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 .
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 claims benefit under 35 U.S.C. 119(e) to U.S. Provisional applications 63/504184, filed 5/24/2023 and 63/497185, filed 4/19/2023.
Status of Claims
Claims 1, 3-4, 6, 17, 23, 26-27, 34, 37, 39-40, 62-64, 67, 78 and 87-89 are pending and are being examined on the merits.
Claim Objections
Claim 67 objected to because of the following informalities:
Claim 67 recites acronyms “DPd” and “PVd” without identifying what these stand for. If applicants are to use acronyms in the claims, the acronym should be defined on first use, and then used throughout the claims for consistency. Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
Claims 1, 3-4, 6, 17, 23, 26-27, 34, 37, 39-40, 62-64, 67, 78 and 87-89 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.
Each of claims 1, 3-4, 6, 17, 23, 26-27, 34, 37, 39-40, 62-64, 67, 78 and 87-89 recite optional limitations using the term “optionally”. The use of “optionally” in these instances renders the claims indefinite as it is unclear if the terms that follow, which further limit the preceding limitations, are part of the claimed invention or are exemplary embodiments. In some instances (for example, claim 17), the entire body of the claim is “optional” such that the claim does not further limit the invention in any way (see below). Therefore the metes and bounds of the claims are unclear.
For further examination, the limitations following the term “optionally”, in each claim, are considered to not be required, but rather to identify exemplary embodiments; whereby “optionally” is considered analogous to “such as” language. As the limitations following “optionally” are not considered to be required, said limitations do not inform as to the patentability of the claims over the prior art.
Claims 6, 63 and 88 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 6 recites the limitation "the high-risk feature" in line 2. There is insufficient antecedent basis for this limitation in the claim. Claim 6 depends from claim 1. However claim 1 does not require a “high-risk feature” (it is optional language), and therefore does not provide sufficient antecedent basis for further limiting the “high-risk feature” of claim 6.
Claim 63 recites the limitation "the neurotoxicity" in line 1. There is insufficient antecedent basis for this limitation in the claim. Claim 63 depends from claim 62, which depends from claim 40, which depends from claim 1. However, none of claims 1, 40 or 62 require a “neurotoxicity” (it is optional language), and therefore the claims do not provide sufficient antecedent basis for further limiting “the neurotoxicity” of claim 63.
Claim 88 recites the limitation "the neurotoxicity" in line 1. There is insufficient antecedent basis for this limitation in the claim. Claim 88 depends from claim 87, which depends from claim 67, which depends from claim 1. However, none of claims 1, 67 or 87 require a “neurotoxicity” (it is optional language), and therefore the claims do not provide sufficient antecedent basis for further limiting “the neurotoxicity” of claim 88.
Claims 40 and 62-64 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 40 recites the method of claim 1 wherein the anti-BCMA extracellular domain comprises a first and second anti-BCMA VHH, “wherein the first VHH domain comprising a CDR1, a CDR2 and a CDR3 as set forth in the VHH domain comprising the amino acid sequence of SEQ ID NO: 2.” This claim language is incoherent. It is unclear what the minimal requirements of the VHH sequence are. Are the VHHs limited to the sequences defining the CDRs, or are the VHHs limited to SEQ ID NOs: 2 and 4, whereby the VHHs must comprise any undefined CDR1, CDR2 and CDR3? No patentable weight is given to limitations after the term “optionally”, as described above. However, the claim also recites optional language regarding specific CDR sequences with defined SEQ ID NOs, as well as optional language for the full sequences of SEQ ID NOs: 2 and 4. In particular, the claim language recites “comprising a CDR1” of the VHH of SEQ ID NO: 2, which is unclear. For example, if the claims recited “comprises the CDR1” of SEQ ID NO: 2, then it is clear the claim is limited to “the CDR1”. However, “comprising a CDR1” results in confusion as to whether the VHH must comprise any CDRs 1-3, or whether the claim is limited to the CDRs 1-3 of the full VHH sequence. As the metes and bounds of the claim limitations are unclear, claim 40 is rejected for indefiniteness. As claims 62-64 depend from claim 40, yet fail to rectify the indefiniteness issues, claims 62-64 are also rejected.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 17 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim 17 recites the methods of claim 1, wherein the subject has received one, two or three prior lines of therapy, “wherein optionally”… . Claim 1 recites a method of treating a subject, wherein the subject has multiple myeloma, and has received one to three prior lines of therapies. Given that any text following the term “wherein optionally” is not required, and thus do not inform the patentability of the claims (as described above), claim 17 does not further limit the method of claim 1, from which it depends. Rather, claim 17 re-states the same limitations of claim 1, all of which are already incorporated into claim 17 on the basis of its dependency from claim 1.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1, 3-4, 6, 17, 23, 26-27, 34, 37 and 39 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Juno Therapeutics, henceforth Juno, (WO 2021/222330; published 11/4/2021).
Juno teaches BCMA-directed T cell therapies in combination with immunomodulatory compounds, and methods for treating subjects with diseases and conditions associated with BCMA (abstract). Juno teaches the T cell therapy includes cells that express recombinant receptors such as chimeric antigen receptors (CARs) directed against BCMA; and wherein the disease or condition is multiple myeloma for refractory multiple myeloma (pg. 1, para 0003).
Specifically, Juno teaches a method of treating multiple myeloma comprising administering a T cell therapy to a subject having relapsed or refractory multiple myeloma, said T cell therapy comprising a dose of genetically engineered T cells expressing a CAR that specifically binds to BCMA (pg. 224, claim 1). Juno teaches the CAR comprises an antigen binding domain that binds to BCMA, a transmembrane domain and an intracellular signaling region comprising a CD3-zeta chain (pg. 236, claim 82). Juno teaches the method of treating wherein the subject has relapsed or been refractory following at least 3 or at least 4 prior therapies for multiple myeloma; whereby the prior therapies include an immunomodulatory agent, a proteasome inhibitor or an anti-CD38 antibody therapy; wherein the immunomodulatory agent is lenalidomide, or wherein the proteasome inhibitor is bortezomib (pg. 227, claims 15-18). Juno also teaches wherein, at the time of administration, the subject has International Myeloma Working Group (IMWG) high risk cytogenetics (pg. 228, claim 21).
Regarding claim 1; Juno teaches a method of treating multiple myeloma comprising administering CAR-T cell therapy, wherein the CAR-T cells express an anti-BCMA CAR, which comprises a transmembrane domain and an intracellular signaling domain, wherein the subject has had three prior lines of therapy, including immunomodulatory drug (lenalidomide) therapy, which the subjects were refractory to. Thus, the methods, CAR-T cells and subjects of Juno anticipate instant claim 1.
Regarding claims 3-4, 6 and 17; Juno teaches the subjects, at the time of administration of the therapeutic method for treating multiple myeloma, have high risk cytogenetics. Thus, the methods of Juno anticipate a method comprising a step of determining whether the subject has high risk cytogenetics, of claim 3, or whereby the subject has been determined to have high risk cytogenetics, of claim 4. Similarly, as Juno teaches wherein the subjects have high risk cytogenetics, Juno anticipates instant claim 6. As Juno teaches the subjects have received 3 prior therapies, Juno anticipates instant claim 17.
Regarding claim 23; Juno teaches the subjects received, and has relapsed or been refractory to (pg. 5, para. 0014), an immunomodulatory agent which may be pomalidomide (pg. 227, claim 17), or a proteasome inhibitor treatment, which includes bortezomib (claim 18). As “relapsed” encompasses that the patient had an outcome of stable, or minimal response, before relapsing or becoming refractory to the prior treatment, the prior treatments of Juno encompass a bridging therapy. Further, Juno teaches wherein the method comprises the subject receiving a lymphodepleting therapy (pg. 186, claim 80). Thus, the methods and subjects of Juno anticipate instant claim 23.
Regarding claim 26; Juno teaches the cell therapy comprises administration of a dose comprising a number of cells that is 0.5 x 106, or 1 x 106, cells/kg (pg. 51, para. 0186). Thus, Juno anticipates instant claim 26.
Regarding claim 27; Juno teaches administration of anti-BCMA CAR T cells reduced tumor burden and improved survival in mouse models of multiple myeloma (pg. 196, para. 0620; Fig. 6). Thus, Juno teaches the methods were effective in obtaining an overall response in the subject, and anticipates instant claim 27. As “overall response” is not specifically defined, such as by using the overall response rate (ORR) terminology and criteria (which is not made “optional”), the phrase “overall response” is given its broadest reasonable interpretation, and includes, for example, increased survival rate.
Regarding claims 34 and 37; Juno teaches the subject is monitored for toxicity or other adverse outcomes, including treatment related outcomes, such as cytokine release syndrome (CRS) or neurotoxicity, in subjects administered the provided the cell therapy (pg. 157, para. 0515). Further, Juno teaches CRS can occur following adoptive T cell therapy (pg. 158, para. 0518); and may be treated using anti-inflammatory therapy such as anti-IL-6 antibody, such as tocilizumab (pg. 159, para. 0519). Thus, Juno teaches treating the subject for an adverse event, namely CRS, with administration of tocilizumab. As such, the methods of Juno anticipate instant claim 34; and wherein the treating the CAR-T associated AE occurs after administering the T cells, of instant claim 37.
Regarding claim 39; Juno teaches that CD3+ cells comprising the CAR remained detectable at day 14 (pg. 197, para. 0621; Fig. 6C). Thus, Juno anticipates instant claim 39.
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 40 and 62-64 are rejected under 35 U.S.C. 103 as being unpatentable over Juno, (WO 2021/222330; published 11/4/2021) and Fan et al., (WO 2018028647; published 2/15/2018), as evidenced by Chng et al., (Leukemia, 2014, 28:269-277).
The reasons why Juno anticipates the methods of claims 1, 3-4, 6, 17, 23, 26-27, 34, 37 and 39 are described above. However, Juno does not teach wherein the anti-BCMA extracellular binding domain of the CAR comprises a first and second anti-BCMA VHH domain, wherein the first and second VHH domains comprise the sequence of instant SEQ ID NOs: 2 and 4, respectively.
Fan et al. teaches chimeric antigen receptors (CAR) targeting BCMA, wherein the CARs are multivalent, comprising one or more anti-BCMA single-domain antibodies, as well as engineered immune effector cells, such as T cells, comprising the CARs and methods of treating cancer (abstract).
Structurally, Fan teaches an exemplary multivalent BCMA CAR may be that of GSI5021, defined by SEQ ID NO: 300 (pg. 95-96, Table 5; pg. 9, para. 0024). Fan SEQ ID NO: 300 is 100% identical in amino acid sequence to instant SEQ ID NO: 17, of claim 40. It comprises a first anti-BCMA binding moiety of instant SEQ ID NO: 2 and a second anti-BCMA binding moiety of instant SEQ ID NO: 4 with 100% sequence identity for each. It comprises the linker of instant SEQ ID NO: 3, the signal peptide of instant SEQ ID NO: 1, the transmembrane domain of instant SEQ ID NO: 6, the intracellular signaling domain of instant SEQ ID NO: 8 and the hinge domain of instant SEQ ID NO: 5 (of instant claim 40), all with 100% sequence identity. Thus, the GSI15021 embodiment of the multivariant anti-BCMA CAR of Fan SEQ ID NO: 300 is identical to the exemplary embodiment of the anti-BCMA CAR of instant SEQ ID NO: 17.
Note that the instant specifications define instant SEQ ID NO: 17 as encoding the Ciltacabtagene autoleucel (Cilta-cel) CAR (see specs., pg. 146). Thus, Fan, SEQ ID NO: 300, teaches the “Cilta-cel” anti-BCMA CAR known in the art.
Fan teaches the CAR of SEQ ID NO: 300 (i.e. Cilta-cel) may be used in generating engineered immune cells, including T cells, wherein the CAR comprises a first and a second BCMA binding moiety, a transmembrane domain and an intracellular signaling domain (pg. 114, paras. 0334-0335; para. 0336, pg. 118, last line). Fan teaches a method of treating cancer, such as multiple myeloma, in a human individual, comprising administering an effective amount of a pharmaceutical composition comprising an engineered T cell comprising any of the disclosed multivalent CARs (pgs. 134-135, paras. 0391-0392; pg. 146, para. 0405; pg. 191, claims 35-43).
As such Fan discloses the multivalent anti-BCMA CAR of “Cilta-cel” to engineer T cells expressing the CAR, and to administer a composition of the engineered T cells in a method of treating an individual with multiple myeloma.
It would have been obvious to one of skill in the art to modify the methods of Juno, comprising administering an composition of CAR-T cells expressing an anti-BCMA CAR, to use the anti-BCMA CAR Cilta-cel, of Fan et al. One would have been motivated to do so as selecting an alternative species of anti-BCMA CAR might improve the therapeutic efficacy of the treatment of refractory multiple myeloma. There would have been a reasonable of success given that the CAR constructs of Juno and the CAR construct of Fan are alternative anti-BCMA constructs for use in an anti-BCMA CAR, which will target the CAR-T cells of the therapeutic methods to the same antigen, and thus are each being used for the same purpose as they were taught in the art.
Regarding claim 40, the combination of Juno and Fan makes obvious wherein the anti-BCMA extracellular binding domain of the CAR comprises the first and second VHH of instant SEQ ID NOs: 2 and 4, respectively, and wherein the anti-BCMA CAR-T cells are administered to the selected patient population, of Juno, in a method for treating refractory multiple myeloma. Thus, the combination of Juno and Fan make obvious instant claim 40.
Regarding claims 62-63. As Juno teaches the method further comprises treating the subject for an AE, specifically, treating CRS with tocilizumab (pg. 159, para. 0519), after administering the CAR-T cells; the combination of Juno and Fan make obvious instant claim 62. Similarly, Juno teaches AEs related to the outcome of cell therapy may include neurotoxicity (pg. 163, para. 0533), which may be a manifestation of severe CRS, and be treated with anti-IL-6 antibody and/or steroids. Thus, the combination of Juno and Fan make obvious instant claim 63.
Regarding claim 64; Juno teaches wherein the subject has IMWG high risk cytogenetics, as described above, (pg. 5, para. 0014; pg. 228, claim 21). While Juno is silent as to the parameters that define the high risk cytogenetics, Juno describes them as in accordance with IMWG. Chng et al., (Leukemia, 2014), describes the risk stratification in myeloma, on behalf of the International Myeloma Working Group (title, authors). Chng describes high risk cytogenetic parameters as including a 17p13 deletion and/or t(4;14) (pg. 272, Table 2; pg. 273, Table 3). Thus, Chng provides evidence that the “IMWG high risk cytogenetics” limitation of subjects, of Juno, encompasses a del(17p) or t(4;14) genetic mutation/abnormality, as these parameters define the “high risk” features of patients with multiple myeloma according to the IMWG. Thus, as Juno encompasses high risk cytogenetic subjects having a del(17p) or t(4;14) genetic abnormality, the combination of Juno and Fan make obvious instant claim 64.
Claims 67, 78, and 87-89 are rejected under 35 U.S.C. 103 as being unpatentable over Juno, (WO 2021/222330; published 11/4/2021) and Fan et al., (WO 2018028647; published 2/15/2018), as evidenced by San-Miguel et al., (N Engl J Med, 2023), and as evidenced by Chng et al., (Leukemia, 2014, 28:269-277).
As described above, Fan teaches the anti-BCMA CAR of SEQ ID NO: 300, which is 100% identical to instant SEQ ID NO: 17, which is the anti-BCMA CAR Ciltacabtagene autoleucel, or “Cilta-cel”. Thus, the combination of Juno and Fan make obvious a method of treating a subject with refractory multiple myeloma, wherein the subject has received 3 prior lines of therapy, and/or wherein the subject has a high-risk feature, and wherein the administered CAR-T cells express the anti-BCMA CAR of Cilta-cel.
Claim 67 recites the method of claim 1, wherein the administration of the CAR-T cells is effective in obtaining a greater “very good partial response” (VGPR), or a “very good partial response or better” response in the subject as compared to an administration of DPd or PVd treatment. DPd is a daratumumab-pomalidomide-dexamethasone treatment, and PVd is a pomalidomide-bortezomib-dexamethasone treatment.
The combination of Juno and Fan do not teach a specific comparison of the CAR-T cells with a DPd or PVd treatment, or it’s efficacy in obtaining a VGPR response measure.
However, San-Miguel et al., (2023, NEJM) teaches the results of CARTITUDE-4 clinical trial number NCT04181827 (abstract). San-Miguel teaches the clinical trial comprises treatment patients with refractory multiple myeloma with either cilta-cel anti-BCMA CAR-T cell therapy or standard care (abstract). San-Miguel teaches the standard care methods were DPd or PVd treatments (pg. 336, col. 2, para. 2). San-Miguel teaches the Cilta-cel treatment resulted in a “VGPR or better” of 81.2% as compared to Standard Care treatment, which was 45.5% (pg. 343, Table 2). Thus, San-Miguel provides evidence that Cilta-cel anti-BCMA CAR-T cell therapy is effective in obtaining a greater VGPR response as compared to DPd or PVd treatment.
Regarding claim 67; as the combination of Juno and Fan make obvious a treatment of multiple myeloma comprising administering Cilta-cel anti-BCMA CAR-T cell therapy, it is an inherent property of the Cilta-cel CAR-T cell therapy to obtain a greater VGPR response in subjects as compared to DPd or PVd treatment. Thus, the combination of Juno and Fan make obvious instant claim 67.
MPEP section 2112(I) discusses inherent properties, and states “the discovery of a previously unappreciated property of a prior art composition does not render the old composition patentably new to the discoverer; thus claiming a new or unknown property which is inherently present in the prior art does not make the claim patentable.” Further, the fact that a characteristic is a necessary feature or result of a prior-art embodiment is enough for inherent anticipation, even if the fact was unknown at the time of the prior invention (MPEP 2112(II). In the instant case, the anti-BCMA CAR-T cells of Fan, in the combination methods of Fan and Juno, are 100% identical to the Cilta-cel CAR-T cells of San-Miguel. Thus, San-Miguel provides post-filing evidence that the Cilta-cel anti-BCMA CAR-T cell methods of the combination of Juno and Fan was inherently capable of obtaining a greater VGPR response compared to DPd or PVd treatments. Thus the claimed properties of claim 67 do not provide a patentable point of novelty over combination of Fan and Juno, which discloses the identical Cilta-cel anti-BCMA CAR of San-Miguel, whereby Cilta-cel was previously disclosed in the art for use in methods of treating multiple myeloma, by Fan.
Regarding claim 78; Juno teaches wherein the IMiD is lenalidomide. Thus the combination of Juno and Fan make obvious instant claim 78.
Regarding claims 87-89; Juno teaches methods of treating AEs that may result from administering the CAR-T cells, which include CRS (claim 87) or neurotoxicity (claim 88), wherein the treatment comprises administering tocilizumab, or alternative anti-IL-6 antibodies, or steroids. Thus, the combination of Juno and Fan make obvious instant claims 87-88. Further, Juno teaches wherein the subjects have “IMWG high risk cytogenetics”, and Chng provides evidence that IMWG high risk cytogenetics encompasses a del(17p) or t(4;14) genetic abnormality, by definition. Thus, the combination of Juno and Fan make obvious instant claim 89, as evidenced by Chng.
Double Patenting
Statutory
A rejection based on double patenting of the “same invention” type finds its support in the language of 35 U.S.C. 101 which states that “whoever invents or discovers any new and useful process... may obtain a patent therefor...” (Emphasis added). Thus, the term “same invention,” in this context, means an invention drawn to identical subject matter. See Miller v. Eagle Mfg. Co., 151 U.S. 186 (1894); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Ockert, 245 F.2d 467, 114 USPQ 330 (CCPA 1957).
A statutory type (35 U.S.C. 101) double patenting rejection can be overcome by canceling or amending the claims that are directed to the same invention so they are no longer coextensive in scope. The filing of a terminal disclaimer cannot overcome a double patenting rejection based upon 35 U.S.C. 101.
Claims 1, 3-4, 6, 17, 23, 26-27, 34, 37, 39-40, 62-64, 67, 78 and 87-89 are provisionally rejected under 35 U.S.C. 101 as claiming the same invention as that of claim 1, 3-4, 6, 17, 23, 26-27, 34, 37, 39-40, 62-64, 67, 78 and 87-89 of copending Application No. 18/639,682 (reference application). This is a provisional statutory double patenting rejection since the claims directed to the same invention have not in fact been patented.
The claims of application 18/639682 are identical to that of the instant application.
Non-Statutory
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 17, 26 and 40 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-62 of U.S. Patent No. 12,522,645. Although the claims at issue are not identical, they are not patentably distinct from each other because the scope of the claims of US Patent ‘645 anticipate that of the instant claims.
US ‘645 claims a method of treating a subject who has cancer comprising administering a dose of cells comprising a CAR, wherein the CAR has a first BCMA binding moiety of SEQ ID NO: 1 and a second BCMA binding moiety of SEQ ID NO: 3, wherein the CAR has a transmembrane domain and a intracellular domain, wherein the cancer is refractory multiple myeloma, wherein the dose is 5 x 105 to 1 x 106 cells, wherein the cells are T cells, whereby the cells are administered as a single dose, and whereby the patient has received multiple lines of therapy comprising a proteasome inhibitor, and immunomodulatory agent and an anti-CD38 monoclonal antibody (claim 1). US ‘645 also claims wherein the anti-BCMA binding moieties have the nucleic acid sequence of SEQ ID NOs: 2 and 4 (claims 33-34); a linker of SEQ ID NO: 5 (claims 35-36), a signal peptide of SEQ ID NO: 6 (claims 37-40), a transmembrane domain of SEQ ID NO: 8 (claims 41-42), a primary intracellular signaling domain derived from CD3ζ (claims 43-44), a costimulatory signaling domain of SEQ ID NOs: 10 or 12 (claims 45-49), a hinge domain of SEQ ID NO: 15 (claims 50-52).
The BCMA binding domain of US ‘645 SEQ ID NOs: 1 and 3 are 100% identical to that of instant SEQ ID NOs: 2 and 4, respectively. The nucleic acid sequences of US ‘645 SEQ ID NOs: 2 and 4 are 100% identical that that of instant SEQ ID NOs: 10 and 12, respectively. The linker of US ‘645 SEQ ID NO: 5 is identical to that of instant SEQ ID NO: 3. The signal peptide of US ‘645 SEQ ID NO: 6 is identical to that of instant SEQ ID NO: 1. The transmembrane domain of US ‘645 SEQ ID NO: 8 is identical to that of instant SEQ ID NO: 6. The co-stimulatory signaling domains of US ‘645 SEQ ID NOs: 10 and 12 are identical to instant SEQ ID NOs: 8 and 7, respectively. The hinge domain of US ‘645 SEQ ID NO: 15 is identical to that of SEQ ID NO: 5. Further, all of the above components of the CAR are comprised in the single embodiment of the CAR of instant SEQ ID NO: 17.
US ‘645 also claims wherein the cells are expanded prior to infusion (claim 2), wherein the T cells are heterologous T cells (claim 3), wherein the dose is 5.5 x 105 to 8 x 105 kg/mass (claim 4), 7.5 x 105 (claim 5), 1 x 106 to 1 x 108 (claim 6), 2 x 107 to 8 x 108 (claim 7), 5.25 x 107 (claim 8), 5 x 105 to 1 x 106 (claim 9), 5.5 x 105 to 8 x 105 (claim 10), 7.5 x 105 (claim 11), 1 x 106 to 1 x 108 (claim 12), 2 x 107 to 8 x 107 (claim 13), 5.25 x 107 (claim 14). US ‘645 claims whereby the cells are administered IV (claim 15). US ‘645 claims whereby the T cells are a mix of CD4+ and CD8+ T cells with varying ratios (claims 16-30 and 56), or wherein the T cells expressing the CAR comprise a predominant phenotype in varying levels (claims 57-62). US ‘645 also claims wherein the first and/or second BCMA binding moiety is a sdAb (claims 31-32). US ‘645 claims wherein the T cells are autologous (claim 53), allogenic (claim 54), and whereby the subject is human (claim 55).
The structure of the CAR of US ‘645 anticipates the structure of the CAR the instant claims; and the methods of treating a cancer, or refractory multiple myeloma, comprising administering a composition of genetically engineered T cells expressing the CAR of US ‘645 are the same as the methods of the instant claims, including wherein the subject has at least 3 prior lines of treatment. Therefore, US ‘645 claims 1-62 anticipate instant claims 1, 17, 26 and 40.
Claims 1, 3-4, 6, 17, 23, 26-27, 34, 37, 39-40, 62-64, 67, 78 and 87-89 rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-62 of U.S. Patent No. 12,522,645 in view of Juno, (WO 2021/222330; published 11/4/2021), as evidenced by San-Miguel et al., (N Engl J Med, 2023), and as evidenced by Chng et al., (Leukemia, 2014, 28:269-277).
The reasons why claim 1, 17, 26 and 40 are anticipated by US ‘645 are described above. Specifically, US ‘645 claims the “Cilta-cel” anti-BCMA CAR-T cells and administering the cells in a method for treating refractory multiple myeloma, wherein the subjects have received one to three prior lines of therapy.
However, US ‘645 doesn’t teach extending the methods to subjects having a high-risk feature, and the various limitations pertaining to the parameters of the high risk feature, addressing various AEs, and obtaining expected responses and outcomes.
Juno makes obvious methods of treating subjects with refractory multiple myeloma with anti-BCMA CAR-T cell therapy, whereby the subjects have had multiple lines of prior treatment, and have high risk features. Thus, Juno makes obvious administering the Cilta-cel anti-BCMA CAR-T cell therapy to “selected” high risk subjects with refractory multiple myeloma, as described above. Thus the “selected” patient population does not provide any patentable point of novelty to the instant methods.
Chng et al. provides evidence that Juno’s reference to “IMWG high risk cytogenetics”, encompasses specific del(17p) or t(4;14) genetic abnormalities, and thus these specific parameters do not provide any patentable point of novelty to the instant methods, as described above.
San-Miguel et al. provides evidence that the “Cilta-cel” anti-BCMA CAR-T cell therapy provides greater response rates as compared to standard care DPd or PVd regimens. Thus, claims to the results “obtained”, or the “effective” properties of the “Cilta-cel” anti-BCMA CAR-T cell therapy are inherent properties of the identical product and methods, and do not provide any patentable point of novelty to the instant methods, as described above.
Thus, US ‘645, claims 1-62, which teach the identical “Cilta-cel” anti-BCMA CAR-T cell therapy, in view of applying the therapy to selected patients with high risk features, as described by Juno, and wherein the specific limitations of the features are evidenced by Chng et al. and/or San-Miguel et al., make obvious instant claims 1, 3-4, 6, 17, 23, 26-27, 34, 37, 39-40, 62-64, 67, 78 and 87-89, for the same reasons as described above.
Claims 1, 17, 23, 26, 34, 37 and 40 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4-6, 8, 12-24, 26-32, 35-39, 46 and 82-94 of copending Application No. 17/540,736 (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 ‘736 anticipate that of the instant claims.
Application ‘736 claims a method of treating a subject who has multiple myeloma comprising administering to the subject a dose of T cells comprising a CAR comprising the amino acid sequence of SEQ ID NO: 17, wherein the does comprises 0.5 x 106 to 1.0 x 106 cells/mass, wherein the method comprises administering the T cells no later than 3 hours following thawing of the T cells, wherein the subject has received prior treatment with at least three prior lines of treatment, and wherein the subject has received an anti-pyretic and an antihistamine up to about 1 hour prior to infusion of the dose of CAR-T cells (claim 1), or whereby the dose of CAR-T cells is administered via a single IV infusion (claim 85).
The CAR of application ‘736 SEQ ID NO: 17 is 100% identical to the CAR of instant SEQ ID NO: 17. Therefore the CAR of application ‘736 SEQ ID NO: 17 comprises the sdAb VHH domains of instant SEQ ID NOs: 2 and 4, or polypeptides encoded by the nucleic acid sequences of instant SEQ ID NOs: 10 and 13. The CAR of ‘736 also comprises the linker of instant SEQ ID NO: 3, the signal peptide of instant SEQ ID NO: 1, the transmembrane domain of instant SEQ ID NO: 6, the co-stimulatory signaling domains of both of instant SEQ ID NOs: 7 and 8, and the hinge domain of instant SEQ ID NO: 5; all with 100% sequence identity.
Application ‘736 also claims wherein the dose of CAR-T cells is 0.75 x 106 (claims 4 and 93), or 1.0 x 108 (claims 5 and 94); wherein the cells are administered, and contained in, a single cryopreserved bag (claim 6), or two cryopreserved bags (claim 8). App ‘736 claims wherein the method comprises administering a lymphodepleting regimen prior to administering the CAR-T cells (claim 12), including administering cyclophosphamide (claim 13), wherein the lymphodepleting regimen is administered IV (claim 14), whereby the lymphodepleting regimen is administered 5 to 7 days prior to the CAR-T cell infusion (claim 15), administering cyclophosphamide and fludarabine 5 to 7 days prior to CAR-T infusion (claim 16), wherein the cyclophosphamide is IV at 300 mg/m2 (claim 17), the fludarabine is administered IV at 30 mg/m2 (claim 18). App ‘736 also claims treating the subject for CRS more than 3 days following the infusion of CAR-T cells (claim 19), wherein the treatment for CRS comprises administering an IL-6R inhibitor (claim 20), which may be an antibody (claim 21), whereby the antibody inhibits IL-6R by binding its extracellular domain (claim 22), and prevents binding of IL-6 to IL-6R (claim 23), wherein the inhibitor is tocilizumab (claim 24); wherein the antipyretic comprises acetaminophen (claim 26), wherein the antipyretic is administered orally or IV (claim 27), whereby the acetaminophen is administered at a dose between 650 mg and 1000 mg (claim 28), wherein the antihistamine is diphenhydramine (claim 29), whereby the diphenhydramine is administered orally or IV (claim 30), at a dose between 25 mg and 50 mg (claim 31). App ‘736 claims wherein the CAR-T cells comprise an excipient of DMSO or dextran-40 (claim 32). App ‘736 claims wherein the subject has relapsed after at least 3 prior lines of treatment (claim 35), wherein the multiple myeloma is refractory to at least two medicaments following the at least 3 prior lines of treatment (claim 36), wherein the two medicaments comprise a PI and an IMiB (claim 37), wherein the multiple myeloma is refractory to at least 3 medicaments (claim 38), or at least four or five medicaments (claim 39). App ‘736 also claims wherein the method comprises assessing the overall response rage at a median follow-up time of at least 12 months (claim 46). App ‘736 claims wherein the T cells are autologous (claim 82), allogeneic (claim 83), wherein the subject is human (claim 84), wherein the antihistamine is administered orally, or IV, 15-45 min or 45-60 min prior to the CAR-T cells (claims 86 and 89-91), wherein the antipyretic is administered orally, or IV, 15-45 min prior to the CAR-T cells (claims 87 and 92), wherein the subject has not received a corticosteroid prior to administering the CAR-T cells (claim 88).
Therefore, as the CAR of app ‘736 SEQ ID NO: 17 anticipates that of the instant claims with 100% identity, the methods of app 736 claims 1, 4-6, 8, 12-24, 26-32, 35-39, 46, and 82-94 anticipate instant claims 1, 17, 23, 26, 34, 37 and 40; including a lymphodepleting regimen as well as treating CRS with an anti-IL-6 antibody.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 3-4, 6, 17, 23, 26-27, 34, 37, 39-40, 62-64, 67, 78 and 87-89 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4-6, 8, 12-24, 26-32, 35-39, 46, and 82-94 of copending Application No. 17/540,736 in view of Juno, (WO 2021/222330; published 11/4/2021), as evidenced by San-Miguel et al., (N Engl J Med, 2023), and as evidenced by Chng et al., (Leukemia, 2014, 28:269-277).
The reasons why claim 1, 17, 23, 26, 34, 37 and 40 are anticipated by application ‘736 are described above. Specifically, app ‘736 claims the “Cilta-cel” anti-BCMA CAR-T cells and administering the cells in a method for treating refractory multiple myeloma, wherein the subjects have received one to three prior lines of therapy.
However, app ‘736 doesn’t teach extending the methods to subjects having a high-risk feature, and the various limitations pertaining to the parameters of the high risk feature, addressing various AEs, and obtaining expected responses and outcomes.
Juno makes obvious methods of treating subjects with refractory multiple myeloma with anti-BCMA CAR-T cell therapy, whereby the subjects have had multiple lines of prior treatment, and have high risk features. Thus, Juno makes obvious administering the Cilta-cel anti-BCMA CAR-T cell therapy to “selected” high risk subjects with refractory multiple myeloma, as described above. Thus the “selected” patient population does not provide any patentable point of novelty to the instant methods.
Chng et al. provides evidence that Juno’s reference to “IMWG high risk cytogenetics”, encompasses specific del(17p) or t(4;14) genetic abnormalities, and thus these specific parameters do not provide any patentable point of novelty to the instant methods, as described above.
San-Miguel et al. provides evidence that the “Cilta-cel” anti-BCMA CAR-T cell therapy provides greater response rates as compared to standard care DPd or PVd regimens. Thus, claims to the results “obtained”, or the “effective” properties of the “Cilta-cel” anti-BCMA CAR-T cell therapy are inherent properties of the identical product and methods, and do not provide any patentable point of novelty to the instant methods, as described above.
Thus, app ‘736, claims 1, 4-6, 8, 12-24, 26-32, 35-39, 46, and 82-94, which claim the identical “Cilta-cel” anti-BCMA CAR-T cell therapy, in view of applying the therapy to selected patients with high risk features, as described by Juno, and wherein the specific parameters of the features are evidenced by Chng et al. and/or San-Miguel et al., make obvious instant claims 1, 3-4, 6, 17, 23, 26-27, 34, 37, 39-40, 62-64, 67, 78 and 87-89, for the same reasons as described above.
This is a provisional nonstatutory double patenting rejection.
Claims 1, 3-4, 6, 17, 23, 26-27, 34, 37, 39-40, 62-64, 67, 78 and 87-89 are rejected (in the case of issued patents), or provisionally rejected (in the case of pending applications) over the listed claims of the following U.S. Patents and pending applications, in view of Juno, (WO 2021/222330; published 11/4/2021), as evidenced by San-Miguel et al., (N Engl J Med, 2023), and as evidenced by Chng et al., (Leukemia, 2014, 28:269-277).
Below is a Table listing patents and/or co-pending applications, which name a common inventor, and which claim the multivariant anti-BCMA CAR of “Cilta-cel”, and a method of treating multiple myeloma, comprising administering the Cilta-cel CAR-T cells, whereby the claims would make obvious, over Juno, instant claims 1, 3-4 and 40, and all dependent claims, for the same reasons why Juno makes obvious the instant claims as described above. Specifically, as Juno makes obvious a method of treating multiple myeloma comprising administering anti-BCMA CAR-T cells, wherein the multiple myeloma is refractory, the subject has had 3 prior lines of therapy, and wherein the subject has a high-risk feature, any patent or co-pending application that claims the specific anti-BCMA CAR of “Cilta-cel”, comprising the anti-BCMA binding moieties of instant SEQ ID NOs: 2 and 4, or the full CAR construct of instant SEQ ID NO: 17, will be made obvious in a method of treating refractory multiple myeloma in selected high-risk subjects, as taught Juno, and evidenced by Chng and San-Miguel.
U.S. Patent or co-pending U.S. application
Claims
Comment
11186647
1-21
‘647 SEQ NOs: 124, 117 = instant SEQ NOs: 2, 4
18/499720
1-4, 6, 8, 13, 17-18, 22, 25, 28-30 and 32-37
‘720 SEQ NOs: 2, 4 = instant SEQ NOs: 2, 4
‘720 SEQ NO: 17 = instant SEQ NO: 17
17/740665
42-46, 55, 57-69
‘665 Cilta-cel (claim 42) = instant SEQ NO: 17
18/052349
1-4, 11, 18-19, 38, 58, 67, 87, 104, 116, 151, 189, 217, 220-225
‘349 SEQ NOs: 2, 4 (claims 189, 221) = instant SEQ NOs: 2, 4 (claim 1); and comprise ‘349 CDR SEQ NOs: 18-23 (claims 1-3)
‘349 SEQ: 17 (claim 189) = instant SEQ 17 (claim 85)
18/175347
1-9, 11-14, 19-21, 24-28
‘347 SEQ: 17 (claim 1) = instant SEQ: 17, comprises instant SEQs: 2 and 4
18/499720
1-4, 6, 8, 13, 17-18, 22, 25, 28-30, 32-37
‘720 SEQs: 2, 4 (claim 1, 3) = instant SEQs: 2, 4
‘720 SEQ: 17 (claim 17) = instant SEQ: 17
18/039420
1-2, 6, 10, 12, 19, 25, 32-33, 41, 57, 59, 82, 84-85, 90,110, 114, 122 and 128
‘420 SEQs: 2, 4, 17 (claims 1, 85) = instant SEQs: 2, 4, 17
19/315170
1-6, 8, 10, 12, 19, 25, 32-33, 41, 57 and 82-85
‘170 SEQs: 2, 4, 17 (claims 1, 85) = instant SEQs: 2, 4, 17
19/045247
1-2, 12, 14, 31, 33-34, 39-40, 45, 47, 49, 76, 81, 86, 88, 94-96, 99, 103, 107, 109, 114-119
‘247 SEQs: 2, 4, 17 (claims 1, 116) = instant SEQs: 2, 4, 17
19/076517
1-21
Specs. (pg. 9, para. 0037), teach “Ciltacabtagene autoleucel” (claim 1) is CAR of SEQ ID NO: 17.
‘517 SEQ: 17 = instant SEQ: 17, comprises instant SEQs: 2 and 4
19/409583
66-92
‘583 SEQs: 1, 3 (claim 66) = instant SEQs: 2, 4
Conclusion
No claims are allowed.
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/JAMES RYLAND MELCHIOR/Examiner, Art Unit 1644
/NELSON B MOSELEY II/Primary Examiner, Art Unit 1642
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