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 .
Claim Status
Claims 2-13 have been amended as requested in the preliminary amendment filed on 09/21/2023. Following the amendment, claims 1-13 are pending in the instant application.
Claims 1-13 are under examination in the instant office action.
Priority
Acknowledgment is made of applicant's claim for foreign priority based on a European application filed on September 26, 2022. It is noted, however, that applicant has not filed a certified copy of the EP22197771.3 application as required by 37 CFR 1.55.
Claims 1-13 have an effective filing date of September 21, 2023 corresponding to the filing date of the instant application, as the claim to foreign priority has not been perfected as no certified copy of the foreign priority document has been filed.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 10/17/2023 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code at Page 51. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Claim Objections
Claim 1 is objected to because of the following informalities: the claim lists car components using "a.", "b.", "c.", and "d." and as such the claim comprises periods that do not designate the end of a sentence or an abbreviation. Applicant may obviate this Appropriate correction is required.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 10-11 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter. The claim(s) does/do not fall within at least one of the four categories of patent eligible subject matter because the claims recite uses, but fail to recite any active steps. MPEP 2173.05(q) recites that use claims which “do not purport to claim a process, machine, manufacture, or composition of matter fail to comply with 35 U.S.C. 101. In re Moreton, 288 F.2d 708, 709, 129 USPQ 227, 228 (CCPA 1961)(‘one cannot claim a new use per se, because it is not among the categories of patentable inventions specified in 35 U.S.C. § 101’). In Ex parte Dunki, 153 USPQ 678 (Bd. App. 1967), the Board held the following claim to be an improper definition of a process: "The use of a high carbon austenitic iron alloy having a proportion of free carbon as a vehicle brake part subject to stress by sliding friction." In Clinical Products Ltd. v. Brenner, 255 F. Supp. 131, 149 USPQ 475 (D.D.C. 1966), the district court held the following claim was definite, but that it was not a proper process claim under 35 U.S.C. 101: ‘The use of a sustained release therapeutic agent in the body of ephedrine absorbed upon polystyrene sulfonic acid.’” As such, claims 10-11 are not considered to fall within at least one of the four categories of patent eligible subject matter.
Claim Rejections - 35 USC § 112
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 10-11 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.
With regard to claims 10 and 11, the claims recite “[t]he engineered cell of claim 8 for use in…”. The claims are considered to be indefinite as they are “use” claims. MPEP 2173.05(q) recites that “[a]ttempts to claim a process without setting forth any steps involved in the process generally raises an issue of indefiniteness under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph. For example, a claim which read: ‘[a] process for using monoclonal antibodies of claim 4 to isolate and purify human fibroblast interferon was held to be indefinite because it merely recites a use without any active, positive steps delimiting how this use is actually practiced. Ex parte Erlich, 3 USPQ2d 1011 (Bd. Pat. App. & Inter. 1986).” As such, claims 10-11 are considered to be indefinite as they both recite a process/use without setting forth any steps involved in the process/use.
Further with regard to claim 11, the claim recites the limitation "the cancerous cells" in line 11. There is insufficient antecedent basis for this limitation in the claim as no reference to any cancerous cells has been made and as such it is unclear as to what “the cancerous cells” is in reference to.
Claim Interpretation
It is noted that for the purposes of applying art, claims 10-11 are being interpreted as product claims, wherein the recited “use” is an intended use, wherein the recitation of the intended uses of claims 10-11 are not considered to modify, structurally or otherwise, the recited product (i.e., the engineered cells of instant claim 8).
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-3, 5-6, and 8-13 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by WO 2024/026107 A2 (herein after referred to as "Schneider").
With regard to claim 1, Schneider discloses novel chimeric antigen receptors (CARs) which may comprise single, tandem, or multi-targeting CAR constructs (including those in a DuoCAR format), or any combination thereof used to transduce effector cells for the treatment of solid and hematologic tumors and other diseases through targeted antigens wherein such a targeted antigen includes, for example, folate receptor alpha (FOLRl ) (Page 8). Novel single, tandem, DuoCAR, or multiple-targeting CARs (either with or without one or more booster elements) comprise a single, tandem, DuoCAR, or multiple-targeting CAR molecule (either with or without one or more booster elements) comprising at least one extracellular antigen binding domain comprising an anti-HER2, FOLRl, MUC16, CD276, EGFR, GD2, and/or NKGD2 antigen binding domain comprising the amino acid sequence selected from the group consisting of SEQ ID NOs: 128, 130, 132, 134, 136, 138, 140, and 142; at least one linker domain (i.e., spacer domain; see Page 77 which indicates the linker domain can include a spacer element); at least one transmembrane domain; and at least one intracellular signaling domain (Page 10; emphasis added). As such, Schneider anticipates instant claim 1.
With regard to claims 2-7, it is noted that Schneider further discloses that the transmembrane domain in the single, tandem, DuoCAR, or multiple-targeting CAR (with or without one or more boosting elements) of the invention is the CD8 transmembrane domain, which may comprise SEQ ID NO: 12 (which corresponds to the CD8α transmembrane domain). The spacer domain (comprised within the linker domain) may comprise the hinge region of CD8α (Page 78; see Schneider SEQ ID NOs: 14-15, which are the CD8α hinge domain and the CD8α hinge domain + CD8α transmembrane domain, respectively). In certain embodiments, the intracellular domain is designed to comprise the signaling domain of CD3-zeta (stimulatory domain) and the signaling domain of 4-lBB (i.e., CD137; costimulatory domain) (Page 80; see Schneider SEQ ID NOs: 18 and 20 for the amino acid sequences of the CD3-zeta stimulatory and 4-1BB costimulatory domains, respectively). Schneider further teaches that for each of the various aspects and embodiments of the single, tandem, multi-targeting, DuoCARs, (either with or without one or more booster elements) CAR, each vector encodes a functional CAR (either with or without one or more booster elements) comprising the amino acid sequence of, for example, SEQ ID NO: 225. It is specifically noted that Schneider SEQ ID NO: 225 is a 100% match to instant SEQ ID NO: 105, and more specifically comprises 100% matches to instant SEQ ID NOs: 2, 4, and 103. Thus, Schneider anticipates instant claims 2-7.
With regard to claims 8-9 and 13, Schneider further discloses a nucleic acid comprising a nucleotide sequence encoding any of the single, tandem, DuoCARs, multiple-targeting CARs (with or without one or more boosting elements), an antibody, or antigen binding portion thereof, described herein (including functional portions and functional variants thereof) wherein the nucleic acids of the invention may comprise a nucleotide sequence encoding any of the leader sequences, antigen binding domains, transmembrane domains, and/or intracellular T cell signaling domains (Page 99). In an embodiment, the nucleic acids can be incorporated into a recombinant expression vector; in this regard, an embodiment provides recombinant expression vectors comprising any of the nucleic acids (Page 105). The recombinant expression vector can be any suitable recombinant expression vector, and can be used to transform or transfect any suitable host cell (Page 106); the host cell can be of any cell type, can originate from any type of tissue, and can be of any developmental stage, the host cell may be a peripheral blood lymphocyte (PBL) or a peripheral blood mononuclear cell (PBMC), a T cell, or suitable non-T cells with immune-effector function (e.g., NK cells and T-like cells) (Page 108). Thus, Schneider further discloses nucleic acid sequences encoding a CAR comprising an antigen-binding domain specific for FOLR1, a spacer, a transmembrane domain, and an intracellular signaling domain and engineered cells expressing said CAR wherein said engineered cell may be an immune cell. As such, Schneider anticipates instant claims 8-9 and 13.
With regard to claims 10-12, it is specifically noted that the recited “uses” of the engineered cell of claim 8 in claims 10-11 are merely “intended uses” of said engineered cells. The recitation of the intended uses in claims 10-11 do not result in a structural difference of the instantly claimed engineered cells and the engineered cells of Schneider. Thus, the engineered cells of Schneider alone anticipate claims 10-11. However, it is noted that Schneider also explicitly discloses biopharmaceutical or biologics compositions for use in gene therapy, immunotherapy, adoptive immunotherapy, and/or cell therapy that include one or more of the disclosed single, tandem, DuoCARs, multiple-targeting CARs (with or without one or more boosting elements), or T cells expressing a single, tandem, DuoCAR, multiple-targeting CAR (with or without one or more boosting elements), antibodies, antigen binding fragments, conjugates, single, tandem, DuoCARs, multiple-targeting CARs (with or without one or more boosting elements), or T cells expressing a single, tandem, DuoCAR, multiple-targeting CAR (with or without one or more boosting elements) that specifically bind to one or more antigens disclosed herein, in a carrier (such as a pharmaceutically acceptable carrier) (Pages 115-116; emphasis added). Compositions including a single, tandem, DuoCAR, multiple-targeting CAR (with or without one or more boosting elements), or T cell expressing a single, tandem, DuoCAR, multiple-targeting CAR (with or without one or more boosting elements), a conjugate, antibody or antigen binding fragment of the invention are of use, for example, for the treatment and detection of a tumor, for example, and not by way of limitation, a neuroblastoma and/or a carcinoma (Page 116; emphasis added). Thus, Schneider discloses pharmaceutical compositions comprising engineered cells expressing a CAR comprising an antigen-binding domain specific for FOLR1, a spacer, a transmembrane domain, and an intracellular signaling domain and the use of said engineered cells for immunotherapy and/or the treatment of cancer. It is further noted that Schneider discloses in Figure 18C that FOLRl CARs were tested against FOLRl + line OVCAR3 (i.e., FOLR1-positive ovarian cancer cell line) and HL-60 was used as a negative control for nonspecific killing; it is noted that cell killing was only demonstrated in the FOLRl + line OVCAR3 line, not the negative control HL-60 line. Thus, Schneider further discloses using engineered cells expressing a CAR comprising an antigen-binding domain specific for FOLR1, a spacer, a transmembrane domain, and an intracellular signaling domain for the treatment of cancerous cells that are FOLR1 positive. As such, Schneider anticipates instant claims 10-12.
Claims 1, 5-6, and 8-13 are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by US 2022/0162301 A1 (herein after referred to as “Wang”).
With regard to claim 1, Wang teaches CARs, recombinant polypeptides comprising at least an extracellular domain that binds specifically to an antigen or a target, a transmembrane domain and an intracellular T cell receptor-activating signaling domain (Paragraph 0221) wherein CARs of the invention may more specifically comprise an antigen binding domain, a hinge (i.e., spacer) region, a costimulatory domain, and activating domain, and a transmembrane domain (Paragraph 0222). It is noted that the costimulatory and activating domains make up the intracellular T cell receptor-activating signaling domain. It is further noted that Wang teaches that the invention relates to chimeric antigen receptors (CAR)s comprising an antigen binding domain, wherein an antigen binding domain of the invention specifically binds FOLR1, preferably human FOLR1 (Paragraphs 0251-0268, for example). Thus, the invention of Wang is drawn to CARs comprising an antigen binding domain (that is specific to FOLR1), a hinge (i.e., spacer) region, costimulatory and activating domains (i.e., intracellular signaling domain), and a transmembrane domain. As such, Wang anticipates instant claim 1.
With regard to claims 5-6, it is further noted that Wang discloses (i) hinges of the invention may include costimulatory molecules, including CD8α (Paragraphs 0227 and 0229); (ii) various costimulatory domains that may be comprised by CARs of the invention, including 4-1BB/CD137 (Paragraph 0227) and the activating domain may be CD3ζ (Paragraph 0228); and the transmembrane domain may include CD8α (Paragraph 0230). As such, Wang discloses CARs comprising an antigen binding domain (that is specific to FOLR1), a hinge (i.e., spacer) region, costimulatory and activating domains (i.e., intracellular signaling domain), and a transmembrane domain wherein (i) the hinge may be a CD8α hinge; (ii) the costimulatory and activating domains may be 4-1BB/CD137 and CD3ζ respectively; and/or (iii) the transmembrane domain may be a CD8α transmembrane domain. As such, Wang anticipates instant claims 5-6.
With regard to claims 8-9 and 13, Wang further discloses cells that are immune cells that comprise the isolated polynucleotides or vectors comprising the isolated polynucleotides comprising the nucleotide sequence encoding the CARs of the invention, wherein said immune cells are also referred to as “engineered immune cells) (Paragraph 0231); the engineered immune cells can, for example, be cells of the lymphoid lineage wherein non-limiting examples of cells of the lymphoid lineage can include T cells and Natural Killer (NK) cells (Paragraph 0232). The invention relates to a cell transduced with the vector comprising the isolated nucleic acids encoding the CARs of the invention, wherein the cell is a CAR-T cell, preferably a human CAR-T cell, wherein the T cell is engineered to express the CAR of the invention or the cell is a CAR-NK cell, preferably a human CAR-NK cell, wherein the NK cell engineered to express the CAR of the invention (Paragraph 0350). Thus, Wang discloses engineered immune cells expressing CARs of the invention, wherein said engineered immune cells comprise the isolated polynucleotides comprising the nucleotide sequence encoding the CARs of the invention. As such, Wang anticipates instant claims 8-9 and 13.
With regard to claims 10-12, it is specifically noted that the recited “uses” of the engineered cell of claim 8 in claims 10-11 are merely “intended uses” of said engineered cells. The recitation of the intended uses in claims 10-11 do not result in a structural difference of the instantly claimed engineered cells and the engineered cells of Wang. Thus, the engineered cells of Wang alone anticipate claims 10-11. However, it is noted that Wang also discloses uses of the engineered immune cells (i.e., CAR-T cells and/or CAR-NK cells) of the invention, including in the treatment of various cancers (Paragraph 0432) wherein it is further noted that FOLRl is identified as an ideal target for CAR-T cell therapies to treat FOLRl-positive cancers (Paragraph 0248). Additionally, Wang further discloses pharmaceutical compositions comprising an isolated polynucleotide of the invention, an isolated polypeptide of the invention, a host cell of the invention, and/or an engineered immune cell of the invention and a pharmaceutically acceptable carrier (Paragraph 0426). Thus, Wang discloses engineered immune cells expressing CARs of the invention, their uses, and pharmaceutical compositions thereof. As such, Wang anticipates instant claims 10-12.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 2-3 is/are rejected under 35 U.S.C. 103 as being unpatentable over US 2022/0162301 A1 (herein after referred to as “Wang”) in view of US 2016/0015827 A1 (herein after referred to as "Lin").
With regard to claim 2, Wang teaches CARs, recombinant polypeptides comprising at least an extracellular domain that binds specifically to an antigen or a target, a transmembrane domain and an intracellular T cell receptor-activating signaling domain (Paragraph 0221) wherein CARs of the invention may more specifically comprise an antigen binding domain, a hinge (i.e., spacer) region, a costimulatory domain, and activating domain, and a transmembrane domain (Paragraph 0222). It is noted that the costimulatory and activating domains make up the intracellular T cell receptor-activating signaling domain. It is further noted that Wang teaches that the invention relates to chimeric antigen receptors (CAR)s comprising an antigen binding domain, wherein an antigen binding domain of the invention specifically binds FOLR1, preferably human FOLR1 (Paragraphs 0251-0268, for example). Thus, the invention of Wang is drawn to CARs comprising an antigen binding domain (that is specific to FOLR1), a hinge (i.e., spacer) region, costimulatory and activating domains (i.e., intracellular signaling domain), and a transmembrane domain. However, it is noted that Wang does not teach an antigen binding domain specific to FOLR1 that comprises a heavy chain variable region (VH) and a light chain variable region (VL) comprising instant SEQ ID NOs: 2 and 4, respectively. This deficiency is remedied by Lin.
Lin discloses anti-folate receptor alpha (FRA) antibody-drug conjugates comprising a hydrophilic self-immolative linker as well as compositions thereof and methods for treating cancers (Abstract). It is specifically noted that FRA is also known as FOLR1. More specifically, it is noted that Lin discloses anti-FRA antibodies that comprise a heavy chain and a light chain wherein the heavy chain comprises the amino acid sequence of SEQ ID NO: 2 and/or the light chain comprises the amino acid sequence of SEQ ID NO: 3; it is noted that Lin SEQ ID NOs: 2 and 3 comprise 100% matches to instant SEQ ID NOs: 2 and 4, respectively.
Wang and Lin are considered to be analogous to the present invention as they are in the same field of FOLR1-directed therapeutic agents. Thus, it would have been obvious to one of ordinary skill in the art to modify the CAR of Wang such that the antigen binding domain comprises an antibody of Lin wherein the antibody comprises heavy chain and a light chain wherein the heavy chain comprises the amino acid sequence of Lin SEQ ID NO: 2 and/or the light chain comprises the amino acid sequence of Lin SEQ ID NO: 3, which comprise 100% matches to instant SEQ ID NOs: 2 and 4, respectively, because the simple substitution of one known element (i.e., one FOLR1 antigen binding domain for another) would be expected to yield predictable results with a reasonable expectation of success. One of ordinary skill in the art would expect that substituting a FOLR1 antigen binding domain of Wang for that of Lin would still result in a CAR construct specific for FOLR1 which is useful for the same purpose of treating cancer.
With regard to claim 3, it is noted that Lin discloses that the term “antibody” encompasses not only intact polyclonal or monoclonal antibodies, but also antigen-binding
fragments thereof (such as Fab, Fab', F(ab')2 , Fv), single chain (ScFv), mutants thereof, fusion proteins comprising an antibody portion, and any other modified configuration of the
immunoglobulin molecule that comprises an antigen recognition site; an antibody included or used in a targeting moiety described herein (or an antibody targeting moiety) can encompass monoclonal antibodies, polyclonal antibodies, antibody fragments (e.g., Fab, Fab', F(ab')2 , Fv, Fc, etc.), chimeric antibodies, humanized antibodies, human antibodies (e.g., fully human antibodies), single chain (ScFv), bispecific antibodies, multispecific antibodies, mutants thereof,
fusion proteins comprising an antibody portion, and any other modified configuration of the immunoglobulin molecule that comprises an antigen recognition site of the required specificity (Paragraphs 0186-0187). It is further noted that Wang also discloses that humanized mAbs (specific to FOLR1) could be converted to single chain variable fragments (scFvs), each of which consists of one VH and one VL with a (G4S)n linker in between (where "n" represents the number of the G4S repeats) and either the VH or the VL region was placed at the N-terminus of the fusion protein to identify the most effective scFv designs (Example 3; Paragraph 0647); Wang further discloses Example 6 wherein to construct a CAR of the invention, each mAb is converted into a scFv, using the VH, VL and a (G4S)n linker, and the scFv is fused to the N-terminus of the hinge and transmembrane domains (Paragraph 0650). Thus, Wang suggests a CAR construct which may comprise an FOLR1-specific scFv which comprises, from N- to C- terminus, VH-linker-VL, and it would have been obvious to one of ordinary skill in the art that the antibody of Lin, comprising instant SEQ ID NOs: 2 and 4, could be modified to fit such a format as taught by Wang. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the effective filing date of the invention as evidenced by the references.
Conclusion
Claims 1-13 are pending. Claims 1-13 are rejected. No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALYSSA RAE STONEBRAKER whose telephone number is (571)270-0863. The examiner can normally be reached Monday-Thursday 7:00 am - 5:00 pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Samira Jean-Louis can be reached at (571)270-3503. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ALYSSA RAE STONEBRAKER/Examiner, Art Unit 1642
/SAMIRA J JEAN-LOUIS/Supervisory Patent Examiner, Art Unit 1642