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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 2/3/2026 has been entered.
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. The present application is a CON of 17/471,206 and is drawn from PCT/US2018/60887, filed 11/14/2018; and claims benefit under 35 U.S.C. 119(e) to U.S. Provisional application 62/585780, filed 11/14/2017.
Status of Claims
Claims 1-18 are pending and are being examined on the merits.
Claim Rejections – Maintained
Claim Rejections - 35 USC § 103
Claim Interpretation
The following is a quotation of 35 U.S.C. 112(f):
(f) Element in Claim for a Combination. – An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art. The broadest reasonable interpretation of a claim element (also commonly referred to as a claim limitation) is limited by the description in the specification when 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is invoked.
As explained in MPEP § 2181, subsection I, claim limitations that meet the following three-prong test will be interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph:
(A) the claim limitation uses the term “means” or “step” or a term used as a substitute for “means” that is a generic placeholder (also called a nonce term or a non-structural term having no specific structural meaning) for performing the claimed function;
(B) the term “means” or “step” or the generic placeholder is modified by functional language, typically, but not always linked by the transition word “for” (e.g., “means for”) or another linking word or phrase, such as “configured to” or “so that”; and
(C) the term “means” or “step” or the generic placeholder is not modified by sufficient structure, material, or acts for performing the claimed function.
Use of the word “means” (or “step”) in a claim with functional language creates a rebuttable presumption that the claim limitation is to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites sufficient structure, material, or acts to entirely perform the recited function.
Absence of the word “means” (or “step”) in a claim creates a rebuttable presumption that the claim limitation is not to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is not interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites function without reciting sufficient structure, material or acts to entirely perform the recited function.
Claim limitations in this application that use the word “means” (or “step”) are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action. Conversely, claim limitations in this application that do not use the word “means” (or “step”) are not being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action.
Specifically, instant claim 1 recites “wherein the D domain comprises a means for binding to BCMA,” in line 3. The specifications disclose anti-BCMA DD polypeptides comprising the amino acid sequences of instant SEQ ID NOs: 11-306, in Table 1 (specifications, pg. 107). The broadest reasonable interpretation encompasses those specific anti-BCMA DD polypeptides disclosed in the specification, as well as equivalents thereof in the art, including generic anti-BCMA DD polypeptides.
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.
Claims 1-11 and 15-18 are rejected under 35 U.S.C. 103 as being unpatentable over Ali et al., (from IDS, Cite No. 1; Blood, 2016, 128(13)) and Lafleur (from IDS, Cite No. 16; WO 2016/164369; published 3/10/2016).
Ali et al. teaches T cells expressing an anti-BCMA CAR for treatment of multiple myeloma (title). Ali teaches multiple myeloma (MM) is an almost always incurable malignancy of plasma cells. Chimeric antigen receptors (CAR) are proteins that incorporate an antigen recognition domain, costimulatory domains, and T-cell activation domains; whereby T cells that express CARs specifically recognize and eliminate malignant cells expressing a targeted antigen (pg. 1688, col. 1). Ali teaches that appropriate target antigens for CAR T-cell therapies should be uniformly expressed on the malignancy and should not be expressed on normal essential cells; and that BCMA is only expressed by some B cells, plasma cells and malignant plasma cells, but is not expressed by hematopoietic stem cells, or by normal essential nonhematopoietic tissues (pg. 1688, col. 2). Ali generated an anti-BCMA CAR which incorporated an anti-BCMA single-chain variable fragment (scFv), a CD8 transmembrane domain, a CD28 costimulatory domain and the CD3-zeta T-cell activation domain (pg. 1690, col. 1, last paragraph - col. 2, top; see Fig. 1A, pg. 1689). Ali teaches the CAR T-cells were suspended in “complete medium” containing AIM-V CTS medium (Supplemental Methods; pg. 1, para. 1- pg. 2). Thus, the composition of Ali comprises a liquid medium. Ali teaches administering the anti-BCMA CAR T-cells in a clinical trial for the treatment of MM in human patients (abstract). Ali concludes “we have shown that CAR-BCMA T cells have powerful activity against MM that was resistant to standard therapies; these results should encourage further efforts to enhance anti-BCMA CAR T cell therapies.” Further, that the striking results indicate that “CAR T cells targeting BCMA have great potential to be an effective new treatment of MM; and further development of anti-BCMA CAR T-cell therapies is a very promising area of research,” (pg. 1698, col. 2, para. 4). Thus, Ali teaches a CAR construct comprising an anti-BCMA binding domain; however, Ali uses an anti-BCMA scFv polypeptide and does not teach wherein the CAR comprises an anti-BCMA D-domain polypeptide.
Lafleur teaches de novo binding domain polypeptides (DBDpp) that specifically bind a target of interest, including nucleic acids encoding the DBDpp and host cells; as well as therapeutic applications (abstract). Lafleur teaches the DBDpp are produced off of a reference scaffold having SEQ ID NO: 1 (the α3d scaffold; pg. 41, para. 00121), wherein the scaffold peptide is a non-naturally occurring, targetless antiparallel three helical bundle reference polypeptide (pg. 12, para. 0039); whereby variant polypeptides containing modifications of the reference scaffold are able to specifically bind targets of interest. Specifically, “the structural constraints of the surface exposed residues (that can be modified) confer the ability of the surface exposed residues to specifically bind a target of interest,” (pg. 13, para. 0039, last sentence). Lafleur teaches the base scaffold sequence of the DBDpp is that of SEQ ID NO: 4 (pg. 162, claim 1), in which the target-specific modifiable amino acids are marked with an X. For comparison, the base scaffold of Lafleur SEQ ID NO: 4 is aligned with the anti-BCMA D-domain polypeptide of instant SEQ ID NO: 11; see Fig. 1 below. It is apparent that the only resides that are different in instant SEQ ID NO: 11 occur at the modifiable residues of Lafleur’s DBDpp scaffold. Thus, the examiner asserts that the “DBD” scaffold polypeptides of Lafleur are equivalent to the generic “D-domain” polypeptides of the instant application; thus Lafleur teaches D-domain polypeptides.
[AltContent: textbox (Fig. 1: Comparison of the amino acid sequences of the DBD scaffold polypeptide of Lafleur (top) with the anti-BCMA D-domain polypeptide of instant SEQ ID NO: 11 (bottom). “X” residues represent the modifiable residues to confer binding target specificity, as taught by Lafleur.
[img-media_image1.png])]
Lafleur teaches a method of transforming a reference polypeptide into a polypeptide having specific binding for a target of interest comprising modifying a plurality of amino acid residues in the reference polypeptide, generating a candidate library of polypeptides, and screening the candidate library for binding polypeptides that exhibit specific binding to the target of interest (pg. 163, claim 12). Lafleur demonstrates the applicability of this method by generating various target-specific embodiments of the DBDpp, wherein about 45 variant DBDpp are generated across 7 different binding targets; including CD137, CD47, CTLA4, DR5, KIR, PD-L1, TIM3, and PD-1 (pg. 124, Table 1).
Lafleur teaches that the DBDpp of the invention may be incorporated into fusion proteins, wherein the DBDpp and any polypeptide of interest can be operably linked to form a DBDpp fusion protein (pg. 68, para. 00177); and wherein the polypeptide of interest can be a serum protein (e.g., albumin); and wherein the fusion protein may additionally contain linkers (pg. 68, para. 00176). Lafleur teaches wherein the fusion protein comprises a chimeric antigen receptor (CAR; pg. 80, para. 00208). Lafleur teaches “provided herein are methods for creating DBDpp-CAR, their use in creating chimeric cells, such as human T cells, and the use of these chimeric T cells in adoptive immunotherapy (pg. 81, para. 00212). Lafleur teaches “depending on the desired antigen to be targeted, the DBDpp-CAR can be engineered to include the appropriate antigen binding DBDpp that is specific to the desired antigen target,” (pg. 81, para. 00210). Lafleur teaches examples of tumor antigens that can be specifically bound by a DBDpp in a DBDpp-CAR (pg. 82, para. 00213), which include BCMA. Thus, Lafleur teaches methods to generate an anti-BCMA DBDpp and the use of the anti-BCMA DBDpp in a CAR, for use as a cancer therapeutic.
Regarding the CAR construct; Lafleur teaches that the transmembrane domain may comprise CD8 (pg. 84, para. 00218); the intracellular signaling domain may be CD3-zeta or a 4-1BB signaling domain, by itself or combined with another cytoplasmic domain (pg. 81, para. 00209; pg. 85, para. 00222). Lafleur teaches the co-stimulatory domain can be CD27 or CD28, or others (pg. 86, para. 00225).
Regarding therapeutic applications, Lafleur teaches the DBDpp-CAR-modified T cells as a pharmaceutical composition (pg. 144, para. 00401), which refers to compositions, carriers, diluents and reagents that are capable of administration to a human (pg. 35, para. 0099); and thus includes liquid compositions. Lafleur teaches therapeutic compositions containing the DBDpp-CARs can be used to treat a particular cancer, including non-solid tumors, for example leukemias, lymphocytic leukemia, or multiple myeloma (pg. 142, paras. 00393-00394); or more generally, to treat B-cell associated diseases (pg. 143, para. 00397). Lafleur teaches wherein the therapeutic use comprises administering, either alone, or as a pharmaceutical composition, the DBDpp-CAR-modified T cells (pg. 144, para. 00401).
It would have been obvious to one of skill in the art to modify the anti-BCMA CAR of Ali et al to comprise an anti-BCMA D-domain in place of the anti-BCMA scFv. One would have been motivated to do so given the knowledge that BCMA is uniformly expressed by malignant plasma cells and has limited expression in normal essential cells and tissues, and as such, that anti-BCMA CAR T cells have powerful activity against multiple myeloma and B-cell malignancies, as taught by Ali et al. There would have been a reasonable expectation for success given that an anti-BCMA DBDpp (i.e. D-domain polypeptide) can be generated using the methods of Lafleur, and that the anti-BCMA DBDpp can be used as the extracellular TAA antigen-binding domain of a CAR, for use as a therapeutic for a B-cell mediated disease, as taught by Lafleur. Thus, the invention was prima facie obvious to one of ordinary skill in the art at the time the invention was made.
Regarding claims 1-11, the combination anti-BCMA CAR of Ali and Lafleur is described above. Ali teaches the anti-BCMA CAR can be expressed in modified T cells which are comprised in a complete media for administration to patients; thus making obvious a liquid medium comprising a protein comprising an anti-BCMA D domain of claim 1; or wherein the protein is a CAR, of claim 2. Ali teaches the CAR comprises a transmembrane domain, wherein the transmembrane domain is a CD8 transmembrane domain; and thus makes obvious instant claims 3-5. Ali teaches the CAR comprises an intracellular signaling domain of a T cell receptor (i.e. CD3) zeta domain and an intracellular co-stimulatory CD28 domain; thus making obvious instant claims 6-8 and 10-11. Lafleur teaches that the CAR may comprise a 4-1BB intracellular signaling domain, thus making obvious instant claim 9.
Regarding claims 15-18; the combination anti-BCMA CAR of Ali and Lafleur is described above. Ali teaches that anti-BCMA CAR may be expressed in modified T cells, which may be administered to a patient in a method of treating multiple myeloma; thus making obvious the method of treating a B-cell mediated disease of instant claim 15, a B-cell malignancy of instant claim 16, and wherein the malignancy is multiple myeloma of instant claim 18. Lafleur teaches the modified anti-BCMA CAR-expressing T cells may be administered in a method for treating lymphocytic leukemia, thus making obvious instant claim 17.
Claims 12-14 are rejected under 35 U.S.C. 103 as being unpatentable over Ali et al., (from IDS, Cite No. 1; Blood, 2016, 128(13)) and Lafleur (from IDS, Cite No. 16; WO 2016/164369; published 3/10/2016) as applied to claims 1-11 and 15-18 above, and further in view of Nielsen et al., (US 2011/0293579; published 12/1/2011).
The combination composition comprising modified T cells expressing an anti-BCMA CAR of Ali and Lafleur is described above. However, Ali and Lafleur do not teach wherein the anti-BCMA CAR comprises an AFP p26 polypeptide.
Nielsen et al. teaches bispecific fusion proteins with therapeutic uses (abstract). Nielsen teaches the bispecific fusion proteins comprise (a) a targeting domain, (b) an activator domain, and (c) a half-life modulator (pg. 1, para. 0009; pg. 38, claim 6). Regarding the half-life modulator, Nielsen teaches that bispecific proteins may not exhibit optimal serum half-lives and that it may be desirable to modulate the half-life of the bispecific proteins (pg. 17, para. 0318). Nielsen teaches several potential half-life modulators for use in the bispecific fusion protein, including human serum albumin, a vitamin D-binding protein, a human transthyretin (TTR) amino acid sequence, and others (pg. 18; pg. 39, claim 18). In some embodiments, the half-life modulator comprises at least 100 consecutive amino acids of a human alpha-fetoprotein (AFP) amino acid sequence (pg. 18, para. 0324). In some embodiments the AFP half-life modulator comprises the sequences of SEQ ID NOs: 29, 68 or 69 (pg. 39, claim 20); or the nucleic acid sequence of SEQ ID NO: 216, which corresponds to the amino acid sequence of SEQ ID NO: 69 (pg. 6, para. 0185). Nielsen teaches the AFP half-life modulator comprises at least 100 consecutive amino acid sequences of SEQ ID NO: 29; which comprises the AFP fragment of SEQ ID NO: 69 in full. For comparison, the instant specifications describe the use of the anti-BCMA DD polypeptide in a fusion protein, wherein the fusion protein comprises a p26 protein of SEQ ID NO: 969; teaching “such fusion proteins containing p26 sequences have been discovered herein to have surprisingly long serum half-life,” (specs, pg. 44, para. 0143). Instant SEQ ID NO: 969, encoding a fragment of AFP, is 204 amino acids in length, and has 100% amino acid sequence identity to the corresponding fragment of Nielsen SEQ ID NO: 69, of the AFP half-life modulator. Nielsen teaches the half-life modulator may be joined to the targeting polypeptide domain via a peptide bond (pg. 17, para. 0319).
It would have been obvious to one of skill in the art to modify the combination anti-BCMA CAR of Ali and Lafleur to further comprise a serum AFP p26 polypeptide. One would have been motivated to do so given that inclusion of an AFP p26 polypeptide increases half-life of the protein, as taught by Nielsen et al. There would have been a reasonable expectation for success given that the AFP polypeptide can be joined to a targeting polypeptide by a peptide bond, as taught by Nielsen et al.; and that the BCMA DBDpp can be a fusion protein whereby the BCMA DBDpp is fused, with or without a linker, to a serum polypeptide of interest, as taught by Lafleur et al. Thus, the invention was prima facie obvious to one of skill in the art at the time the invention was made.
Regarding claim 12, the compositions comprising T cells expressing the anti-BCMA CAR of the combination of Ali and Lafleur is described above. The AFP half-life modulator of Nielsen SEQ ID NO: 69, comprises an AFP p26 polypeptide; specifically, it comprises the AFP p26 protein of instant SEQ ID NO: 969. Thus, the combination CAR of Ali, Lafleur and Nielsen makes obvious instant claim 12.
Regarding claims 13 and 14, Nielsen teaches the AFP half-life modulator comprises at least 100 consecutive amino acids that are identical to AFP sequence of SEQ ID NO: 29, or SEQ ID NO: 69, which is a smaller fragment of SEQ ID NO: 29. The AFP p26 polypeptide of instant SEQ ID NO: 969 is 204 consecutive amino acids, with 100% sequence identity, of Nielsen SEQ ID NO: 69. Thus, it would have been obvious to one of skill in the art to use a smaller fragment of the AFP polypeptide of Nielsen, whereby the fragment consists of 204 amino acid residues, for the same purpose (i.e. increased half-life) as taught by Nielsen. As Nielsen teaches embodiments of the AFP half-life modulator may be any 100 consecutive amino acid fragment of the larger polypeptide of SEQ ID NO: 69, and the AFP p26 polypeptide of instant SEQ ID NO: 969 is an identical, 204 amino acid fragment; the obviousness of using a smaller fragment of AFP “consisting of” only the 204 amino acids is a matter of routine optimization; see MPEP Section 2144.05(II). There would have been a reasonable expectation for success given that the smaller AFP p26 fragment is being used for the same purposes as the AFP polypeptides of Nielsen et al. Thus, the combination compositions comprising an anti-BCMA CAR of Ali and Lafleur, wherein the CAR further comprises the AFP p26 fragment of Nielsen as a half-life modulator, wherein the AFP p26 fragment consists of the 204 amino acids of instant SEQ ID NO: 969, makes obvious the compositions of instant claims 13-14.
Response to Arguments
Applicant's arguments filed 2/3/2026 have been fully considered but they are not persuasive. Applicants contend that Ali et al. does not disclose D-domains, and that LaFleur fails to remedy this deficiency (remarks, pg. 4, para. 3). Applicants acknowledge the use of “means-plus function” language of independent claim 1, and that such language must be construed consistent with 35 U.S.C. 112(f); whereby the means-plus function language serves the purpose of limiting the scope of the claim to the particular structure disclosed, together with equivalents. Thus, applicants contend that, when properly construed, claim 1 does not encompass all D-domains that bind to BCMA, but only the particular structures disclosed in the applicant’s specification that have the recited function and equivalents thereto (remarks, pg. 4, para. 3). Thus, applicants contend that the “equivalents” aspect of anti-BCMA D-domains only applies to particular structures disclosed in the specifications that have the recited function and equivalents thereto (remarks, pg. 4, para. 3). Further, applicants contend that when applying an obviousness rejection, Office personnel must therefore ensure the written record includes the factual inquires; specifically, ascertaining the differences between the claimed invention and the prior art (remarks, pg. 5, full). Applicants contend that the Office has failed to ascertain the differences, and in doing so, has failed to properly notify applicant of the reasons for rejection so that applicant can decide how to best proceed (remarks, pg. 6, para. 2). That the examiner, by asserting an “product-by-process” rationale, without describing the differences between the prior art and the claimed invention, has not construed the relevant feature of claim 1 in a manner that enables Applicant to understand the Office’s determination of the scope of the claim. Thus, the Office has failed to establish a prima facie case of obviousness (pg. 6, para. 3).
Regarding the Office action of 7/15/2025, applicants contend that Examiner’s reference to the following language from MPEP 2183 does not absolve the issue of not identifying the differences between the claimed subject matter and the prior art (pg. 6 – pg. 7).
IF NONEQUIVALENCE SHOWN, EXAMINER MUST CONSIDER OBVIOUSNESS
However, even where the applicant ... has shown that the prior art element is not
equivalent to the structure, material or acts described in the applicant's specification, the
examiner must still make a 3 5 U.S. C. 103 analysis to determine if the claimed means- ( or
step-) plus-function would have been obvious from the prior art to one of ordinary skill in
the art. Thus, while a finding of nonequivalence prevents a prior art element from
anticipating a means- ( or step-) plus-function limitation in a claim, it does not prevent the
prior art element from rendering the claim limitation obvious to one of ordinary skill in
the art. Because the exact scope of an "equivalent" may be uncertain, it would be
appropriate to apply a 35 U.S.C. 102/103 rejection where the balance of the claim
limitations are anticipated by the prior art relied on. A similar approach is authorized in
the case of product-by-process claims because the exact identity of the claimed product
or the prior art product cannot be determined by the examiner.
Applicants contend the above language does not provide sufficient justification for an obviousness rejection for three reasons (remarks, pg. 7 – pg. 8):
The Office still needs to explain the differences between the claimed subject matter and the prior art.
The Office’s position regarding applying a 102/103 rejection is inapplicable here, as the Office is not applying a 102/103 rejection.
The product-by-process language is in reference to product-by-process claims, and does not give license to reject a claim based on an alleged product-by-process embodiment in the prior art.
Applicants contend that claims 1-11 and 15-18 are not made obvious over Ali and Lafleur, as described above, and therefore the obviousness cannot be extended to Nielsen, in claims 12-14 (remarks, pg. 8, bottom).
In response the examiner will first address the applicant’s contention that means-plus-function language limits the scope to only those particular structures of the specifications and equivalents; and that claim 1 does not encompass all D-domains that bind to BCMA. The examiner disagrees. Claim 1 recites “wherein the D domain comprises a means for binding to BCMA.” As discussed above, Lafleur defines D domain polypeptides as a non-antibody scaffold having 73 amino acid residues, whereby 13 residues are variable (X residues), which can be any amino acid, and that the 13 variable residues impart the binding specificity of the D domain polypeptide to any particular target. Thus, as D domain scaffolds are known in the art. Therefore, the claim limitation of a “D domain comprising a means for binding to BCMA”, when given its broadest reasonable interpretation, does encompass all D-domains that bind to BCMA. The examiner cannot conceive of an anti-BCMA D-domain polypeptide that is not encompassed by the claim language. Further, the scope of all D-domains that bind to BCMA encompasses those anti-BCMA D-domains that are presently unidentified. More specifically, the scope encompasses a genus of anti-BCMA D-domain peptides, comprised in the protein/composition of claim 1, including any anti-BCMA D-domain peptides presently in the art, and any anti-BCMA D-domain peptides that are disclosed in the future. At any point in time, the skilled artisan will envision any anti-BCMA D-domain peptide as reading on “a D domain comprising a means for binding BCMA”. Therefore the “equivalents” for such D-domain polypeptides extend beyond the ~300 particular structures (i.e. species) of the specifications to encompass the claimed genus of anti-BCMA D-domain polypeptides. In this manner, the “means for binding BCMA” language includes those particular structures described in the specifications, as representative species, but does not limit the claimed genus to only those species that are described.
Regarding applicant’s contention that the examiner has not ascertained the differences between the claimed invention and the prior art in accordance with the factual inquires of an obviousness rejection, the examiner points out that there are two points of “obviousness” applied to the claims; the obviousness of the invention and the obviousness of equivalents to the anti-BCMA D-domain polypeptides. The rejection for obviousness under U.S.C. 103 is applied to the composition of claim 1, the CAR proteins of claims 2-11 and methods of treating of claims 15-18. The examiner highlighted that Ali teaches anti-BCMA CAR constructs, compositions and methods, wherein the anti-BCMA binding domain is an scFv, however Ali does not teach wherein the anti-BCMA binding domain is a D-domain polypeptide. Thus, the examiner has ascertained the differences between the claimed invention and the prior art references that are relied on for making the claimed invention obvious. Instead, the examiner surmises that the basis of the applicant’s arguments over obviousness are centered on the “equivalents” component of the interpretation of “means-plus function” language under 112(f); more specifically, pertaining to the arguments of the Office Action of 7/15/2025. To review, in that Office Action, the examiner stated:
Section 2183 of the MPEP discusses making a prima facie case of equivalence. Section 2183 states that if the examiner finds that a prior art element (A) performs the function specified in the claims, (B) is not excluded by any explicit definition provided in the specification for an equivalent, and (C) is an equivalent of the means-plus function limitation; the examiner should provide an explanation and rationale in the Office action as to why the prior art element is an equivalent. Factors that will support a conclusion that the prior art element is an equivalent are: (A) the prior art element performs the identical function specified in the claim in substantially the same way and produces substantially the same results as the corresponding element disclosed in the specification, (B) a person of ordinary skill in the art would have recognized the interchangeability of the element shown in the prior art for the corresponding element disclosed in the specification, or (C) there are insubstantial differences between the prior art element and the corresponding element disclosed in the specification. MPEP section 2183 states “a showing of a least one of the above-noted factors by the examiner should be sufficient to support a conclusion that the prior art element is an equivalent.” Here the examiner highlights that the Lafleur reference teaches D-domain scaffolds and how to make D-domain peptides that specifically bind to BCMA, as described above. The applicants used the teachings of Lafleur to screen for ~300 alternative, yet equivalent, anti-BCMA D-domain polypeptides (see specs. pg. 165, para. 0429; WO2016164305, to Lafleur et al., and WO2016164369, to Lafleur). So, the question is whether an as-of-yet unidentified anti-BCMA D-domain polypeptides, produced following the guidance of Lafleur, also qualify as equivalents under the means-plus-function interpretation under 112(f). To this point, the examiner highlights the last paragraph of MPEP Section 2183: If nonequivalence shown, examiner must consider obviousness. “However, even where the applicant has met the burden of proof and has shown that the prior art element is not equivalent to the structure described in the applicant’s specification, the examiner must still make a 35 U.S.C. 103 analysis to determine if the claimed means-plus-function would have been obvious from the prior art to one of ordinary skill in the art. Thus, while a finding of nonequivalence prevents a prior art element from anticipating means-plus-function limitation in a claim, it does not prevent the prior art element from rendering the claim obvious to one of ordinary skill in the art. Because the exact scope of an “equivalent” may be uncertain, it would be appropriate to apply a 35 U.S.C. 102/103 rejection where the balance of the claim limitations are anticipated by the prior art relied upon. A similar approach is authorized in the case of product-by-process claims because the exact identity of the claimed product or the prior art product cannot be determined by the examiner.” In this case, the examiner is using the teachings of Lafleur, of product-by-process anti-BCMA D-domain peptides as making obvious equivalent anti-BCMA D-domain peptides, even in the case whereby the products of Lafleur’s process are not considered to anticipate the ~300 anti-BCMA D-domain peptides of the specifications. The examiner is applying the means-plus-function interpretation under 112(f) as including the product-by-process anti-BCMA D-domain peptides of Lafleur as obvious, not anticipated, equivalents in the art under 35 U.S.C. 103, of claim 1; whereby they would also make obvious the invention of instant claims 2-18 over the anti-BCMA CAR of Ali, in view of the half-life modulator of Nielsen, as described above.
The specification describes the selection of the ~300 anti-BCMA D-domain polypeptides via screening the library of variant D-domain polypeptides for those that bind BCMA. As D-domain polypeptides, and the library of variants of Lafleur, were prior art, the examiner is applying product-by-process variant anti-BCMA D-domain polypeptides from the methods/library of Lafleur as equivalents. Thus, the examiner is determining that said equivalents are in accordance with MPEP 2183 (A)(B) and (C). Regarding the factors that support the conclusion, the examiner determines that the prior art element performs the identical function as the corresponding element disclosed in the specification, and that a person of ordinary skill in the art would have recognized the interchangeability of the element. However, in describing the differences between the claimed structures and the equivalents produced by the process/methods/library of Lafleur, the equivalents of the product-by-process of Lafleur do not have an explicitly defined structure for comparison. Therefore the examiner takes guidance from the “Nonequivalence” paragraph; though it is noted that applicants have not shown the prior art element is not equivalent, and examiner is not considering the variant product-by-process anti-BCMA D-domain polypeptides of Lafleur to be nonequivalent. Rather, the paragraph discusses that equivalents are not limited to those structures that anticipate, rather it also encompasses obvious equivalents in a means-plus-function claim, which may arise from product-by-process structures, where “the exact identity of the prior art product cannot be determined by the examiner.”
Therefore, regarding applicant’s contention that the examiner has not ascertained the differences between the claimed subject matter and the prior art, the examiner has established that the “exact identity of the prior art product” cannot be determined, and therefore an explicit comparison of structure is not made. However, the examiner reviews the fact pattern to highlight the differences that can be made. Lafleur teaches D-domain polypeptides are based on a scaffold, with 73 total amino acids, of which 60 amino acids are fixed and 13 amino acid residues are variable (X residues) and can be any amino acid or combination, which imparts the binding specificity of the D-domain polypeptide. Lafleur teaches that a library of numerous variations of the scaffold was created, and the library can be applied in a phage display format to identify the D-domain variants that bind to a target of interest. The 300 embodiments of the instant anti-BCMA D-domain polypeptides comprise the scaffold(s) of Lafleur, and were generated by screening the library of generated variant D-domain polypeptides, as described by Lafleur and in the instant specifications (see specs. pg. 165, para. 0429; WO2016164305, to Lafleur et al., and WO2016164369, to Lafleur). Thus, the differences between the ~300 anti-BCMA D-domain polypeptides of the specifications and those produced by the method of Lafleur amount to screening for alternative polypeptides, from the library of Lafleur, which bind to BCMA. Structurally, all the embodiments comprise the same scaffold amino acid residues of Lafleur, and the variant anti-BCMA D-domain polypeptides of Lafleur would be expected to have some different combination of amino acid residues at the variable X positions of the scaffold, similar to the differences between the ~300 embodiments of the instant specifications. As described above, the scope of the mean-plus-function language encompasses all D-domain polypeptides which bind to BCMA, whether identified or unidentified, as the claim encompasses the genus of anti-BCMA D-domain polypeptides. Any other anti-BCMA D-domain polypeptide, which may be derived from the library (or methods) of Lafleur, would necessarily comprise the same scaffold amino acids and different amino acid residues in the variable X locations of the scaffold, in the same manner as the ~300 different variants of the specifications. Thus, as each of the ~300 different anti-BCMA D-domain polypeptides of the instant specifications are equivalents to each other, despite differences in explicit amino acid sequence, so too would any other anti-BCMA D-domain polypeptides derived from the library (or methods) of Lafleur be equivalents thereto.
The examiner highlighted the language of section 2183 of the MPEP for guidance regarding equivalents generated from product-by-process limitations. The examiner is not making a case for nonequivalents, rather the examiner specifically iterated the final sentence: A similar approach is authorized in the case of product-by-process claims because the exact identity of the claimed product or prior art product cannot be determined by the examiner. Thus, the context of the language is that it is not (always) possible for the examiner to ascertain the precise structural differences between products-by-process, but rather that products that are derived from the same process may be obvious equivalents, even if the precise structure is not known. To summarize, the examiner considers the scope of anti-BCMA D-domain polypeptides, having a means for binding BCMA, as encompassing a genus of anti-BCMA D-domain polypeptides, which encompasses more than the ~300 embodiments described in the specifications, including as-of-yet unidentified anti-BCMA species. The examiner considers any alternative anti-BCMA D-domain polypeptides derived from the product-by-process methods, i.e. screening a library of D-domain polypeptide variants for binding affinity to BCMA, of Lafleur, to be equivalents to the ~300 species of anti-BCMA D-domain polypeptides of the instant specifications, and to be encompassed within the genus of anti-BCMA D-domain polypeptides claimed by the mean-plus-function language of instant claim 1.
Regarding the contention that the Office’s position regarding applying a 102/103 rejection is inapplicable here, the examiner is not applying a 102/103 rejection. The context of the paragraph was referring to “obvious-type” equivalents. The guidance is that if it requires an obviousness rationale to make the species equivalents, and all the other prior art references otherwise anticipate the claim limitations, then a 102/103 rejection is applied. Here all the other prior art references do not anticipate the claim limitation, thus there is no basis for anticipation or a 102/103 rejection. The MPEP paragraph recited above is regarding nonequivalence and obviousness, it is not a rationale for applying a 102/103 rejection; rather it suggests that a 102/103 rejection may be appropriate in certain circumstances. Thus, the applicant’s contention that the Office’s position for applying a 102/103 rejection is inapplicable is unpersuasive. The Office is not applying a 102/103 rejection, the position the office is relying on is the product-by-process guidance of MPEP 2183 regarding the obviousness of equivalents in mean-plus-function claims. Regarding the contention that the product-by-process language may only be applied to product-by-process claims, and not to embodiments in the art; the examiner disagrees. The language is: A similar approach is authorized in the case of product-by-process claims because the exact identity of the claimed product or prior art product cannot be determined by the examiner. The context of the paragraph is about determining equivalents from product-by-process methods, whether said methods are in the examined claims or whether said methods are prior art which might apply to the claims being examined.
In conclusion the examiner does not find the applicant’s arguments persuasive, and the rejections are maintained on the basis that the means-plus-function language encompasses a genus of anti-BCMA D-domain polypeptides, and that alternative anti-BCMA D-domain polypeptides derived from the product-by-process methods/libraries of Lafleur are equivalents to species recited in the specifications and are encompassed within the claimed genus.
Claim Rejections – New
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 1-18 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Independent claim 1 is drawn to a composition comprising a liquid medium and a protein comprising a D domain, wherein the D domain comprises a means for binding to BCMA. The “means for” language invokes 112(f), and is interpreted as being drawn to a genus of anti-BCMA D-domain polypeptides, as described above, wherein the anti-BCMA D-domain polypeptides are comprised in a protein, which is comprised in a composition, of claim 1. No specific species or structure of the D-domain is recited in the claims, only that it comprises a means for binding to BCMA. Thus the claim encompasses a genus of unidentified anti-BCMA D-domain polypeptides.
The Guidelines for the Examination of Patent Applications Under the 35 U.S.C. 112, first paragraph, "Written Description" Requirement make clear 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, 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, Friday January 5, 2001, see especially page 1106 3rd column, revised Mar 25, 2008).
In support of the claimed genus of anti-BCMA D-domain polypeptides, the specification disclose ~300 embodiments, listed in Table 1 (specs. pg. 107), SEQ ID NOs: 11-306. Each of the species is based on a non-specific “scaffold” for generating D-domain polypeptides. Example 1 (pg. 165, para. 0429), describes the isolation and characterization of the D-domain polypeptides (DDpp), including those that bind BCMA. Specifically, the specifications disclose that “A DDpp library prepared as described in Intl. Appl. Publ. Nos. WO2016164305 and WO2016164369” (to Lafleur et al.), and the libraries were screened for phage that bind BCMA, CD123, AFP or AFP p26 through multiple rounds of selection. When looking to Lafleur et al. (WO ‘369), Lafleur teaches that a DDpp comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 2-5 (‘369; pg. 15, para. 0041). Each of Lafleur SEQ ID NOs: 2-5 is a DDpp scaffold, comprising 73 amino acids, whereby 13 amino acid residues are variable (X residues), which may be substituted with any amino acid, in any combination, and which impart the binding specificity of the DDpp as a whole (pg. 39, paras. 00115-00117). Further, Lafleur teaches the DDpp are represented by a mixed population, or library, of different DDpp molecules, wherein the library may have up to 1020 different DDpps (pg. 102, para. 00277). Laflelur teaches, for example, a polypeptide for binding a target of interest, comprising the amino acid sequence of MGSWX5EFX8X9RLX12AIX15X16RLX19ALGGSEAELAAFEKEIAAFESELQAYKGKGNPEVEX55LRX58X59AA X62RX65 X66LQAYRHN (SEQ ID NO: 4);
wherein Xn is a natural or non-natural amino acid; wherein each Xn is the same or different natural or non-natural amino acid (pg. 15, para. 0041).
The amino acid sequence of Lafleur SEQ ID NO: 4 is compared to the amino acid sequence of the anti-BCMA DDpp of instant SEQ ID NO: 11 below.
[AltContent: textbox (Fig. 1: Comparison of the amino acid sequences of the DBD scaffold polypeptide of Lafleur (top) with the anti-BCMA D-domain polypeptide of instant SEQ ID NO: 11 (bottom). “X” residues represent the modifiable residues to confer binding target specificity, as taught by Lafleur.
[img-media_image1.png])]
The claims require each member of the genus to have a binding function of binding BCMA. Lafleur discloses that SEQ ID NO:1, from which the scaffold of SEQ ID NOs: 2-5 are derived, and which comprises SEQ ID NO: 4, has no known binding partner (pg. 145, para. 00406). Lafleur teaches construction of different DBDpp (novo binding domain (DBD) containing polypeptide; pg. 2, para. 0007) libraries by random mutation of specific solvent exposed amino acid sequence positions of SEQ ID NO:1 and then screening for binders of a target using the DBDpp libraries (Example 2, para. 00406). The specification shows that some binders to different antigens can be identified and isolated from the DBDpp libraries, including the library based on SEQ ID NO:4 (F3 library) (see Tables 3-5). However, the identified binders of the instant specifications, Table 1: SEQ ID NOs: 11-306 (specs. pg. 107), are not considered representative species of the genus as the genus (at least the F3 library based on SEQ ID NO: 4) has a size of about 8x1016 (2013, simultaneous randomize thirteen Xs with 20 natural amino acids) or larger (simultaneous substitution all Xs with both natural amino acids and non-natural amino acids). 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 instant case, one of ordinary skill in the art cannot predict/envision the structures of other members of the genus based on the disclosed species because there is unpredictability in the results obtained from species other than those specifically disclosed and the claimed genus encompasses a vast number of structurally different species.
While the specification discloses methods for screening binders using the library, it does not provide sufficient written description as to the structures of the isolated binders (the claimed genus). It is duly noted that the written description provision of 35 U.S.C § 112 is severable from its enablement provision.
The purpose of the “written description” requirement is broader than to merely explain how to “make and use”; the applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the “written description” inquiry, whatever is now claimed.
In the instant case, each member of the genus may have a completely different binding specificity (i.e. binding to a different target) and each member has to be identified from the library by empirical testing. The Court has held that the disclosure of screening assays and general classes of compounds was not adequate to describe compounds having the desired activity: without disclosure of which peptides, polynucleotides, or small organic molecules have the desired characteristic, the claims failed to meet the description requirement of § 112. See University of Rochester v. G.D. Searle & Co., lnc., 69 USPQ2d 1886,1895 (Fed. Cir. 2004).
The claims are drawn to a genus that does not have a particularly identifying structural feature that correlates with a particular function. A description of one member having a particular structure and a particular binding specificity gives no information about other members that may be identified/isolated from the libraries, as such the isolated species cannot be considered representative of the genus claimed.
The specification does not provide sufficient written description as to the correlation between a structural feature and the desired function (binding to a target). There is no information regarding what structural features would likely be associated with the desired function. Although all members share partial structure, the shared partial structure (unmodified scaffold sequence) does not correlate to the binding function, as evidenced by the fact that SEQ ID NO: 1 does not have any known binding partner. For example, in Table 5 of Lafleur, SEQ ID NOs: 36 and SEQ ID NO: 40 both comprise SEQ ID NO:4 (i.e. identified from library F3). However, SEQ ID NO: 36 binds to KIR, whereas SEQ ID NO: 40 binds to PDL1. Given that there is no known correlation between any structural component and function, one of ordinary skill in the art would not be able to predict/envision which members among the genus having a size of 1016 or larger would have the desired binding function.
Protein chemistry is probably one of the most unpredictable areas of biotechnology. It is known in the art that the relationship between the amino acid sequence of a protein (polypeptide) and its tertiary structure (i.e. its binding activity) are not well understood and are not predictable (see Ngo et al., in The Protein Folding Problem and Tertiary Structure Prediction, 1994, Merz, et al., (ed.), Birkhauser, Boston, MA, pp. 433 and 492-495). There is no recognition in the art that sequence with identity predicts biological function. It is known in the art that even single amino acid changes or differences in a protein's amino acid sequence can have dramatic effects on the protein's function. For example, conservative replacement of a single “lysine” reside at position 118 of acidic fibroblast growth factor by “glutamic acid” led to the substantial loss of heparin binding, receptor binding and biological activity of the protein (Burgess et al., J of Cell Bio. 111:2129-2138, 1990). In transforming growth factor alpha, replacement of aspartic acid at position 47 with alanine or asparagine did not affect biological activity while replacement with serine or glutamic acid sharply reduced the biological activity of the mitogen (Lazar et al. Molecular and Cellular Biology 8:1247-1252, 1988). These references demonstrate that even a single amino acid substitution or what appears to be an inconsequential chemical modification will often dramatically affect the biological activity and characteristic of a protein. While it is known that many amino acid substitutions are possible in any given protein, the position within the protein's sequence where such amino acid substitutions can be made with reasonable expectation of success are limited. Certain positions in the sequence are critical to the three-dimensional structure/function relationship, and these regions can tolerate only conservative substitutions or no substitutions. Residues that are directly involved in protein functions such as binding will certainly be among the most conserved (Bowie et al. Science, 247:1306-1310, 1990, p. 1306, col.2).
The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed" (MPEP 2163.02), because the relevant identifying characteristics of the genus such as structure or other physical and/or chemical characteristics of the claimed genus are not set forth in the specification as-filed, commensurate in scope with the claimed invention. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method for isolating it. See Fiefs v. Revel, 25 USPQ2d 1601, 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016.
One cannot describe what one has not conceived. See Fiddles v. Baird, 30 USPQ2d 1481, 1483. In Fiddles v. Baird, claims directed to mammalian FGF's were found unpatentable due to lack of written description for the broad class. The Court further elaborated that generic statements are not adequate written description of the genus because it does not distinguish the claimed genus from others, except by function.
Mere idea or function is insufficient for written description; isolation and characterization at a minimum are required. A description of what a material does, rather than what it is, usually does not suffice. Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
Applicants do not identify the shared structural properties that would define the genus beyond the desired functionality. Currently the essential property of binding BCMA is imparted by the single, specific set of the 13 “variable X” amino acids in the DDpp scaffold sequences disclosed in the ~300 embodiments of the specifications. Specifically, the physical features (or amino acid residues encoding said features) which impart the property of a D-domain polypeptide binding BCMA should be disclosed. This lack of definition complicates the determination of the boundaries of the claimed genus with regard to which, as of yet unidentified, species variants (anti-BCMA D-domain polypeptides) would be anticipated, a priori, by one skilled in the art, to fall within the scope of the claims. Without the identification of the necessary shared structural properties of all species variants that fall within the scope of the genus, it may be that the ~300 species of anti-BCMA DDpp represent only a fraction of the library of 1016 DDpp of Lafleur, that bind BCMA, or only a fraction of the possible 1320 various possible embodiments of DDpp, based on the scaffold(s) of Lafleur, that bind BCMA. Based on this lack of description, it is left to the artisan to generate and screen candidate DDpps for BCMA binding activity in order to identify whether any given DDpp falls within the scope of the claimed genus, as no structure-to-function relationship is described.
In view of the lack of structure-to-function relationship, the enormous breadth of candidate D-domain polypeptides encompassed across various libraries, and the lack of a representative number of examples of the claimed genus, claim 1 is rejected for lack of adequate written description support. Claims 2-18 are also rejected as they are dependent on rejected claim 1 but fail to rectify the lack of descriptive support.
Claim Rejections – Maintained
Double Patenting
Claims 1-2 and 15-18 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 72-89 of copending Application No. 18/469,948 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the scope of the claims of application ‘948 anticipate that of the instant claims.
Application ‘948 claims a method of treating lymphoma or myeloma comprising administering a CAR which comprises an anti-BCMA DD (claims 72-74); wherein the lymphoma or myeloma comprise cells expressing BCMA (claim 75-76), wherein the myeloma is multiple myeloma (claims 77-78); whereby the CAR is expressed in immune effector cells (claims 79-80), or T cells (claims 81-82); are formulated for IV administration (claims 83-84); and are administered (claims 85-88). App ‘948 also claims a CAR comprising a BCMA DD (claim 89).
Thus, the CAR of app ‘948 claim 89, and the methods of treating of claims 72-88, anticipate the composition comprising the BCMA DD CAR of instant claims 1-2 and the methods of instant claims 15-18.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-11 and 15-18 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 72-89 of copending Application No. 18/469,948 in view of Lafleur (from IDS, Cite No. 16; WO 2016/164369; published 3/10/2016).
The reasons why claims 1-2 and 15-18 are rejected over app ‘948 are described above. However, app ‘948 does not claim the embodiments of the CAR with the specific limitations of the transmembrane and intracellular domains of instant claims 3-11.
Lafleur teaches anti-BCMA DD polypeptides as the extracellular antigen binding domain of a CAR, as described above. Lafleur teaches the CAR may comprise a CD8 transmembrane domain, an intracellular signaling domain of a human T cell receptor zeta domain or of 4-1BB, and a co-stimulatory intracellular domain of, for example, CD27 or CD28. Lafleur also teaches the anti-BCMA DD polypeptides may be fusion proteins, wherein the anti-BCMA DD polypeptide is fused to a serum protein polypeptide, as described above.
It would have been obvious to one of skill in the art to select specific embodiments of the transmembrane domain, intracellular signaling domain and co-stimulatory domain of a CAR from the art recognized alternatives for each component. One would be motivated to do so to optimize the CAR for therapeutic purposes. There would have been a reasonable expectation for success given that an anti-BCMA DD CAR may comprise a CD8 transmembrane domain, a CD3 zeta or 4-1BB intracellular signaling domain, and a CD27 intracellular co-stimulatory molecule, as taught by Lafleur et al. Thus, the invention was prima facie obvious to one of skill in the art at the time the invention was made.
Specifically, the anti-BCMA CAR of app ‘948 claims 72-89, in view of the various alternative embodiments of the transmembrane and intracellular signaling domains of the CAR of Lafleur, make obvious instant claims 3-11.
This is a provisional nonstatutory double patenting rejection.
Claims 1-18 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 72-89 of copending Application No. 18/469,948 in view of Lafleur (from IDS, Cite No. 16; WO 2016/164369; published 3/10/2016) and Nielsen et al., (US 2011/0293579; published 12/1/2011).
The reasons why claims 1-11 and 15-18 are rejected over app ‘948 and Lafleur are described above. However, app ‘948 and Lafleur do not teach wherein the anti-BCMA DD protein further comprises an AFP p26 polypeptide.
Lafleur also teaches the anti-BCMA DD polypeptides may be fusion proteins, wherein the anti-BCMA DD polypeptide is fused to a serum protein polypeptide, as described above.
Nielsen et al. teaches bispecific fusion proteins which may comprise a half-life modulator, which may comprise the serum protein AFP, or consist of a fragment of the AFP of instant SEQ ID NO: 969, as described above.
It would have been obvious to one of skill in the art to modify the anti-BCMA CAR of the methods of application ‘948 to comprise an anti-BCMA DD fusion protein comprising the AFP p26 fragment of instant SEQ ID NO: 969. One would have been motivated to do so given the knowledge that inclusion of an AFP p26 polypeptide increases half-life of the protein, as taught by Nielsen et al. There would have been a reasonable expectation for success given that the AFP polypeptide can be joined to a targeting polypeptide by a peptide bond, as taught by Nielsen et al.; and that the BCMA DBDpp can be a fusion protein whereby the BCMA DBDpp is fused, with or without a linker, to a serum polypeptide of interest, as taught by Lafleur et al. Thus, the invention was prima facie obvious to one of skill in the art at the time the invention was made.
Specifically, the anti-BCMA DD CAR of app ‘948 claims 72-89 in view of Lafleur and Nielsen, make obvious the anti-BCMA/AFP p26 protein of instant claims 12-14.
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
Applicant's arguments filed 2/3/2026 have been fully considered but they are not persuasive. Applicants contend that, as set forth in the MPEP, if a provisional nonstatutory double patenting rejection is the only rejection remaining in an application having the earlier patent term filing date, the examiner should withdraw the rejection in the application having the earlier patent term filing date and permit that application to issue as a patent. Further, applicants contend that the present application 1) has an earlier patent term filing date than application 18/469,948, and that 2) the instant application is otherwise in a condition for allowance (remarks, pg. 9, paras. 2-3; pg. 10, paras. 1-2).
In response the examiner acknowledges the MPEP in that, if an application is otherwise in condition for allowance, and the only remaining rejection is a provisional nonstatuatory double patenting rejection over a later filed application, the rejection for nonstatuatory double patenting will be withdrawn and the patent allowed to issue. However, in the instant application, the provisional rejection over nonstatuatory double patenting rejection is not the only rejection remaining. Thus, the arguments have not overcome the grounds for the rejection of claims 1-18 over application 18/469,948, in view of Lafleur and Nielsen, and the rejections are maintained.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JAMES R. MELCHIOR whose telephone number is (703)756-4761. The examiner can normally be reached M-F 8:00-5:00 CST.
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/JAMES RYLAND MELCHIOR/Examiner, Art Unit 1644
/NELSON B MOSELEY II/Primary Examiner, Art Unit 1642