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, in the reply filed on 3 August 2026 is acknowledged. The traversal is on the ground(s) that examining the method with the composition would not pose an undue burden since all methods required the claimed composition. This is not found persuasive because the instant application is a 371 application which is examined under unity of invention requirements. There is no requirement for search burden under unity of invention. As described in the Restriction/Election requirement dated 18 June 2026, unity of invention is fulfilled only when there is a technical relationship among the inventions involving one or more of the same or corresponding special technical features, (37 CFR 1.475(a)). As described in the requirement, the claims do not have unity of invention because the shared technical feature is not a special technical feature in view of Duan et. al. “The BCMA-targeted fourth-generation CAR-T cells secreting IL-7 and CCL19 for therapy of refractory/recurrent multiple myeloma.” Frontiers in immunology 12 (2021): 609421 published 4 March 2021, which teaches an anti-BCMA CAR-T for raising an immune response against multiple myeloma.
The requirement is still deemed proper and is therefore made FINAL.
The Examiner notes that, as described in the Restriction/Election requirement, should the product/apparatus claims be found allowable, withdrawn process claims that include all of the limitations of the allowable product/apparatus would be considered for rejoinder (Restriction/Election requirement 6/18/2026 p. 4-5).
Claims 10-52 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 3 August 2026.
Claim Status
Claims 1-52 are pending. Claims 10-52 are withdrawn as described in the Election/Restriction section above. Claims 1-9 are under examination in the instant office action.
Drawings
The drawings are objected to because the figure legend shown in Fig. 3 is not legible. 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.
Specification
The disclosure is objected to because of the following informalities: para. [0096] appears to inadvertently recite "The germ" rather than "The term".
Appropriate correction is required.
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-9 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.
Scope of the claimed genus
The instant claims are directed at a genus of compositions comprising “multiple myeloma-specific-CAR+ T cells”. The instant specification does not have a limiting definition but describes that “[t]he multiple myeloma-specific-CAR can include an extracellular ligand binding domain that binds to BCMA, GPRC5D, or other multiple myeloma-specific antigens” [00110]. No examples of other MM specific antigens are given.
Regarding claims 2 and 3, the claim limits the target antigen to BCMA and GPRC5D, respectively. No other structure is given to the CAR. Claim 4 is dependent on claim 2 but does not further limit the structure of the CAR.
Regarding claims 5-9, the claims are ultimately dependent of claim 1 without further limiting the structure of the composition comprising the multiple myeloma-specific-CAR+ cells, but rather recite intended use and results modifying the intended use that are directed at inherent characteristics of the composition.
State of the Relevant Art
Regarding chimeric antigen receptors and CAR-T cells, although there is a general structure known for a CAR, none of the elements of a traditional CAR are definitionally required for the structure of a chimeric antigen receptor. For example Zhang C, Liu J, Zhong JF, Zhang X. Engineering CAR-T cells. Biomark Res. 2017 Jun 24;5:22. doi: 10.1186/s40364-017-0102-y. PMID: 28652918; PMCID: PMC5482931, published 24 June 2017 teaches that CAR-T cells generally comprise an extracellular antigen-binding domain comprising an scFv, a spacer, a transmembrane domain, and an intracytoplasmic domain (See Figure 1). Zhang et. al. teaches that the engineering of CARs has evolved to include costimulatory modules such as CD137 (Fig. 2). Accordingly, second generation CARs added intracellular signaling domains from various co-stimulatory protein receptors to the cytoplasmic tail of the CARs to provide additional signals to the T cell, such as CD28 or CD137(4-1BB and CD134(OX40)), which can improve the proliferation, cytotoxicity, and sustained response, and prolong the life of CAR-T cells in vivo [16,17,18]” (See “Second generation” section).
Additionally, the genus of polypeptides encompassed by “chimeric antigen receptor” is much broader than the proto-typical CAR describe by Zhang et. al. For example, Zhao, Juanjuan, et al. "Universal CARs, universal T cells, and universal CAR T cells." Journal of hematology & oncology 11.1 (2018): 132 teach a biotin-binding immune receptor (BBIR) CAR wherein the extracellular binding domain is avidin, and therefore the target antigen can be swapped by switching for different biotinylated antigen specific molecules (Fig. 2); thus, the CAR polypeptide need not even comprise an extracellular targeting domain. Wang, Ying, et al. "Targeting FLT3 in acute myeloid leukemia using ligand-based chimeric antigen receptor-engineered T cells." Journal of hematology & oncology 11.1 (2018): 60 teach a CAR wherein the antigen-binding domain is FLT3 ligand (Fig. 1). Regarding intracellular signaling domains, although Zhang et. al. teach the “traditional” CD3z-containing intracellular signaling domain that activates T-cells, other domains are known in the art. For example, although not prior art, Pham-Danis, Catherine, et al. "Restoration of LAT activity improves CAR T cell sensitivity and persistence in response to antigen-low acute lymphoblastic leukemia." Cancer Cell 43.3 (2025): 482-502 teaches a CAR “ALA-CART” wherein the traditional costimulatory domain/CD3z combination is replaced by the intracellular signaling domain of the T-cell activation molecule linker for activation of T-cells (LAT). Additional, CARs with inhibitory signaling domains such as the intracellular domain of PD-1 are known in the art (Fedorov, Victor et. al. "PD-1–and CTLA-4–based inhibitory chimeric antigen receptors (iCARs) divert off-target immunotherapy responses." Science translational medicine 5.215 (2013): 215ra172-215ra172). It is unclear what effect a multiple-myeloma specific extracellular domain would have on these alternate types of intracellular signaling domains.
No one domain of a CAR has been shown to be purely structural or completely interchangeable. For example, Mazinani M et al. CAR-T cell potency: from structural elements to vector backbone components. (Biomarker Research 2022 10, Article number: 70 1-24) teaches the content and length of the hinge domain (equivalent to extracellular spacer) strongly influences the structural and functional properties of CAR including antitumor activity and side effects (page 6, left column, ¶2). Mazinani teaches that typical hinge include portions of the constant region of immunoglobulin molecules or non-Ig based hinges derived from the components naturally expressed on T cells. Mazinani teaches that effective antigen recognition is dependent on the length of the hinge and the target epitope distance from the cell membrane and therefore “HD length in CARs needs to be carefully tailored regarding the target epitope distance from the cell membrane to achieve improved antitumor efficacy (p. 6 left column ¶2- right column ¶1). Mazinani et. al. also teaches that IgG-derived spacers have ligand binding capacity that can determine persistence of CAR-T cells (p. 6 right column). Lastly, Mazinani et. al. teaches that the hinge can affect the immune response to the CAR in vitro and in vivo such as the degree of cytokine release syndrome. For example, compared with those containing hinges of CD8ɑ, those with CD28 HD/TMD produced significantly higher inflammatory cytokines and underwent more AICD (p. 7 left column ¶2-3). Thus, it would not have been predictable a priori what the structure and function of any undefined multipe-myeloma specific CAR would be.
Regarding compositions for CAR-T cell therapy of multiple myeloma, Grywalska, Ewelina, et al. "Paving the way toward successful multiple myeloma treatment: chimeric antigen receptor T-cell therapy." Cells 9.4 (2020): 983 teaches that multiple antigen targets are being studied in clinical trials with MM patients and that some of these results are published such as for BCMA, CD19, CD138, NKG2D, and kappa light chain antigens. Grywalska further teaches that trials of CAR T against additional antigens such as CD38, SLAMF7, CD44v6, CD56, GPRC5D, TACI, and NY-ESO-1. Still others are in preclinical stages such as CD229 and integrin beta-7 (Introduction ¶5, entire document). Grywalska et. al. teaches that “The working principle of CAR T cells is based on the binding reaction between the CAR and its targeted antigens, which induces the release of cytokines and cytotoxic granules, leading to the destruction of cancer cells (Figure 1B)” (Structure and Mechanism of Action of CAR T Cells, ¶1).
Grywalska et. al. teaches “Because of the difficulties in identifying a targeted antigen specific only to myeloma cells, scientists have focused their attention on non-cancer-specific antigens that become cancer-specific after post-translational modification, such as glycosylation” (Preclinical Studies: Integrin β7, and CD1d as Future Targets).
Grywalska et. al. teaches that there are additional concerns for CAR T cells and that scientists are still developing solutions for multiple myeloma directed T cells: “Another huge concern is the adverse effects that occur from the presence of target antigen on normal cells, called the “on-target/off-tumor” effect. For instance, CD38 is present on many cells, such as plasma cells, NK cells, monocytes, T cells, and B cells, and as a result CAR T cells targeting this antigen may induce cytopenia. This indicates the strong need for CAR T cells targeting only those antigens that are present on tumor cells” (Limitations and Future Development Strategies for CAR T Cells in MM Treatment” section ¶5). Grywalska teaches that antigen escape and expression of BCMA is another problem and that one solution is to “expand the palette of available antigens that can be targeted together with BCMA” (Limitations and Future Development Strategies for CAR T Cells in MM Treatment” section ¶7).
Even when the claims are limited to being specific for BCMA and specific for GPCR5D (and presuming a traditional scFv binding domain, which is not required by the instant claims), it is well established in the art that the formation of an intact antigen-binding site in an antibody usually requires the association of the complete heavy and light chain variable regions of a given antibody, each of which comprises three CDRs (or hypervariable regions) which provide the majority of the contact residues for the binding of the antibody to its target epitope. E.g., Almagro et. al., Front. Immunol. 2018; 8:1751 (see Section “The IgG Molecule” in paragraph 1 and Figure 1). While affinity maturation techniques can result in differences in the CDRs of the antibody compared to its parental antibody (page 3 “The IgG Molecule, second and third paragraphs), those techniques involve trial-and-error testing and the changes that maintain or improve affinity are not predictable a priori. E.g., id., (page 6 ending paragraph onto page 7). Chiu ML et al. (Antibodies 2019 8, 55, 1-80) teaches the antigen binding of antibodies often results in conformational changes in the contact surface areas of both the antibody and the antigen (page 5, first paragraph). Thus, the prediction of CDR binding to the epitope is difficult to predict. Chiu further teaches antibody modeling has been shown to be accurate for the framework region sequences, but CDR modeling requires further development and improvements (page 6, second paragraph). Prediction of the structure of HCDR3 could not be accurately produced when given the Fv structures without their CDR-H3s (page 6, second paragraph). Chiu teaches the quality of antibody structure prediction, particularly regarding CDR-H3, remains inadequate, and the results of antibody–antigen docking are also disappointing (page 11, paragraph 2). Sela-Culang et. al. "The structural basis of antibody-antigen recognition." Frontiers in immunology 4 (2013): 302 teaches contacting residues are more common at CDRs residues which are located at the center of the Ag combining site, and that non-contacting residues within the CDRs correspond with residues that are important for maintaining the structural conformations of the hypervariable loops and not necessarily for recognition of the Ag. Thus, without mutating the individual epitope interacting amino acids and the surrounding amino acids within the CDR and testing the binding, it is unknown how any give multiple myeloma-specific epitope will interact with the CDRs of an antigen binding domain.
The unpredictability of the antigen binding domain and the CAR backbone in a CAR with a complete undisclosed structure leads to unpredictability in the behavior of the CAR-T cells. For example, Sheykhhasan, Mohsen, et al. "CAR T therapies in multiple myeloma: unleashing the future." Cancer gene therapy 31.5 (2024): 667-686 teaches that publications after the instant effective filing date (6/28/2021) show that the therapy bb21217 was developed using the same anti-BCMA scFv, 4-1BB costimulatory motif, and CD3-zeta T cell activation domain found in previously tested therapy bb2121: “However, it also includes the phosphoinositide 3 kinase inhibitor bb007 during its ex vivo culture process” and that “This next-generation CAR T-cell therapy has shown promise in early clinical trials”. Thus, the instant claims encompass anti-BCMA CAR-T compositions that had yet to be invented as of the instant filing date. Sheykhhasan also states “Multiple Myeloma (MM) presents a significant challenge in oncology due to its complex tumor antigen heterogeneity, a critical aspect of the disease’s pathology” (Challenges of CAR T-cell therapy for MM, ¶1) and that “one challenge lies in finding more effective targets for CAR T-cell therapy and identifying suitable combination therapies” (Conclusion and future perspectives, ¶2). The instant claims read on any and all of these not-yet-identified combination therapies with unknown CARs and unknown additional components to the composition, and therefore a person of ordinary skill in the art would not understand Applicant to be in possession of the entire genus.
Summary of Species disclosed in the original specification
The instant specification discloses generation of CAR T cells by “transducing these cells with a lentiviral vector encoding a second generation CAR having a anti-MM-specific single chain variable fragment antibody, such [sic] anti-BMCA, a CD137 (4-1BB) or CD38 costimulatory motif, and a CD3-zeta signaling domain (Example 10). There are no working examples of structures of anti-multiple myeloma CAR T cells in the specification.
Summary
A genus of species is not present in the instant specification or prior art that would demonstrate a structure/activity relationship would be known for all anti-multiple myeloma CAR+ T cells. There is a lack of an appropriate number of species with any disclosed structure of the binding domain of the CAR, or with any structural limitations on the CAR whatsoever. There are only two species of anti-MM antigen discloses: anti-BCMA and anti-GPCR5D. As described in the state of the art section above, it was not predictable a priori which antigens would lead to specific anti-MM binding activity and which antigen binding domains would have efficacy and specific binding even once a particular antigen was identified. One of skill in the art would reasonably conclude that the applicant was not in possession of the genus of compositions comprising anti-multiple myeloma, anti-BCMA, and anti-GPCR5D CAR+ T cells as claimed. Dependent claims are rejected for failing to resolve the written description as described.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 3 and 4 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 3 is indefinite for the recitation of “GDRC5D-specific CAR+ T cells”. The gene “GDRC5D” does not appear to exist in the literature and is not mentioned in the specification. For the purposes of expedited prosecution, the claim will be interpretated as referring to “GPRC5D-specific CAR+ T cells” as described in the specification (e.g. [0096]).
Claim 4 is indefinite for the recitation of “wherein said composition is allogeneic”. First, allogeneic is a term that refers to the genetic material of both a subject and a cell; the composition comprises CAR-T cells which would have genetic material, but it is unclear whether the requirement that the composition is allogeneic reads specifically on the recited CAR T cells. Second, allogeneic is a term that assesses the genetic material of a cell relative to a subject. A CAR T cell cannot be ascertained to be autologous or allogeneic until it is administered to a particular subject. Thus, the metes and bounds of the claim would not be clear for the composition ex vivo, because ascertaining whether the CAR-T cell in the composition is allogeneic would require either administration to a subject or would be an intended use of the composition. For example, if the CAR-T cell in the composition is isolated and expanded from healthy donor PBMCs, but is only ever used for in vitro assays, a person of ordinary skill in the art could not be certain if it met the limitations of the instantly claimed composition.
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.
Claim(s) 1-2, 5-7, and 9 is/are rejected under 35 U.S.C. 102(a)(1) as being clearly anticipated by Li, Chunrui, et al. "Anti-BCMA CAR T-Cell Therapy in Relapsed or Refractory Multiple Myeloma with Extramedullary Disease and Plasma Cell Leukemia." (2019).
Claim interpretation: Regarding claim 1, the claim recites “A composition for use in raising an immune response to a plasma cell disorder”. The limitation of “for use” is an intended result that does not limit the claimed composition because the intended use does not add structure to the composition, but is rather and intended use and inherent property of the claimed composition (See MPEP §2111.02).
Regarding claims 1, 2, and 9 Li et. al. teaches a composition administered to multiple myeloma patients (reads on human subjects) comprising CAR-BCMA T cells that were 46.4% CAR positive (e.g. p. 9 “Patient characteristics” section; reads on multiple-myeloma specific CAR+ T cells and BCMA-specific CAR+ T cells). Regarding claim 9, the examiner notes that “wherein the subject is a human” modifies the “for use” preamble as described above but does not clearly limit the structure of the claimed composition and therefore is an intended property of the composition. Nevertheless, Li et. al. explicitly teaches that the composition is administered to human subjects and therefore evidences that the composition inherently possesses the claimed intended use property.
Regarding claim 5-6, the claim recites an intended result “wherein said composition induces an immune response in the subject when administered to said subject” that does not limit the claimed composition because it does not add structure to the composition as described for the “for use” limitation in claim 1 above. First, a CAR functions by inducing an immune response to antigen that leads to cytotoxicity against the tumor and therefore the instant anti-BCMA composition would inherently induce an immune response in the subject when administered to said subject. Second, Li et. al. evidence that inducing an immune response is an inherent property of the BCMA CAR because 1) patients responded to the therapy and achieved an objective response rate (ORR) of 90% and a complete response rate of 43.3% (claim 6), indicating that an immune response against the tumor was induced (e.g. p. 2 “Findings” section). Additionally, cytokine release syndrome (reads on inducing an immune response) was documented in 29 of the patients (e.g. p. 10 ¶2).
Regarding claim 8, the claim recites “wherein said complete remission is determined as a non-detectable M-spike and a negative immunofixation electrophoresis”. This is directed towards an intended use of the composition because claim 6 refers to the subject in the intended use of the preamble in claim 1. Regardless, Li et. al. teaches that M-protein was measured to assess response (p. 12). Therefore, the anti-BCMA CAR composition of Li et. al. that teaches all of the structural limitations of the composition reads on instant claim 7.
Regarding claim 7, the recitation of “wherein the composition prolongs progression free survival in said subject” is related to the intended use of claim 1 as described above and does not modify the structure of the composition. However, this is an inherent property of the composition of Li et. al. because Li et. al. teaches that progression-free survival of the heavily pre-treated population was 158 days which was superior to other salvage therapy (Abstract, p. 12-14).
Claim(s) 1-2, 4-9 is/are rejected under 35 U.S.C. 102(a)(1) as being clearly anticipated by NCT04093596 “Safety and Efficacy of ALLO-715 BCMA Allogenic CAR T Cells in in Adults With Relapsed or RefractoryMultiple Myeloma” (hereinafter NCT’596) published 16 September 2019 as evidenced by Mailankody S, et. al. Allogeneic BCMA-targeting CAR T cells in relapsed/refractory multiple myeloma: phase 1 UNIVERSAL trial interim results. Nat Med. 2023 Feb;29(2):422-429. doi: 10.1038/s41591-022-02182-7. Epub 2023 Jan 23. Erratum in: Nat Med. 2023 Dec;29(12):3271. doi: 10.1038/s41591-023-02306-7. PMID: 36690811 and Kumar, S. et al. International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma. Lancet Oncol. 17, e328–e346 (2016).
Claim interpretation: Regarding claim 1, the claim recites “A composition for use in raising an immune response to a plasma cell disorder”. The limitation of “for use” is an intended result that does not limit the claimed composition because the intended use does not add structure to the composition, but is rather and intended use and inherent property of the claimed composition (See MPEP §2111.02).
Regarding claims 1, 2, and 4, NCT’596 teaches a composition comprising an allogeneic anti-BCMA CAR-T cell for relapsed or refractory multiple myeloma (See “Arms and Interventions”; reads on multiple myeloma specific and BCMA specific).
Regarding claims 5-6, the claim recites an intended result “wherein said composition induces an immune response in the subject when administered to said subject” that does not limit the claimed composition because it does not add structure to the composition as described for the “for use” limitation in claim 1 above. First, a CAR functions by inducing an immune response to antigen that leads to cytotoxicity against the tumor and therefore the instant anti-BCMA composition would inherently induce an immune response in the subject when administered to said subject. Second, as evidenced by Mailankody et. al., it is an inherent property of the allogeneic anti-BCMA CAR-T cell that they induced an immune response because the patients administered the allo-BCMA-CAR-T had a 55.8% response rate with 25% having a complete or stringent complete response and cytokine release syndrome also occurred in 55.8% of patients (reads on induces an immune response).
Regarding claim 8, the limitation “wherein said complete remission is determined as a non-detectable M-spike and negative immunofixation electrophoresis” is not required by the claim because it does not further limit the structure of the composition but recites and intended use and inherent property of the composition as described for claim 1 above. As evidenced by Mailankody et. al. and Kumar et. al., Mailankody et. al. teaches that clinical response and disease progression were assessed by the investigator according to the international Myeloma Working Group consensus criteria (See “Endpoints and study procedures” ¶2) and Kumar et. al. teaches that the International Myeloma Working Group consensus criteria classifies a complete response as “negative immunofixation on the serum and urine” wherein the immunofixation is used to detect M protein (synonymous for M spike) (e.g. Table 4).
Regarding claim 7, the recitation of “wherein the composition prolongs progression free survival in said subject” is related to the intended use of claim 1 as described above and does not modify the structure of the composition. As evidenced by Mailankody et. al. and Kumar et. al. “the relationship between complete response and progression-free survival, or time-to-progression, has been more consistent than the relationship between complete response and overall survival (“Depth of response and long-term outcome section”, ¶1). Therefore, it would be an inherent property of the composition of NCT’956 that is extends progression-free survival due to the correlation between the complete response taught by Mailankody et. al.
Regarding claim 9, the examiner notes that “wherein the subject is a human” modifies the “for use” preamble as described above but does not clearly limit the structure of the claimed composition and therefore is an intended property of the composition. Nevertheless NCT’596 as evidenced by Mailankody et. al. and Kumar et. al. teaches administration to multiple myeloma patients (reads on human subject).
Claim(s) 1, 3, and 5-7 are rejected under 35 U.S.C. 102(a)(1) as being clearly anticipated by Smith et al. ,GPRC5D is a target for the immunotherapy of multiple myeloma with rationally designed CAR T cells.Sci. Transl. Med. 11 , eaau7746 (2019). DOI:10.1126/scitranslmed.aau7746 published 27 March 2019.
Claim interpretation: Regarding claim 1, the claim recites “A composition for use in raising an immune response to a plasma cell disorder”. The limitation of “for use” is an intended result that does not limit the claimed composition because the intended use does not add structure to the composition, but is rather and intended use and inherent property of the claimed composition (See MPEP §2111.02).
Regarding claims 1 and 3, Smith et. al. teaches a composition comprising anti-GPCR5D CAR T cells for targeting multiple myeloma (see e.g. Abstract, entire document, Fig. 6) (reads on multiple-myeloma specific CAR T, GPCR5D specific CAR T).
Regarding claim 5-7, the claim recites an intended result “wherein said composition induces an immune response in the subject when administered to said subject” that does not limit the claimed composition because it does not add structure to the composition as described for the “for use” limitation in claim 1 above. First, a CAR functions by inducing an immune response to antigen that leads to cytotoxicity against the tumor and therefore the instant anti-GPCR5D composition would inherently induce an immune response in the subject when administered to said subject. Second, Smith et. al. teaches administration of the CAR-T cells lead to clearance of MM tumors in a xenograft model which would require induction of an immune response (by the administered CAR T cells) as described (Fig. 6). Regarding claim 6, Smith et. al. teaches that “At 100 days after CAR T cell injection, only mice treated with GPRC5D(109)-containing CAR T cells maintained 100% survival” and shows that the tumors are eradicated (Fig. 6C; reads on complete remission). Regarding claim 7, the recitation of “wherein the composition prolongs progression free survival in said subject” is related to the intended use of claim 1 as described above and does not modify the structure of the composition. Additionally, the instant specification does not define progression-free survival. Smith et. al. teaches that the GPRC5D mice had 100% survival at 100 days which was longer than Mock CAR-T and BCMA CAR-T (Fig. 6C-F).
Conclusion
No claims are allowed.
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/KATHLEEN CUNNINGCHEN/ Examiner, Art Unit 1646
/GREGORY S EMCH/ Supervisory Patent Examiner, Art Unit 1678
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