein of claim 1, which preferably includes a device for administering the protein or instructions for use; and (ii) a combination of kits comprising a kit I and a kit II, wherein the kit I comprises the binding protein of claim 1 and the kit II comprises an additional antibody or pharmaceutical composition. Thus, the third reference application reads on the anti-BCMA antibody of instant claims 37 and 40, the pharmaceutical composition of instant claim 43, and the kits of instant claim 44.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
Claims 37-48 are pending. Claims 41-42 and 45-48 are withdrawn. Claims 37-40 and 43-44 are rejected. No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALYSSA RAE STONEBRAKER whose telephone number is (571)270-0863. The examiner can normally be reached Monday-Thursday 7:00 am - 5:00 pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Samira Jean-Louis can be reached at (571)270-3503. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/ALYSSA RAE STONEBRAKER/Examiner, Art Unit 1642
/Laura B Goddard/Primary Examiner, Art Unit 1642