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 .
Application Status
The amended claims filed July 17, 2024 are acknowledged. Claims 1-55 are canceled. Claims 56-75 are newly added.
Claims 56-75 are pending and under examination herein.
Specification
The disclosure is objected to for the following informalities: The abbreviation for “MSCs” does not appear to be defined in the specification. It is requested that this be added for clarity.
Appropriate correction is required.
Claim Objections
Claims 65 and 68 are objected to for the following informalities:
In claim 65, the listing of alternative immune cells contains both singular and plural options. It is requested that “gamma delta T cells” and “MSCs” be made singular for consistency. In addition, it is requested that “MSC(s)” be defined in the claim.
In claim 68, the recitation of both “one or more …” and “or a combination thereof” in the claim is redundant. It is suggested that the claim be edited for clarity.
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.
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.
Claim 71 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 71 recites the limitation "the cells" in line 1. There is insufficient antecedent basis for this limitation in the claim. The claim depends from claim 69, which recites both “CD70-positive cells” and “cells harboring the polynucleotide of claim 56”. Accordingly, the language of claim 71 does not sufficiently make clear which cells “are allogeneic or autologous with respect to the individual”.
For the purpose of compact prosecution and applying prior art under 35 U.S.C. § 102 and 103, “the cells” as recited in claim 71 will be interpreted as referring to cells harboring the polynucleotide encoding the CAR, which are administered to the individual.
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.
Claim 62 is 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.
“[T]he purpose of the written description requirement is to ‘ensure that the scope of the right to exclude, as set forth in the claims, does not overreach the scope of the inventor’s contribution to the field of art as described in the patent specification.’” Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1353-54 (Fed. Cir. 2010) (en banc) (quoting Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 920 (Fed. Cir. 2004)). To satisfy the written description requirement, the specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1562-63, 19 USPQ2d 1111 (Fed. Cir. 1991).
MPEP § 2163 states that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, or it may be satisfied by the disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. “Functional” terminology may be used “when the art has established a correlation between structure and function” but “merely drawing a fence around the outer limits of a purported genus is not an adequate substitute for describing a variety of materials constituting the genus and showing one has invented a genus and not just a species. Ariad Pharmaceuticals Inc. v. Eli Lilly & Co., 598 F3d 1336, 94 USPQ2d 1161, 1171 (Fed Cir. 2010).
For a claim to a genus, a generic statement that defines a genus of substances by only their functional activity does not provide an adequate written description of the genus. Reagents of the University of California v. Eli Lilly, 43 USPQ2d 1398 (CAFC 1997). “[A] sufficient description of a genus . . . requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can ‘visualize or recognize’ the members of the genus.” Ariad, 598 F.3d at 1350 (quoting Eli Lilly, 119 F.3d at 1568-69). A “representative number of species” means that those species that are adequately described are representative of the entire genus. AbbVie Deutschland GMBH v. Janssen Biotech, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014). Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus to provide a "representative number” of species. The “structural features common to the members of the genus” needed for one of skill in the art to ‘visualize or recognize’ the members of the genus takes into account the state of the art at the time of the invention. For example, the Federal Circuit has found that possession of a mouse antibody heavy and light chain variable regions provides a structural "stepping stone" to the corresponding chimeric antibody, but not to human antibodies. Centocor Ortho Biotech Inc. v. Abbott Labs., 97 USPQ2d 1870, 1875 (Fed. Cir. 2011).
Amgen Inc. v. Sanofi, Aventisub LLC, 872 F.3d 1367 (Fed. Cir. 2017) supported previous decisions (Centocor Ortho Biotech, Inc. v. Abbott Labs., 636 F.3d 1341 (Fed. Cir. 2011); AbbVie Deutschland GmbH & Co. v. Janssen Biotech, Inc., 759 F.3d 1285 (Fed. Cir. 2014)) that defining an antibody solely by what it binds does not satisfy the written description requirement, stating that this would allow patentees to “claim antibodies by describing something that is not the invention, i.e., the antigen”. Thus, claiming an antibody by describing the invention by what it does (function) rather than what it is (structure) is invalid. This can be overcome if a relevant number of species with structure/function correlation is known to the art or present in the specification.
The claimed invention. The nature and scope of the claimed invention at issue is the polynucleotide recited in claim 62, wherein the encoded anti-CD70 CAR comprises more than one of the 36 possible configurations set forth in (a) through (jj). While Applicant has support for single constructs encoding a CAR selected from one of the list items set forth in the claim, Applicant does not have support for polynucleotides having more than one of these constructs and/or combinations thereof.
State of the prior art. The broad goal of cancer immunotherapy is to enhance the immune response against tumor cells. As taught by Harris and Kranz (Trends in Pharmacological Sciences (2016) 37(3): 220-230), adoptive T cell therapies such as chimeric antigen receptors (CARs) have great potential for harnessing the tumor-killing properties of T cells through genetic engineering (Abstract). CAR-based adoptive T cell therapies have shown great promise and have gained the interest of biotechnology and pharmaceutical companies (Abstract; Introduction, first paragraph). Harris and Kranz teach that CARs are synthetic constructs typically comprising a single-chain antibody fragment (scFv, VH-linker-VL, or VL-linker-VH), an extracellular stalk (hinge) region, a transmembrane domain, and one or more intracellular signaling domains (page 223, “Chimeric Antigen Receptor: Structure and Signaling”). However, as illustrated by, for example, Wang (US 2018/0208671 A1; cited in IDS), Van Den Eynde (WO 2022/129216 A1; cited in IDS), Shaffer (Blood (2011) 117(16): 4304-4314; cited in IDS), Gottschalk (WO 2012/058460 A2; cited in IDS), and Park (Oral Oncol (2018) 78: 145-150; cited in IDS) in the context of anti-CD70 CARs, a CD27 extracellular domain – as opposed to an antibody-based moiety – may be used as an antigen-binding moiety. Per Harris and Kranz, “The hinge region of a CAR typically comprises either immunoglobulin-like CH2-CH3 (Fc) domains from the constant region of immunoglobulin G (IgG) or the spacer domain from either CD4 or CD8.” Lengthening or shortening the extracellular domain can optimize activity of an individual CAR (page 223). Various transmembrane regions incorporated into CARs include CD3ζ, CD28, OX40, and others (pages 223-224). The intracellular signaling domains of a CAR are derived from CD3ζ and a co-stimulatory molecule (typically CD28 or 4-1BB) (Figure 1). Harris and Kranz teach that these intracellular signaling domains have received the most attention in terms of their impact on T cell activity, T cell persistence, and efficacy. Second-generation CARs comprising co-stimulatory signaling components in concert with CD3ζ have shown improved clinical efficacy and persistence (page 224).
CAR constructs having specificity for more than one target are known in the art, but enduring challenges remain. A recent review by Gomez-Melero (Frontiers in Immunology (2025) 16: 1546172) teaches that multi-targeted CAR-T therapies like tandem CAR-T cells have emerged as a strategy to overcome clinical challenges such as antigen loss and optimal design structure, but lingering challenges such as identifying the ideal CAR construct, selecting appropriate targets, and improving transduction efficiency remain unresolved (e.g., Abstract; Sections 1-2 and 5). Xie (Cancers (2022) 14(13): 3230) further highlights challenges with multi-targeting, bispecific CAR (Bi-CAR) constructs: “Advancing technologies have made Bi-CAR T-cell therapy readily available; however, three main limitations remain for Bi-CAR T-cell therapy: (1) Bi-CAR T-cell therapy does not address other proposed resistance mechanisms outside of target antigen loss; (2) evidence on the safety profile and in vivo activity of Bi-CAR T cells are insufficient; and (3) increased difficulty in manufacturing since the size of construct is bigger. The specific challenges within Bi-CAR T cell manufacturing are the complicated optimization process to find the suitable vectors for manufacturing, increased inconsistency in batch manufacture of viral vector, low transduction efficiency in Bi-CAR T cells, and high manufacturing failure rate due to the size of the bivalent and bicistronic vector” (Section 5).
Accordingly, one of ordinary skill in the art would have recognized at the time of filing that manufacturing a CAR from a polynucleotide encoding, e.g., three, or 15, or 20, or 36 CARs (all of which are within the scope of claim 62) would be infeasible given known challenges in this field of endeavor.
Scope of species disclosed in original specification. Applicant illustrates 36 exemplary single CAR constructs (see Figure 2 and table spanning pages 9-10 of specification), all of which target CD70, comprising specific combinations of:
a signal peptide (CD27 or GMSCF-R),
an antigen-binding domain (full-length CD27, codon-optimized full-length CD27, truncated CD27, or codon-optimized truncated CD27),
a transmembrane domain (CD27, codon-optimized CD27, CD28, or codon-optimized CD28), and
one, two, or three intracellular domains (comprising selected combinations of CD3ζ, CD27 intracellular domain, codon-optimized CD27 intracellular domain, CD28 intracellular domain, 4-1BB, DAP10, DAP12, and/or NKG2D).
The transfection efficiency of said constructs in 293T cells and in cord blood-derived NK cells is shown in Figures 3-4. The constructs exhibited varying levels of specificity and killing activity against CD70-positive cells (e.g., Figures 5 and 7-9).
The disclosure does not recite polynucleotides or CAR constructs comprising two or more of the individual embodiments set forth in Figure 2 and/or the table on pages 9-10.
MPEP § 2163 states that a “representative number of species” means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. In the absence of a representative number of species, the written description requirement for a claimed genus may be satisfied by disclosure of relevant, identifying characteristics; i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus.
While Applicant has written support for the polynucleotides encoding one of 36 single-targeting CAR constructs set forth in the disclosure, Applicant does not have support for polynucleotides encoding two or more of the exemplary CAR constructs as set forth under the broadest reasonable interpretation of claim 62.
Conclusion. For all of the reasons presented above, one of skill in the art would not know which of the countless polynucleotides encoding multiple anti-CD70 CARs as encompassed by the highly general structural requirements of the claims would also possess the required functional activity given known challenges in the field with respect to preferential expression, manufacturing, and in vivo safety and efficacy, among others. Given the limited number of species described and the fact that the species that were described cannot be considered representative of the broad genus, the Applicant did not possess all of the possible polynucleotide constructs as broadly claimed at the time the application was filed.
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.
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.
Claims 56-57, 59-62, and 64-75 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Wang (US 2018/0208671 A1; cited in IDS).
Wang discloses CARs having antigenic specificity for CD70, as well as host cells, recombinant expression vectors, and nucleic acids encoding said CARs and methods of using said CARs for treating cancer (e.g., Abstract). Regarding claims 56, 59-60, and 62, Wang discloses a nucleic acid encoding an anti-CD70 CAR comprising an antigen-binding-transmembrane domain comprising a CD27 amino acid sequence lacking all or a portion of the CD27 intracellular T cell signaling domain, a 4-1BB (CD137) intracellular T cell signaling domain, a CD3ζ intracellular T cell signaling domain, and optionally a CD28 intracellular T cell signaling domain (e.g., Abstract; ¶ 0004-0007, 0048-0059; claims 1-12).
Exemplary CARs of the invention of Wang comprise one of the amino acid sequences of SEQ ID NO: 7-13 (e.g., ¶ 0004-0007, 0038; Table 1A; claim 10). The CARs comprising the amino acid sequences of SEQ ID NO: 7, 8, 9, 10, 11, 12, and 13 each comprise the anti-CD70 antigen-binding domain comprising instant SEQ ID NO: 2 (at positions 1-191) and the CD27 signal peptide comprising instant SEQ ID NO: 6 (at positions 1-19), anticipating claim 57 and 60 (and relevant to claim 61). Further regarding claim 61, the CAR constructs comprising the amino acid sequences of SEQ ID NO: 7 and 11-13 also comprise the transmembrane domain having the amino acid sequence of instant SEQ ID NO: 7 (at positions 192-212), and the CAR constructs comprising the amino acid sequences of SEQ ID NO: 9, 10, 12, and 13 comprise a 4-1BB intracellular signaling domain comprising the amino acid sequence of SEQ ID NO: 5 (e.g., ¶ 0037-0039), which shares 100% sequence identity to instant SEQ ID NO: 12.
Regarding claims 64-68, Wang discloses that suitable host cells expressing the anti-CD70 CAR of the invention include T cells (e.g., ¶ 0065-0069). (It is noted that claim 66-68 set forth further limitations when the immune cell is an NK cell, but do not require that the immune cell is an NK cell if another limitation (e.g., a T cell) is met.) Wang states that when expressed in T cells, “CARs advantageously do not dimerize with endogenous T cell receptor (TCR) alpha and beta chains” (¶ 0019).
Regarding claims 69-72 and 74, Wang discusses a method of treating cancer in a mammal that comprises intravenously administering a population of cells (e.g., allogeneic or autologous) encoding a CAR of the invention, thereby targeting and destroying CD70-expressing cancer cells (e.g., ¶ 0020-0022, 0065-0082; claims 1, 12-16, and 20). Regarding claim 75, Wang provides a method of detecting the presence of cancer in a mammal that comprises (a) contacting a sample comprising one or more cells from the mammal with a cell or population of cells comprising CAR of the invention to form a complex and (b) detecting said complex (e.g., ¶ 0085-0091). Wang states that the contacting can take place in vivo, which would necessarily require administering the cells to the mammal.
Regarding claim 73, Wang discloses that the CARs of the invention can be administered with an additional therapeutic agent such as IL-2 (i.e., an immunotherapy) or can be co-formulated with other pharmaceutically active drugs such as chemotherapeutic agents or antibodies (e.g., ¶ 0070-0078).
Claims 56-62 and 64-74 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Van Den Eynde (WO 2022/129216 A1; filed December 15, 2021; earliest priority date: December 15, 2020; cited in IDS).
Van Den Eynde discloses natural killer (NK) cells engineered to express a nucleic acid encoding an anti-CD70 CAR comprising an extracellular domain of CD27, a transmembrane domain, and an intracellular signaling domain (e.g., Abstract; pages 1-2, 7-28), anticipating claims 56 and 64-65. In one embodiment, the CAR of the invention comprises an amino acid sequence of SEQ ID NO: 9, which comprises the signal peptide comprising the amino acid sequence of instant SEQ ID NO: 6, the CD27 extracellular domain comprising the amino acid sequence of instant SEQ ID NO: 2, a 4-1BB (CD137) intracellular domain sharing 100% sequence identity to instant SEQ ID NO: 7, and a CD3ζ intracellular activation domain sharing 100% sequence identity to instant SEQ ID NO: 12 (e.g., page 18), anticipating claims 57 and 59-62. Regarding claim 58, Van Den Eynde provides that the CARs of the invention may also use a transmembrane domain other than CD27 such as a CD8α transmembrane domain, optionally with a CD8α hinge (e.g., page 15).
Regarding claims 64-67, Van Den Eynde teaches that the NK cells expressing a CAR of the invention may be derived from induced pluripotent stem cells (iPSCs), umbilical cord blood, or other sources and detected by their expression of CD56 surface markers (e.g., pages 26-27). Regarding claim 68, Van Den Eynde teaches that the NK cells may be engineered to further express one or more immunostimulatory cytokines such as IL-15, IL-12, and/or IL-21 (e.g., page 28). Van Den Eynde notes that NK cells lack both TCR rearrangement and T cell, B cell, monocyte and/or macrophage cell surface markers (page 27).
Regarding claims 69-70, Van Den Eynde discloses that a therapeutically effective amount of the CAR-expressing NK cells of the invention may be administered to a subject in need thereof to treat a CD70-expressing cancer and kill CD70-positive cancerous cells (e.g., pages 2, 55-57). Van Den Eynde recites that the NK cells may be autologous or allogeneic relative to the subject to whom they are to be administered (e.g., page 27), anticipating claim 71. Van Den Eynde further teaches that pharmaceutical compositions comprising the CAR-expressing NK cells of the invention may be administered systemically by injection via a kit (e.g., pages 43-44), anticipating claims 72 and 74. Regarding claim 73, Van Den Eynde teaches that the engineered NK cells of the invention may be administered in combination with another anti-cancer therapy such as surgery, a hormone therapy, or an antibody (e.g., pages 50-52).
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 56, 58, and 64-68 are rejected under 35 U.S.C. 103 as being unpatentable over Wang (US 2018/0208671 A1; supra) as applied to claims 56-57, 59-62, and 64-65 above, and further in view of Van Den Eynde (WO 2022/129216 A1; supra).
The teachings of Wang are discussed in the 35 U.S.C. § 102 rejection above.
However, Wang does not expressly recite expressing a CAR of the invention in an NK cell, nor that the transmembrane domain of the CAR may comprise, e.g., CD8α.
The teachings of Van Den Eynde are discussed in the 35 U.S.C. § 102 rejection above.
It would have been obvious to one of ordinary skill in the art, before the filing date of the instantly claimed invention, to (1) modify a CAR construct taught by Wang by substituting a CD8α transmembrane domain, and (2) express a CAR construct of the invention in an NK cell (e.g., a CD56+ and/or cord blood-derived NK cell), based on the teachings of Van Den Eynde. The skilled artisan would have been motivated to do so because (1) a CD8α transmembrane domain would be similarly suitable as a transmembrane domain, and (2) because NK cells also have cytotoxic properties and may be further modified by exogenous expression of cytokines to further improve their function. There would have been a reasonable expectation of success because those of ordinary skill in the art would recognize the suitability of either of these substitutions for the intended purpose of generating a CAR-expressing immune cell that has cytotoxic activity against CD70-expressing cancer cells. Furthermore, Wang and Van Den Eynde set forth materially identical CAR constructs (e.g., as set forth in claim 61 and 62), and use of such a CAR construct in either of a T cell or an NK cell would constitute a simple substitution of one known element for another to obtain predictable results.
Claims 56, 64-64, 69, and 75 are rejected under 35 U.S.C. 103 as being unpatentable over Van Den Eynde (WO 2022/129216 A1; supra) as applied to claims 52-62 and 64-74 above, and further in view of Wang (US 2018/0208671 A1; supra).
The teachings of Van Den Eynde are discussed in the 35 U.S.C. § 102 rejection above.
However, Van Den Eynde does not expressly teach expressing a CAR of the invention in a T cell, nor a method of killing CD70-positive cells in an individual that further comprises the step of identifying CD70-positive cells in the individual.
The teachings of Wang are discussed in the 35 U.S.C. § 102 rejection above.
It would have been obvious to one of ordinary skill in the art, before the filing date of the instantly claimed invention, to (1) express a CAR construct taught by Van Den Eynde in a T cell, and (2) carry out the steps of administering a therapeutically effective amount of cells expressing a CAR of the invention to an individual in need thereof and further identifying CD70-positive cells in an individual, based on the further teachings of Wang. The skilled artisan would have been motivated to do so because T cells also have cytotoxic properties, and when expressed in T cells, CARs advantageously do not dimerize with endogenous TCR, as provided by Wang. Further, one would have been motivated to perform the additional step of identifying CD70-positive cells in the treated individual to confirm the presence of CD70-positive cells before treatment or identify whether the treatment was effective afterward. There would have been a reasonsable expectation of success because Wang and Van Den Eynde set forth materially identical CAR constructs (e.g., as set forth in claim 61 and 62), and use of such a CAR construct in either of a T cell or an NK cell would constitute a simple substitution of one known element for another to obtain predictable results.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 56-62 and 64-75 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 158-177 of co-pending Application No. 18/700,483 in view of Wang (US 2018/0208671 A1; supra).
Relevant to claim 56, 58-59, and 62, co-pending claims 158 and 162 recite one or more polynucleotides encoding one or more antigen-specific receptors, each comprising (a) one or more antigen binding domains, specific for CD70; (b) a transmembrane domain selected from CD28 and others; (c) one or more intracellular domains comprising CD3ζ, DAP10, DAP12, and others. Relevant to claims 60 and 62, co-pending claim 165 recites that the one or more polynucleotides further encodes a signal peptide (CD27 or GMSCF-R).
Relevant to claims 64-68, co-pending claims 166-170 recite that the one or more polynucleotides further encode a cytokine (e.g., IL-15, IL-2, IL-12, etc.), as well as an immune cell (e.g., cord blood-derived NK cell, T cell, etc.) expressing the one or more polynucleotides and a recombinant cytokine (e.g., IL-15, IL-2, IL-12, etc.).
Co-pending claim 172 additionally recites a pharmaceutical composition comprising the immune cell of co-pending claim 168. Co-pending claims 173 and 177 recite a method that comprises the step of administering a therapeutically effective amount of immune cells having enhanced metabolic fitness to a subject having cancer, thereby decreasing tumor burden.
However, the co-pending claims do not recite that the anti-CD70 antigen-binding domain(s) are a CD27 extracellular domain, or that the constituent parts of the CAR comprise the respective amino acid sequences set forth in claims 57 or 61. The co-pending claims also do not expressly recite administering to a subject in need thereof immune cells expressing the anti-CD70 CAR.
The teachings of Wang are recited in the 35 U.S.C. § 103 rejection above.
It would have been obvious to one of ordinary skill in the art, before the filing date of the instantly claimed invention, to substitute into a polynucleotide encoding a CAR construct of the co-pending claims the specifically enumerated CD27 extracellular domain comprising the amino acid sequence of instant SEQ ID NO: 2, a signal peptide comprising the amino acid sequence of instant SEQ ID NO: 6, a transmembrane domain comprising instant SEQ ID NO: 7, and an intracellular domain comprising the amino acid sequence of instant SEQ ID NO: 12, as set forth by Wang. The skilled artisan would have been motivated to do so because said CAR construct would have utility in treating and detecting CD70-expressing cancers. There would have been a reasonable expectation of success because those of ordinary skill in the art would recognize that the CAR components described by Wang are functionally equivalent and have utility for materially the same desired purpose.
This is a provisional nonstatutory double patenting rejection.
Claims 56-62 and 64-74 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 158-177 of co-pending Application No. 18/700,483 in view of Van Den Eynde (WO 2022/129216 A1; supra).
The teachings of the co-pending claims are summarized in the non-statutory double patenting rejection above.
However, the co-pending claims do not recite that the anti-CD70 antigen-binding domain(s) are a CD27 extracellular domain, or that the constituent parts of the CAR comprise the respective amino acid sequences set forth in claims 57 or 61. The co-pending claims also do not expressly recite administering to a subject in need thereof immune cells expressing the anti-CD70 CAR.
The teachings of Van Den Eynde are recited in the 35 U.S.C. § 103 rejection above.
It would have been obvious to one of ordinary skill in the art, before the filing date of the instantly claimed invention, to substitute into a polynucleotide encoding a CAR construct of the co-pending claims the specifically enumerated CD27 extracellular domain comprising the amino acid sequence of instant SEQ ID NO: 2, a signal peptide comprising the amino acid sequence of instant SEQ ID NO: 6, a transmembrane domain comprising instant SEQ ID NO: 7, and an intracellular domain comprising the amino acid sequence of instant SEQ ID NO: 12, as set forth by Van Den Eynde. The skilled artisan would have been motivated to do so because said CAR construct would have utility in treating and detecting CD70-expressing cancers. There would have been a reasonable expectation of success because those of ordinary skill in the art would recognize that the CAR components described by Van Den Eynde are functionally equivalent and have utility for materially the same desired purpose.
This is a provisional nonstatutory double patenting rejection.
Allowable Subject Matter
Claim 63 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Elizabeth A Shupe whose telephone number is (703) 756-1420. The examiner can normally be reached Monday to Friday, 9:30am - 6:00pm EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Julie Wu can be reached at (571) 272-5205. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/ELIZABETH A SHUPE/Examiner, Art Unit 1643
/Brad Duffy/Primary Examiner, Art Unit 1643