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 .
Applicant’s amendment, filed on 6/08/2026, is acknowledged.
Claims 1-68 are currently pending.
Claims 1, 2, 16, 28, 39, 50, and 61 are independent claims.
Election/Restrictions
Applicants’ election without traverse of Group I, claims 1-15, 17-27, and 46, directed to an engineered cell comprising a CAR and a therapeutic peptide; and the species of: i) SEQ ID NO: 8; ii) the target of CD19; iii) a CD8α TM domain; iv) a CD3ζ ICD, and v) a 4-1BB costimulatory domain, filed on 6/08/2026, is acknowledged.
Claims 3-5, 7, 12, 23, and 24 are drawn to unelected species of therapeutic peptides.
Claim 18 is drawn to an unelected species of target.
Claims 3-5, 7, 12, 16, 18, 23, 24, 28-45, and 47-68 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to nonelected inventions.
After consideration, the search and examination has been extended to the other species of therapeutic peptide sequences (i.e., the other sequences recited in instant claim 10).
Claims 1, 2, 6, 8-11, 13-15, 17, 19-22, 25-27, and 46 are under examination as reading on an engineered cell comprising a CAR and a therapeutic peptide.
Priority
Applicant’s claim for the benefit of a prior-filed U.S. Provisional Patent Application No. 63/166,073 filed March 25, 2021, is acknowledged.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 3/01/2024, 3/25/2025, and 5/20/2026 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner in their entireties.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency 1 - The Incorporation by Reference paragraph required by 37 CFR 1.821(c)(1) is missing or incomplete. See item 1) a) or 1) b) above.
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required incorporation-by-reference paragraph, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Specific deficiency 2 – Nucleotide and/or amino acid sequences appearing in the specification are not identified by sequence identifiers in accordance with 37 CFR 1.821(d).
Specifically, amino acid sequences without the corresponding sequence identifiers are disclosed in the following locations: pg. 9, lines 13, 28, 29; pg. 11, lines 22, 23, and 27; pg. 12, line 11; pg. 116, lines 3, 4, 6, 8, 12 and 26; pg. 119, lines 12, 13, 17, 20, 23, and 27; pg. 120, lines 2 and 6; and pg. 121, line 19
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Claim Objections
Claims 25 and 46 are objected to for the following reasons:
Claims 25 recites the acronym “PRR”, which is not a readily recognized acronym in the art, such as “DNA” for 5’-deoxyribonucleic acid. Please define the acronym “PRR” when it is first used in the claims.
Claim 46 is objected to because it is dependent on a non-elected claim 45 and should be written as an independent claim.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1, 2, 6, 8-11, 13-15, 17, 19-22, 25-27, and 46 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claims 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 inventors, at the time the application was filed, had possession of the claimed invention.
Claims 1, 2, 6, 8-11, 13-15, 17, 19-22, 25-27, and 46 encompass engineered cells comprising a broad genus of peptides with no recited structure and the functions of “non-natural therapeutic peptide” (claims 1, 2, 8, 9, 11, 13-15, 17, 19-22, 25-27, and 46) or “SMAC mimetic” (claim 6).
Additionally, claim 25 encompasses a broad genus of cells further comprising RNA molecules with no recited structure and the function of “activates a PRR”.
However, the specification fails to provide adequate written description support for a genus of antibody heavy chain constant regions with no recited structure having the desired functional properties required to practice the claimed functions of “non-natural therapeutic peptide” (claims 1, 2, 8, 9, 11, 13-15, 17, 19-22, 25-27, and 46) or “SMAC mimetic” (claim 6); or a broad genus of RNA molecules with no recited structure and the function of “activates a PRR” (claim 25).
The claims are not supported by a description that satisfies 35 U.S.C. § 112(a) or 35 U.S.C. § 112, first paragraph. "[T]he test for sufficiency [of the written description] is whether the disclosure of the application relied upon reasonably conveys to those skilled in the art that the inventor had possession of the claimed subject matter as of the filing date." Ariad Phanns., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1351 (Fed. Cir. 2010) (en bane).
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." Id. at 1350. "[A]n adequate written description requires a precise definition, such as by structure, formula, chemical name, physical properties, or other properties, of species falling within the genus sufficient to distinguish the genus from other materials." Id.
"[F]unctional claim language can meet the written description requirement when the art has established a correlation between structure and function." Id. "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 that one has invented a genus and not just a species." Id.
"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" (AbbVie, 759 F.3d at 1297, reiterating Eli Lilly, 119 F.3d at 1568-69) (emphasis added).
The specification discloses modification of CAR-T cells engineered to express an additional peptide (Examples 1-6). These peptides include the ovalbumin epitope SIINFEKL (SEQ ID NO: 7), which complexes with MHC (Example 1). This was found to be transferred to T-cells that are not expressing this MHC complex (Example 1, Fig. 4).
The specification further discloses identification of STING agonist mimetic peptides were also co-expressed with CARs in T-cells (Example 2, Fig. 17): “[s]ix cGAMP mimetic peptides (also referred to herein as STING peptides) were selected…nucleic acid segment encoding the ST2 peptide and the nucleic acid encoding the 19BBz CAR molecule, to generate CD19 CAR-T cells with ST2 peptide…[t]he presence of the cGAMP mimetic, STING agonist peptides in the context of a CAR-T cell therapy significantly improved the anticancer effect of the CAR-T cells…”
The specification further discloses identification of SMAC mimetic peptides which were also co-expressed with CARs in T-cells (Example 3, Fig. 21): “SMAC peptides were generated using a rational design strategy. Peptides with the best binding and potency (as measured by induction of cell death) in a dose response assay were selected for testing…[p]eptide 6 (SMACm6; SEQ ID NO: 8) was selected for further analysis based on dose response in multiple cell lines…the study showed that a peptide that triggers a TNF-dependent cell death pathway that has shown limited utility as a target in clinical studies but can act as a potent mediator of cell death in certain contexts, can be delivered by CAR-T cell therapy and significantly improve the efficacy of the CAR-T cell therapy…”
Additionally, the specification discloses identification of PARP inhibitor peptides which were also co-expressed with CARs in T-cells (Example 4, Fig. 25): “PARP inhibitor peptides were computationally designed…PARPi mimetic peptides (Pep 1, PeplC, Pep2, and Pep3; SEQ ID NOs: 13, 14, 15, and 16, respectively) increased PD-L 1 expression… the study showed that the computationally designed, novel PARPi mimetic peptides induce a DNA damage response that will lead to cancer cell death…”
The specification discloses all of the therapeutic peptide structures expressed in CAR-T cells (Table 1):
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The specification further discloses co-expression of CARs in T-cells as well as the S7L RNA structure (pg. 118): “…a CAR containing a combination of the Ova peptide and the RNA RN7SL1 (7SL); see construct in FIG. 12A. 7SL is a highly structured RNA that functions as an intratumoral PAMP and activates PRR signaling…”
With respect to representative number of species, see AbbVie Deutschland GmbH & Co. v. Janssen Biotech, Inc. (Fed. Cir. 2014). Also, see MPEP 2163 Il(A)(3)(a))(ii):
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. 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. See Abb Vie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (Claims directed to a functionally defined genus of antibodies were not supported by a disclosure that "only describe[d] one type of structurally similar antibodies" that "are not representative of the full variety or scope of the genus.").
Satisfactory disclosure of a "representative number" depends on whether one of skill in the art would recognize that the applicant was in possession of the necessary common attributes or features possessed by the members of the genus in view of the species disclosed. For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus. See, e.g., Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. Instead, the disclosure must adequately reflect the structural diversity of the claimed genus, either through the disclosure of sufficient species that are "representative of the full variety or scope of the genus," or by the establishment of "a reasonable structure-function correlation." Such correlations may be established "by the inventor as described in the specification," or they may be "known in the art at the time of the filing date." See AbbVie, 759 F.3d at 1300-01, 111 USPQ2d 1780, 1790-91 (Fed. Cir. 2014) (Holding that claims to all human antibodies that bind IL-12 with a particular binding affinity rate constant (i.e., koff) were not adequately supported by a specification describing only a single type of human antibody having the claimed features because the disclosed antibody was not representative of other types of antibodies in the claimed genus, as demonstrated by the fact that other disclosed antibodies had different types of heavy and light chains, and shared only a 50% sequence similarity in their variable regions with the disclosed antibodies.).
In the instant case, the application is claiming 15 non-natural therapeutic peptides generated from screening computationally derived peptide candidates, which are 6 cGAMP TLR agonist mimetic peptide structures, 5 SMAC mimetic peptide structures, and 4 PARPi mimetic peptide structures (Table 1). These limited number of peptide structures, defined be their amino acid sequences, do not sufficiently represent the broadly claimed genus of peptide structures with the function of “non-natural therapeutic peptide” (claims 1, 2, 8, 9, 11, 13-15, 17, 19-22, 25-27, and 46) or “SMAC mimetic” (claim 6). For example, claims 1, 2, 8, 9, 11, 13-15, 17, 19-22, 25-27 encompass peptide structures that are therapeutic but are not cGAMP, SMAC, or PARPi inhibitors, such as peptide toxins, tumor homing peptides, cell penetrating peptides, or any other peptide structure with any therapeutic effect.
Additionally, regarding the broadly claimed RNA structures with the function of “activates a PRR” (claim 25), the instant specification discloses only one specific RNA structure with this function, the 7SL RNA structure. This one RNA structure does not sufficiently represent the broadly claimed class of RNA molecules of any length and sequence with the claimed function.
Moreover, there is insufficient written description of the required kind of structure-identifying information about the corresponding makeup of the claimed non-natural therapeutic peptide or RNA constructs to demonstrate possession. Also, see Amgen Inc. v. Sanofi, Aventisub LLC, No. 2017-1480 (Fed. Cir. 2017). The Court reiterated that adequate written description must “contain enough information about the actual makeup of the claimed products . . . .” The Court simultaneously suggested that the “newly characterized antigen” test “flouts” section 112 because it “allows patentees to claim antibodies by describing something that is not the invention, i.e., the antigen.” The Court concluded that for written description of an antibody to be adequate when presented with “functional” terminology, there must be an established correlation in the art between structure and function.
Given the broadly claimed classes claimed non-natural therapeutic peptide or RNA constructs, and in the absence of sufficient disclosure of relevant identifying characteristics for the broadly claimed classes of peptide structures with the function of “non-natural therapeutic peptide” (claims 1, 2, 6, 8, 9, 11, 13-15, 17, 19-22, 25-27, and 46) or “SMAC mimetic” (claim 6), the patentee must establish “a reasonable structure-function correlation” either within the specification or by reference to the knowledge of one skilled in the art with functional claims. AbbVie Deutschland GmbH & Co. v. Janssen Biotech, Inc. (Fed. Cir. 2014), MPEP 2163.
Regarding the broadly claimed classes of peptide structures with the function of “non-natural therapeutic peptide” (claims 1, 2, 6, 8, 9, 11, 13-15, 17, 19-22, 25-27, and 46) or “SMAC mimetic” (claim 6), or RNA structures with the function of “activates a PRR” (claim 25), the specification at best describes plan for making additional peptide structures with the claimed functions, and then identifying those that satisfy the claim limitations, but a mere “wish or plan” for obtaining claimed invention is not sufficient. Centocor Ortho Biotech Inc. v. Abbott Laboratories, 97 USPQ2d 1870 (Fed. Cir. 2011).
The specification only discloses a limited number of peptide structures, defined by their amino acid sequences, within the claimed scope. The specification provides no direction or guidance regarding how to produce antigen binding constructs with the function of “non-natural therapeutic peptide” (claims 1, 2, 6, 8, 9, 11, 13-15, 17, 19-22, 25-27, and 46) or “SMAC mimetic” (claim 6) as broadly defined by the claims. The only guidance the disclosure provides is to list specific structures with these functions.
Additionally, the prior art teaches that there is unpredictability between a peptide amino acid sequence and the function of “non-natural therapeutic peptide”, including SMAC mimetics. For example, Oost et al. (J Med Chem. 2004 Aug 26;47(18):4417-26. doi: 10.1021/jm040037k) teaches that peptide variants based on the SMAC peptide (i.e., “SMAC mimetics”) varied in binding affinity based on amino acid sequences (Table 1), with some substitutions increasing binding affinity while others reduced (see, for example, mutations to Gly and Lys in position 2 in Table 1).
Regarding the broadly claimed RNA structures with the function of “activates a PRR” (claim 25) the specification only discloses one RNA structure with this recited function and the specification provides no direction or guidance regarding how to produce RNA structures with the claimed function of “activates a PRR”. The only guidance the disclosure provides is to list the 7SL RNA structure with this functions.
Possession is not be shown by merely describing how to obtain possession of members of the claimed genus or how to identify their common structural features. See University of Rochester, 358 F.3d at 927, 69 USPQ2d at 1895. Sufficient description to show possession of such a genus may be achieved by means of a recitation of a representative number of non-natural therapeutic peptides or RNA constructs falling within the scope of the genus or of a recitation of structural features common to members of the genus, which features constitute a substantial portion of the genus. See Eli Lilly, 119F.3d at 1568, 43 USPQ2d at 1406.
Claims 1, 2, 6, 8, 9, 11, 13-15, 17, 19-22, 25-27, and 46 do not meet the requirements of 35 U.S.C. 112(a) for written description.
Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, makes clear that "applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the written description inquiry, whatever is now claimed." (See page 1117.) The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed." (See Vas-Cath at page 1116.). Consequently, Applicant was not in possession of the instant claimed invention. See University of California v. Eli Lilly and Co. 43 USPQ2d 1398.
Applicant is invited to point to clear support or specific examples of the claimed invention in the specification as-filed.
To overcome this rejection, it is recommended the amend the claims 1 and 2 to recite specific peptide structures, defined by their amino acid sequence, with the claimed functions; and amend claim 25 to recite specific RNA structures with the function of “activates a PRR”.
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 8 and 9 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.
Claims 8 and 9 recite: “…wherein the non-natural peptide is a peptide that has no more than…sequence identity to a naturally occurring peptide.” The claims are indefinite because it is currently unclear which structural features should be used for comparison. It is indefinite to compare amino acids between two molecules without structural features for the comparison.
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, 2, 13-15, 20, and 27 are rejected under 35 U.S.C. 102(a)(1)/(2) as being anticipated by Suarez et al. (Oncotarget. 2016 Jun 7;7(23):34341-55. doi: 10.18632/oncotarget.9114).
Claim 1 recites an engineered cell comprising a CAR and a therapeutic peptide, wherein the therapeutic peptide is non-natural and the CAR and peptide are expressed from the same expression construct. Claim 2 recites the same cell, however the CAR and therapeutic peptide do not need to be expressed from the same construct.
Suarez et al. teaches T-cells genetically modified to express a CAR and a PD-L1 antibody (i.e., “a non-natural therapeutic peptide”; the limitations of instant claim 14), wherein the CAR and antibody are expressed on the same construct (Abstract): “…we used a single bicistronic lentiviral vector to develop a new combination immunotherapy that consists of human anti-carbonic anhydrase IX (CAIX)-targeted chimeric antigen receptor (CAR) T cells engineered to secrete human anti-programmed death ligand 1 (PD-L1) antibodies at the tumor site…”
Suarez et al. teaches the CAR comprises an anti-CAIX or BCMA scFv (i.e., the limitations of instant claim 15) antigen binding domain, a linker, a CD28 TM domain, and an intracellular signaling domain comprising CD28 and CD3ζ signaling domains (Fig. 1):
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Therefore, Suarez et al. teaches the limitations of instant claims 1 and 2.
Regarding instant claim 13, Suarez et al. teaches that CAIX is expressed on tumor cells (pg. 34342): “CAIX was chosen as a target to our CAR because this enzyme is overexpressed in many hypoxic solid tumors…”, meeting the claim limitations.
Regarding instant claim 20, Suarez et al. teaches the ICD comprising a CD3ζ signaling domain (see supra), meeting the claim limitations.
Regarding instant claim 27, Suarez et al. teaches compositions comprising the engineered cells in culture medium (“Methods”): “5×104 skrc59 CAIX+/PD-L1+ cells were suspended in 10 μL of culture medium…”, meeting the claim limitations.
The reference teachings anticipate the instant claimed invention.
Claim Rejections - 35 USC § 103
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 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.
Claims 1, 2, 6, 10, 13-15, 20, and 27 are rejected under 35 U.S.C. 103 as being unpatentable over Suarez et al. (Oncotarget. 2016 Jun 7;7(23):34341-55. doi: 10.18632/oncotarget.9114, supra) in view of Michie et al. (Cancer Immunol Res. 2019 Feb;7(2):183-192. doi: 10.1158/2326-6066.CIR-18-0428) and Bilim et al. (Br J Cancer. 2008 Mar 11;98(5):941-9. doi: 10.1038/sj.bjc.6604268).
The teachings of Suarez et al. is discussed in the 35 U.S.C. § 102 rejection supra. Suarez et al. additionally teaches that the CAR-T cell co-expressing additional therapeutics such as antibodies are useful due to the local delivery of high concentration of such a therapeutic to a solid tumor milieu and can also result in less systemic effects for the same reason (Discussion): “…armed second-generation anti-CAIX CAR T cells constitutively secreting anti-PD-L1 IgGs that are retained in the RCC milieu also show reduced T cell exhaustion and enhanced anti-tumor activity. It is possible that this single combination anti-cancer agent that delivers persistently high local concentrations of the anti-PD-L1 mAbs may provide a significant treatment advantage for solid tumors. The local expression of anti-PD-L1 mAb may also result in reduced systemic toxicity…”
Suarez et al. does not teach the CAR-T cell expressing a SMAC mimetic peptide (i.e., the limitations of instant claim 6).
Michie et al., in the same field of endeavor, teaches that antagonism of IAPs enhance CAR-T cell efficacy (Title). Michie et al. teaches that SMAC inhibitors enhance tumor cell death in the presence of CAR-T cells (Fig. 2, pg. 187): “…cell death was measured using a chromium release killing assay. In all cell lines, a significant increase in cell death in the presence of birinapant compared with vehicle was observed…”
Thus, Michie et al. teaches that SMAC inhibitors enhance CAR-T cell killing of tumor cells, providing motivation to further modify the CAR-T cell of Suarez et al. to express a SMAC inhibitor for local delivery at the tumor site. However, Michie et al. does not teach a peptide SMAC inhibitor that can be expressed by the CAR-T cell (i.e., the limitations of instant claim 6).
Bilim et al., in the same field of endeavor, teaches a SMAC-N7 peptide that increases renal cell carcinoma sensitivity to apoptosis (Abstract): “…[o]ur results suggest that multiple targeting of both Bcl-2 and XIAP or, alternatively, of several IAP family members by the Smac-N7 peptide is a potent way to overcome resistance of RCC to apoptosis-triggering treatment modalities, and might be a new tool for molecular targeted therapy.” Bilim et al. further teaches methods of engineering cells to express the SMAC mimetic peptide SMAC-N7 (“Peptide transfection” section).
It would have been obvious to one with ordinary skill in the art, before the effective filing date of the instant application, to have modified the invention of Suarez et al. in view of Michie et al. and Bilim et al. to have engineered the CAR-T cells of Suarez et al. to further express the SMAC-N7 peptide with a reasonable expectation of success (i.e., the limitations of instant claim 6), as Bilim et al. teaches methods of expressing the SMAC-N7 therapeutic peptide that one with ordinary skill in the art could adapt to express in the CAR-T cells of Suarez et al.. For example, one could engineer the vector of Suarez et al. to further encode the SMAC-N7 peptide with an upstream IRES element. One would have been motivated to make this change to engineer a CAR-T cell that express both a PD-L1 antibody and SMAC-N7 peptide to allow for local delivery of these therapeutics at the tumor site to enhance CAR-T cell efficacy in inhibiting tumor growth.
Regarding instant claim 10, Bilim et al. teaches the SMAC-N7 peptide comprises the sequence of AVPIAQK (Abstract), which comprises an amino acid sequence that is 100% identical to instant SEQ ID NO: 9, meeting the claim limitations:
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Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Claims 1, 2, 13-15, 17, 19-22, and 27 are rejected under 35 U.S.C. 103 as being unpatentable over Suarez et al. (supra) in view of Ying et al. (Nat Med. 2019 Jun;25(6):947-953. doi: 10.1038/s41591-019-0421-7).
The teachings of Suarez et al. are discussed supra.
Suarez et al. does not teach the CAR-T cell expressing an anti-CD19 CAR (i.e., the limitations of instant claim 17).
Ying et al., in the same field of endeavor, teaches the anti-CD19 CAR CD19-BBz (Abstract, Fig. 1):
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Ying et al. further teaches the anti-CD19 CAR-T cells has potent efficacy with lower adverse effects (Table 2, Fig. 3, pg. 950): “…these data demonstrate that CD19-BBz(86) CAR T cell therapy has potent clinical efficacy without causing any neurological toxicity or severe CRS (greater than grade 1).” Ying et al. teaches that the CAR-T therapy comprising this CAR successfully treats lymphoma (Fig. 2).
Ying et al. teaches the anti-CD19 CAR comprises an anti-CD19 scFv, a CD8α TM domain, a 4-1BB costimulatory domain, and a CD3ζ signaling domain (Fig. 1, Methods): “…comprising FMC63 scFv, the extracellular domain and transmembrane regions (71 amino acids) of human CD8α, the cytoplasmic region of human 4-1BB, and the cytoplasmic part of the human CD3ζ molecule…”, which are the limitations of instant claims 17 and 19-22.
It would have been obvious to one with ordinary skill in the art, before the effective filing date of the instant application, to have modified the teachings of Suarez et al. in view of Ying et al. to make the CAR-T cell of Suarez et al. to express the CD19-BBz(86) CAR (i.e., the limitations of instant claims 17 and 19-22) with a reasonable expectation of success, as Ying et al teaches methods of generating such CAR-T cells. One would have been motivated to make this change to engineer the CAR-T cell of Suarez et al. to target treat CD19 expressing cancers such as lymphoma.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Claims 1, 2, 13-15, 20, 25-27, and 46 are rejected under 35 U.S.C. 103 as being unpatentable over Suarez et al. (supra) in view of Johnson et al. (J Immu. 2019 May;202(1):134.4. doi: 10.4049/jimmunol.202.Supp.134.4).
The teachings of Suarez et al. are discussed supra.
Suarez et al. does not teach the CAR-T cell expressing a RNA PRR activator such as 7SL (i.e., the limitations of instant claim 25, 26, and 46).
Johnson et al. in the same field of endeavor, teaches that expression of the RNA 7SL in CAR-T cells, enhances CAR-T efficacy in vivo (Abstract): “…we have developed a CAR T cell capable of producing 7SL in the tumor microenvironment, as well as a fully syngeneic B16 solid tumor model for CAR T cell therapy. Murine 7SL-CAR T cells control tumors more robustly than controls and synergize with ICB. Importantly, this effect is dependent on endogenous T cells, indicating that 7SL-CAR T cells are jump-starting an endogenous polyclonal anti-tumor immune response. In total, this represents a novel insight into the role of PRR signaling in tumors and leverages the findings to create a therapy with potential to serve patients that are currently refractory to CAR-T or ICB therapies alone.”
It would have been obvious to one with ordinary skill in the art, before the effective filing date of the instant application, to have modified the teachings of Suarez et al. in view of Johnson et al. to make the CAR-T cell of Suarez et al. to further express the 7SL RNA (i.e., the limitations of instant claims 25, 26, and 46) with a reasonable expectation of success, as Johnson et al teaches methods of generating such 7SL-CAR-T cells. One would have been motivated to make this change to engineer the CAR-T cell of Suarez et al. to have greater in vivo efficacy.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
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 1, 2, 13, and 27 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-33 of U.S. Patent No. 10,577,417 (Pat ‘417) in view of Suarez et al. (Oncotarget. 2016 Jun 7;7(23):34341-55. doi: 10.18632/oncotarget.9114, supra).
Pat ‘417 claims nucleic acids encoding chimeric antigen receptors comprising an anti-mesothelin antigen binding domain, a TM domain, and a cytoplasmic domain (claim 1). Pat ’417 additionally claims polypeptides encoded by the nucleic acid (claim 20), and cells engineered to express the nucleic acid (claim 25).
Pat ‘417 does not claim cells engineered to express a CAR and a non-natural therapeutic from the same expression construct (i.e., the limitations of instant claim 1).
Suarez et al., in the same field of endeavor, teaches T-cells genetically modified to express a CAR and a PD-L1 antibody (i.e., “a non-natural therapeutic peptide”; the limitations of instant claim 14), wherein the CAR and antibody are expressed on the same construct (Abstract): “…we used a single bicistronic lentiviral vector to develop a new combination immunotherapy that consists of human anti-carbonic anhydrase IX (CAIX)-targeted chimeric antigen receptor (CAR) T cells engineered to secrete human anti-programmed death ligand 1 (PD-L1) antibodies at the tumor site…”
Suarez et al. teaches that the local intratumoral delivery of PD-L1 antibodies can overcome T-cell exhaustion and improve treatment outcomes (pg. 34350): “…CAR T cells secreting anti-PD-L1 IgG1 or IgG4 can diminish T cell exhaustion and improve CAR T cell treatment…”
It would have been obvious to one with ordinary skill in the art to have modified the invention claimed by Pat ‘417 in view of Suarez et al. to engineer cells to express the CAR claimed by Pat ‘417 and PD-L1 antibodies from the same expression construct (i.e., “a non-natural therapeutic peptide”, the limitations of instant claims 1 and 2) because Suarez et al. teaches methods of making such engineered cells. One would have been motivated to make this change for the purposes of engineering the CAR expressing cells claimed by Pat ‘417 to further express anti-PD-L1 antibodies to allow for local intratumoral delivery of these antibodies to overcome T-cell exhaustion and improve antitumor efficacy.
Regarding instant claim 13, Pat ‘417 claims methods of treating MSLN expressing cancers (claim 28), meeting the claim limitations.
Regarding instant claim 27, Suarez et al. teaches compositions comprising the engineered cells in culture medium (“Methods”): “5×104 skrc59 CAIX+/PD-L1+ cells were suspended in 10 μL of culture medium…”, meeting the claim limitations.
Therefore, the invention encompassed by the instant claims is a prima facie obvious variant of the invention claimed by Pat ‘417 in view of Suarez et al., especially in the absence of evidence to the contrary.
Claims 6 and 10 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-33 of U.S. Patent No. 10,577,417 (Pat ‘417) in view of Suarez et al. (supra), as applied to claims 1, 2, 13, and 27, and further in view of Michie et al. (Cancer Immunol Res. 2019 Feb;7(2):183-192. doi: 10.1158/2326-6066.CIR-18-0428, supra) and Bilim et al. (Br J Cancer. 2008 Mar 11;98(5):941-9. doi: 10.1038/sj.bjc.6604268, supra).
The combined teachings of Pat ‘417 in view of Suarez et al. has been discussed supra. The combined references do not teach the CAR expressing cell further expressing a peptide SMAC inhibitor that can be expressed by the CAR-T cell (i.e., the limitations of instant claim 6).
The invention encompassed by the instant claims is a prima facie obvious variant of the invention claimed by Pat ‘417 in view of Suarez et al., and further in view of Michie et al. and Bilim et al. for the same reasons discussed in the 35 U.S.C. § 103 rejection supra, especially in the absence of evidence to the contrary.
Claims 25, 26, and 46 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-33 of U.S. Patent No. 10,577,417 (Pat ‘417) in view of Suarez et al. (supra), as applied to claims 1, 2, 13, and 27, and further in view of Johnson et al. (J Immu. 2019 May;202(1):134.4. doi: 10.4049/jimmunol.202.Supp.134.4, supra).
The combined teachings of Pat ‘417 in view of Suarez et al. has been discussed supra. The combined references do not teach the CAR expressing cell further expressing a RNA PRR activator such as 7SL (i.e., the limitations of instant claims 25, 26, and 46).
The invention encompassed by the instant claims is a prima facie obvious variant of the invention claimed by Pat ‘417 in view of Suarez et al., and further in view of Johnson et al. for the same reasons discussed in the 35 U.S.C. § 103 rejection supra, especially in the absence of evidence to the contrary.
Claims 1, 2, 14, 15, 20, and 27 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of U.S. Patent No. 11,827,705 (Pat ‘705) in view of Suarez et al. (supra).
Pat ‘705 claims a modified T-cell (i.e., the limitations of instant claim 14) comprising a CAR comprising an HLA-A2 antigen binding domain, a CD8 hinge, a CD28 TM domain, and a CD3ζ signaling domain (i.e., the limitations of instant claim 20; Pat ‘705 claims 1 and 2). Pat ‘705 claims the antigen binding domain is an scFv (i.e., the limitations of instant claim 15).
The invention encompassed by the instant claims is a prima facie obvious variant of the invention claimed by Pat ‘705 in view of Suarez et al. for the same reasons discussed for Pat ‘417 supra, especially in the absence of evidence to the contrary.
Claims 6 and 10 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of U.S. Patent No. 11,827,705 (Pat ‘705) in view of Suarez et al. (supra), as applied to claims 1, 2, 14, 15, 20, and 27 and further in view of Michie et al. (supra) and Bilim et al. (supra).
The combined teachings of Pat ‘705 in view of Suarez et al. has been discussed supra. The combined references do not teach the CAR expressing cell further expressing a peptide SMAC inhibitor that can be expressed by the CAR-T cell (i.e., the limitations of instant claim 6).
The invention encompassed by the instant claims is a prima facie obvious variant of the invention claimed by Pat ‘705 in view of Suarez et al., and further in view of Michie et al. and Bilim et al. for the same reasons discussed in the 35 U.S.C. § 103 rejection supra, especially in the absence of evidence to the contrary.
Claims 25, 26, and 46 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of U.S. Patent No. 11,827,705 (Pat ‘705) in view of Suarez et al. (supra), as applied to claims 1, 2, 14, 15, 20, and 27, and further in view of Johnson et al. (supra).
The combined teachings of Pat ‘705 in view of Suarez et al. has been discussed supra. The combined references do not teach the CAR expressing cell further expressing a RNA PRR activator such as 7SL (i.e., the limitations of instant claims 25, 26, and 46).
The invention encompassed by the instant claims is a prima facie obvious variant of the invention claimed by Pat ‘417 in view of Suarez et al., and further in view of Johnson et al. for the same reasons discussed in the 35 U.S.C. § 103 rejection supra, especially in the absence of evidence to the contrary.
Claims 1, 2, 13-15, 17, 19-22 and 27 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-46 of U.S. Patent No. 12,128,069 (Pat ‘069) in view of Suarez et al. (supra).
Pat ‘069 claims a nucleic acid encoding a chimeric antigen receptor comprising an antigen binding domain, a TM domain, an ICD domain, and a costimulatory domain (claims 1 and 10). Pat ‘069 claims cells expressing the nucleic acid (claim 32).
Pat ‘069 additionally claims the cell can be a T-cell (i.e., the limitations of instant claim 14; Pat ‘069 claim 33), the antigen binding domain is an scFv (i.e., the limitations of instant claim 15; Pat ‘069 claim 16), the antigen is a tumor associated CD19 (i.e., the limitations of instant claims 13 and 17; Pat ‘069 claim 11 and 12), a CD8 TM domain (i.e., the limitations of instant claim 19; Pat ‘069 claim 17), a CD3ζ ICD (i.e., the limitations of instant claim 20; Pat ‘069 claim 14), a 4-1BB costimulatory domain (i.e., the limitations of instant claims 21 and 22; Pat ‘069 claim 15)
The invention encompassed by the instant claims is a prima facie obvious variant of the invention claimed by Pat ‘069 in view of Suarez et al. for the same reasons discussed for Pat ‘417 supra, especially in the absence of evidence to the contrary.
Claims 6 and 10 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-46 of U.S. Patent No. 12,128,069 (Pat ‘069) in view of Suarez et al. (supra), as applied to claims 1, 2, 13-15, 17, 19-22 and 27 and further in view of Michie et al. (supra) and Bilim et al. (supra).
The combined teachings of Pat ‘069 in view of Suarez et al. has been discussed supra. The combined references do not teach the CAR expressing cell further expressing a peptide SMAC inhibitor that can be expressed by the CAR-T cell (i.e., the limitations of instant claim 6).
The invention encompassed by the instant claims is a prima facie obvious variant of the invention claimed by Pat ‘069 in view of Suarez et al., and further in view of Michie et al. and Bilim et al. for the same reasons discussed in the 35 U.S.C. § 103 rejection supra, especially in the absence of evidence to the contrary.
Claims 25, 26, and 46 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-46 of U.S. Patent No. 12,128,069 (Pat ‘069) in view of Suarez et al. (supra), as applied to claims 1, 2, 13-15, 17, 19-22 and 27 and further in view of Johnson et al. (supra).
The combined teachings of Pat ‘069 in view of Suarez et al. has been discussed supra. The combined references do not teach the CAR expressing cell further expressing a RNA PRR activator such as 7SL (i.e., the limitations of instant claims 25, 26, and 46).
The invention encompassed by the instant claims is a prima facie obvious variant of the invention claimed by Pat ‘417 in view of Suarez et al., and further in view of Johnson et al. for the same reasons discussed in the 35 U.S.C. § 103 rejection supra, especially in the absence of evidence to the contrary.
Claims 1, 2, 13-15, 17, 19-22 and 27 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-34 of U.S. Patent No. RE49,847 (Pat ‘847) in view of Suarez et al. (supra).
Pat ‘847 claims a nucleic acid encoding a chimeric antigen receptor comprising an antigen binding domain, a TM domain, an ICD domain, and a costimulatory domain (claims 1 and 10). Pat ‘847 claims cells expressing the nucleic acid (claims 30 and 31).
Pat ‘847 additionally claims the cell can be a T-cell (i.e., the limitations of instant claim 14; Pat ‘847 claim 28), the antigen binding domain is an scFv (i.e., the limitations of instant claim 15; Pat ‘847 claim 23(ii)), the antigen is a tumor associated CD19 (i.e., the limitations of instant claims 13 and 17; Pat ‘847 claim 19 and 22), a CD8 TM domain (i.e., the limitations of instant claim 19; Pat ‘847 claim 6), a CD3ζ ICD (i.e., the limitations of instant claim 20; Pat ‘847 claim 14), a 4-1BB costimulatory domain (i.e., the limitations of instant claims 21 and 22; Pat ‘847 claim 14).
The invention encompassed by the instant claims is a prima facie obvious variant of the invention claimed by Pat ‘847 in view of Suarez et al. for the same reasons discussed for Pat ‘417 supra, especially in the absence of evidence to the contrary.
Claims 6 and 10 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-34 of U.S. Patent No. RE49,847 (Pat ‘847) in view of Suarez et al. (supra), as applied to claims 1, 2, 13-15, 17, 19-22 and 27 above, and further in view of Michie et al. (supra) and Bilim et al. (supra).
The combined teachings of Pat ‘847 in view of Suarez et al. has been discussed supra. The combined references do not teach the CAR expressing cell further expressing a peptide SMAC inhibitor that can be expressed by the CAR-T cell (i.e., the limitations of instant claim 6).
The invention encompassed by the instant claims is a prima facie obvious variant of the invention claimed by Pat ‘847 in view of Suarez et al., and further in view of Michie et al. and Bilim et al. for the same reasons discussed in the 35 U.S.C. § 103 rejection supra, especially in the absence of evidence to the contrary.
Claims 25, 26, and 46 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-34 of U.S. Patent No. RE49,847 (Pat ‘847) in view of Suarez et al. (supra), as applied to claims 1, 2, 13-15, 17, 19-22 and 27 and further in view of Johnson et al. (supra).
The combined teachings of Pat ‘847 in view of Suarez et al. has been discussed supra. The combined references do not teach the CAR expressing cell further expressing a RNA PRR activator such as 7SL (i.e., the limitations of instant claims 25, 26, and 46).
The invention encompassed by the instant claims is a prima facie obvious variant of the invention claimed by Pat ‘417 in view of Suarez et al., and further in view of Johnson et al. for the same reasons discussed in the 35 U.S.C. § 103 rejection supra, especially in the absence of evidence to the contrary.
Claims 1, 2, 13-15, 17, 19-22 and 27 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-38 of U.S. Patent No. 11,872,249 (Pat ‘249) in view of Suarez et al. (supra).
Pat ‘249 claims methods of using engineered cells expressing a nucleic acid encoding a chimeric antigen receptor comprising an antigen binding domain, a TM domain, an ICD domain, and a costimulatory domain (claim 1).
Pat ‘249 additionally claims the cell can be a T-cell (i.e., the limitations of instant claim 14; Pat ‘249 claim 1), the antigen binding domain is an scFv (i.e., the limitations of instant claim 15; Pat ‘249 claim 12), the antigen is a tumor associated CD19 (i.e., the limitations of instant claims 13 and 17; Pat ‘249 claims 2, 25, and 26), a CD8 TM domain (i.e., the limitations of instant claim 19; Pat ‘249 claim 14), a CD3ζ ICD (i.e., the limitations of instant claim 20; Pat ‘249 claim 19), a 4-1BB costimulatory domain (i.e., the limitations of instant claims 21 and 22; Pat ‘249 claim 17).
The invention encompassed by the instant claims is a prima facie obvious variant of the invention claimed by Pat ‘249 in view of Suarez et al. for the same reasons discussed for Pat ‘417 supra, especially in the absence of evidence to the contrary.
Claims 6 and 10 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-38 of U.S. Patent No. 11,872,249 (Pat ‘249) in view of Suarez et al. (supra), as applied to claims 1, 2, 13-15, 17, 19-22 and 27 above, and further in view of Michie et al. (supra) and Bilim et al. (supra).
The combined teachings of Pat ‘249 in view of Suarez et al. has been discussed supra. The combined references do not teach the CAR expressing cell further expressing a peptide SMAC inhibitor that can be expressed by the CAR-T cell (i.e., the limitations of instant claim 6).
The invention encompassed by the instant claims is a prima facie obvious variant of the invention claimed by Pat ‘249 in view of Suarez et al., and further in view of Michie et al. and Bilim et al. for the same reasons discussed in the 35 U.S.C. § 103 rejection supra, especially in the absence of evidence to the contrary.
Claims 25, 26, and 46 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-38 of U.S. Patent No. 11,872,249 (Pat ‘249) in view of Suarez et al. (supra), as applied to claims 1, 2, 13-15, 17, 19-22 and 27 above, and further in view of Johnson et al. (supra).
The combined teachings of Pat ‘249 in view of Suarez et al. has been discussed supra. The combined references do not teach the CAR expressing cell further expressing a RNA PRR activator such as 7SL (i.e., the limitations of instant claims 25, 26, and 46).
The invention encompassed by the instant claims is a prima facie obvious variant of the invention claimed by Pat ‘417 in view of Suarez et al., and further in view of Johnson et al. for the same reasons discussed in the 35 U.S.C. § 103 rejection supra, especially in the absence of evidence to the contrary.
Claims 1, 2, 13-15, 17, 19-22 and 27 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-33 of U.S. Patent No. 10,525,083 (Pat ‘083) in view of Suarez et al. (supra).
Pat ‘083 claims a nucleic acid encoding a chimeric antigen receptor comprising an antigen binding domain, a TM domain, an ICD domain, and a costimulatory domain (claim 1). Pat ‘083 claims cells expressing the nucleic acid (claim 30 and 31).
Pat ‘083 additionally claims the cell can be a T-cell (i.e., the limitations of instant claim 14; Pat ‘083 claim 28), the antigen binding domain is an scFv (i.e., the limitations of instant claim 15; Pat ‘083 claim 4), the antigen is a tumor associated CD19 (i.e., the limitations of instant claims 13 and 17; Pat ‘083 claims 23), a CD8 TM domain (i.e., the limitations of instant claim 19; Pat ‘083 claim 6), a CD3ζ ICD (i.e., the limitations of instant claim 20; Pat ‘083 claim 12), a 4-1BB costimulatory domain (i.e., the limitations of instant claims 21 and 22; Pat ‘083 claim 14).
The invention encompassed by the instant claims is a prima facie obvious variant of the invention claimed by Pat ‘083 in view of Suarez et al. for the same reasons discussed for Pat ‘417 supra, especially in the absence of evidence to the contrary.
Claims 6 and 10 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-33 of U.S. Patent No. 10,525,083 (Pat ‘083) in view of Suarez et al. (supra), as applied to claims 1, 2, 13-15, 17, 19-22 and 27 above, and further in view of Michie et al. (supra) and Bilim et al. (supra).
The combined teachings of Pat ‘083 in view of Suarez et al. has been discussed supra. The combined references do not teach the CAR expressing cell further expressing a peptide SMAC inhibitor that can be expressed by the CAR-T cell (i.e., the limitations of instant claim 6).
The invention encompassed by the instant claims is a prima facie obvious variant of the invention claimed by Pat ‘083 in view of Suarez et al., and further in view of Michie et al. and Bilim et al. for the same reasons discussed in the 35 U.S.C. § 103 rejection supra, especially in the absence of evidence to the contrary.
Claims 25, 26, and 46 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-33 of U.S. Patent No. 10,525,083 (Pat ‘083) in view of Suarez et al. (supra), as applied to claims 1, 2, 13-15, 17, 19-22 and 27 above, and further in view of Johnson et al. (supra).
The combined teachings of Pat ‘083 in view of Suarez et al. has been discussed supra. The combined references do not teach the CAR expressing cell further expressing a RNA PRR activator such as 7SL (i.e., the limitations of instant claims 25, 26, and 46).
The invention encompassed by the instant claims is a prima facie obvious variant of the invention claimed by Pat ‘083 in view of Suarez et al., and further in view of Johnson et al. for the same reasons discussed in the 35 U.S.C. § 103 rejection supra, especially in the absence of evidence to the contrary.
Claims 1, 2, 14, 15, 19, 20, and 27 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of U.S. Patent No. 12,215,154 (Pat ‘154) in view of Suarez et al. (supra).
Pat ‘154 claims a nucleic acid encoding a chimeric antigen receptor comprising an antigen binding domain, a TM domain, an ICD domain, and a costimulatory domain (claim 1). Pat ‘154 claims cells expressing the nucleic acid (claim 13).
Pat ‘154 additionally claims the cell can be a T-cell (i.e., the limitations of instant claim 14; Pat ‘154 claim 16), the antigen binding domain is an scFv (i.e., the limitations of instant claim 15; Pat ‘154 claims 1 and 13, SEQ ID NO: 1 of Pat ‘154 comprises a scFv), a CD8 TM domain (i.e., the limitations of instant claim 19; Pat ‘154 claim 5), a CD3ζ ICD (i.e., the limitations of instant claim 20; Pat ‘154 claim 8).
The invention encompassed by the instant claims is a prima facie obvious variant of the invention claimed by Pat ‘154 in view of Suarez et al. for the same reasons discussed for Pat ‘417 supra, especially in the absence of evidence to the contrary.
Claims 6 and 10 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of U.S. Patent No. 12,215,154 (Pat ‘154) in view of Suarez et al. (supra), as applied to claims 1, 2, 14, 15, 19, 20, and 27 above, and further in view of Michie et al. (supra) and Bilim et al. (supra).
The combined teachings of Pat ‘154 in view of Suarez et al. has been discussed supra. The combined references do not teach the CAR expressing cell further expressing a peptide SMAC inhibitor that can be expressed by the CAR-T cell (i.e., the limitations of instant claim 6).
The invention encompassed by the instant claims is a prima facie obvious variant of the invention claimed by Pat ‘154 in view of Suarez et al., and further in view of Michie et al. and Bilim et al. for the same reasons discussed in the 35 U.S.C. § 103 rejection supra, especially in the absence of evidence to the contrary.
Claims 25, 26, and 46 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of U.S. Patent No. 12,215,154 (Pat ‘154) in view of Suarez et al. (supra), as applied to claims 1, 2, 14, 15, 19, 20, and 27 above, and further in view of Johnson et al. (supra).
The combined teachings of Pat ‘154 in view of Suarez et al. has been discussed supra. The combined references do not teach the CAR expressing cell further expressing a RNA PRR activator such as 7SL (i.e., the limitations of instant claims 25, 26, and 46).
The invention encompassed by the instant claims is a prima facie obvious variant of the invention claimed by Pat ‘417 in view of Suarez et al., and further in view of Johnson et al. for the same reasons discussed in the 35 U.S.C. § 103 rejection supra, especially in the absence of evidence to the contrary.
Claims 1, 2, 13, 14, 19-22 and 27 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No. 12,410,234 (Pat ‘234) in view of Suarez et al. (supra).
Pat ‘234 claims a chimeric antigen receptor comprising an antigen binding domain, a TM domain, an ICD domain, and a costimulatory domain (claim 1). Pat ‘234 claims cells expressing the CAR (claim 12).
Pat ‘234 additionally claims the cell can be a T-cell (i.e., the limitations of instant claim 14; Pat ‘234 claim 12), the antigen is a tumor associated CDH17 (i.e., the limitations of instant claim 13; Pat ‘234 claim 14), a CD8 TM domain (i.e., the limitations of instant claim 19; Pat ‘234 claim 6), a CD3ζ ICD (i.e., the limitations of instant claim 20; Pat ‘234 claim 8), a 4-1BB costimulatory domain (i.e., the limitations of instant claims 21 and 22; Pat ‘234 claim 8).
The invention encompassed by the instant claims is a prima facie obvious variant of the invention claimed by Pat ‘234 in view of Suarez et al. for the same reasons discussed for Pat ‘417 supra, especially in the absence of evidence to the contrary.
Claims 6 and 10 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No. 12,410,234 (Pat ‘234) in view of Suarez et al. (supra), as applied to claims 1, 2, 13, 14, 19-22 and 27 above, and further in view of Michie et al. (supra) and Bilim et al. (supra).
The combined teachings of Pat ‘234 in view of Suarez et al. has been discussed supra. The combined references do not teach the CAR expressing cell further expressing a peptide SMAC inhibitor that can be expressed by the CAR-T cell (i.e., the limitations of instant claim 6).
The invention encompassed by the instant claims is a prima facie obvious variant of the invention claimed by Pat ‘234 in view of Suarez et al., and further in view of Michie et al. and Bilim et al. for the same reasons discussed in the 35 U.S.C. § 103 rejection supra, especially in the absence of evidence to the contrary.
Claims 25, 26, and 46 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No. 12,410,234 (Pat ‘234) in view of Suarez et al. (supra), as applied to claims 1, 2, 13, 14, 19-22 and 27 above, and further in view of Johnson et al. (supra).
The combined teachings of Pat ‘234 in view of Suarez et al. has been discussed supra. The combined references do not teach the CAR expressing cell further expressing a RNA PRR activator such as 7SL (i.e., the limitations of instant claims 25, 26, and 46).
The invention encompassed by the instant claims is a prima facie obvious variant of the invention claimed by Pat ‘417 in view of Suarez et al., and further in view of Johnson et al. for the same reasons discussed in the 35 U.S.C. § 103 rejection supra, especially in the absence of evidence to the contrary.
Claims 1, 2, 13, 14, 17, 20-22 and 27 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-21 of U.S. Patent No. 11,459,390 (Pat ‘390) in view of Suarez et al. (supra).
Pat ‘390 claims a nucleic acid encoding a chimeric antigen receptor comprising an antigen binding domain, a TM domain, an ICD domain, and a costimulatory domain (claim 1). Pat ‘390 claims cells expressing the nucleic acid (claim 9).
Pat ‘390 additionally claims the cell can be a T-cell (i.e., the limitations of instant claim 14; Pat ‘390 claim 10), the antigen is a tumor associated CD19 (i.e., the limitations of instant claims 13 and 17; Pat ‘390 claims 2), a CD3ζ ICD (i.e., the limitations of instant claim 20; Pat ‘390 claim 6), a 4-1BB costimulatory domain (i.e., the limitations of instant claims 21 and 22; Pat ‘390 claim 6).
The invention encompassed by the instant claims is a prima facie obvious variant of the invention claimed by Pat ‘390 in view of Suarez et al. for the same reasons discussed for Pat ‘417 supra, especially in the absence of evidence to the contrary.
Claims 6 and 10 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-21 of U.S. Patent No. 11,459,390 (Pat ‘390) in view of Suarez et al. (supra), as applied to claims 1, 2, 13, 14, 17, 20-22 and 27 above, and further in view of Michie et al. (supra) and Bilim et al. (supra).
The combined teachings of Pat ‘390 in view of Suarez et al. has been discussed supra. The combined references do not teach the CAR expressing cell further expressing a peptide SMAC inhibitor that can be expressed by the CAR-T cell (i.e., the limitations of instant claim 6).
The invention encompassed by the instant claims is a prima facie obvious variant of the invention claimed by Pat ‘390 in view of Suarez et al., and further in view of Michie et al. and Bilim et al. for the same reasons discussed in the 35 U.S.C. § 103 rejection supra, especially in the absence of evidence to the contrary.
Claims 25, 26, and 46 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-21 of U.S. Patent No. 11,459,390 (Pat ‘390) in view of Suarez et al. (supra), as applied to claims 1, 2, 13, 14, 17, 20-22 and 27 above, and further in view of Johnson et al. (supra).
The combined teachings of Pat ‘390 in view of Suarez et al. has been discussed supra. The combined references do not teach the CAR expressing cell further expressing a RNA PRR activator such as 7SL (i.e., the limitations of instant claims 25, 26, and 46).
The invention encompassed by the instant claims is a prima facie obvious variant of the invention claimed by Pat ‘417 in view of Suarez et al., and further in view of Johnson et al. for the same reasons discussed in the 35 U.S.C. § 103 rejection supra, especially in the absence of evidence to the contrary.
Claims 1, 2, 14, 15, 20-22 and 27 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of U.S. Patent No. 12,383,581 (Pat ‘581) in view of Suarez et al. (supra).
Pat ‘581 claims CARs comprising an antigen binding domain, a TM domain, an ICD domain, and a costimulatory domain (claim 1), as well as modified cells expressing the CAR (claim 11).
Pat ‘581 additionally claims the cell can be a T-cell (i.e., the limitations of instant claim 14; Pat ‘581 claims 11 and 12), the antigen binding domain is an scFv (i.e., the limitations of instant claim 15; Pat ‘581 claim 2), a CD3ζ ICD (i.e., the limitations of instant claim 20; Pat ‘581 claim 7), a 4-1BB costimulatory domain (i.e., the limitations of instant claims 21 and 22; Pat ‘581 claim 8).
The invention encompassed by the instant claims is a prima facie obvious variant of the invention claimed by Pat ‘581 in view of Suarez et al. for the same reasons discussed for Pat ‘417 supra, especially in the absence of evidence to the contrary.
Claims 6 and 10 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of U.S. Patent No. 12,383,581 (Pat ‘581) in view of Suarez et al. (supra), as applied to claims 1, 2, 14, 15, 20-22 and 27 above, and further in view of Michie et al. (supra) and Bilim et al. (supra).
The combined teachings of Pat ‘581 in view of Suarez et al. has been discussed supra. The combined references do not teach the CAR expressing cell further expressing a peptide SMAC inhibitor that can be expressed by the CAR-T cell (i.e., the limitations of instant claim 6).
The invention encompassed by the instant claims is a prima facie obvious variant of the invention claimed by Pat ‘581 in view of Suarez et al., and further in view of Michie et al. and Bilim et al. for the same reasons discussed in the 35 U.S.C. § 103 rejection supra, especially in the absence of evidence to the contrary.
Claims 25, 26, and 46 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of U.S. Patent No. 12,383,581 (Pat ‘581) in view of Suarez et al. (supra), as applied to claims 1, 2, 14, 15, 20-22 and 27 above, and further in view of Johnson et al. (supra).
The combined teachings of Pat ‘581 in view of Suarez et al. has been discussed supra. The combined references do not teach the CAR expressing cell further expressing a RNA PRR activator such as 7SL (i.e., the limitations of instant claims 25, 26, and 46).
The invention encompassed by the instant claims is a prima facie obvious variant of the invention claimed by Pat ‘417 in view of Suarez et al., and further in view of Johnson et al. for the same reasons discussed in the 35 U.S.C. § 103 rejection supra, especially in the absence of evidence to the contrary.
Claims 1, 2, 13, 15, 17, 20-22 and 27 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 6, 16, 33, 37, 43, 46, 50, 54, 64, 65, 69, 70, 73-75, 77, 87, 90, 93, 99, 104, 111, 112, 167-182 of copending Application No. 16/093,758 (App ‘758) in view of Suarez et al. (supra).
App ‘758 claims CARs comprising chimeric antigen receptor comprising an antigen binding domain, a TM domain, and an ICD domain (claim 1), as well as cells expressing the CAR (claim 74).
App ‘758 additionally claims the antigen binding domain is an scFv (i.e., the limitations of instant claim 15; App ‘758 claim 50), the antigen is a tumor associated CD19 (i.e., the limitations of instant claims 13 and 17; App ‘758 claim 174), a CD3ζ ICD (i.e., the limitations of instant claim 20; App ‘758 claim 46), a 4-1BB costimulatory domain (i.e., the limitations of instant claims 21 and 22; App ‘758 claim 46).
The invention encompassed by the instant claims is a prima facie obvious variant of the invention claimed by App ‘758 in view of Suarez et al. for the same reasons discussed for Pat ‘417 supra, especially in the absence of evidence to the contrary. This is a provisional double patenting rejection.
Claims 6 and 10 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 6, 16, 33, 37, 43, 46, 50, 54, 64, 65, 69, 70, 73-75, 77, 87, 90, 93, 99, 104, 111, 112, 167-182 of copending Application No. 16/093,758 (App ‘758) in view of Suarez et al. (supra), as applied to claims 1, 2, 13, 15, 17, 20-22 and 27 above, and further in view of Michie et al. (supra) and Bilim et al. (supra).
The combined teachings of App ‘758 in view of Suarez et al. has been discussed supra. The combined references do not teach the CAR expressing cell further expressing a peptide SMAC inhibitor that can be expressed by the CAR-T cell (i.e., the limitations of instant claim 6).
The invention encompassed by the instant claims is a prima facie obvious variant of the invention claimed by App ‘758 in view of Suarez et al., and further in view of Michie et al. and Bilim et al. for the same reasons discussed in the 35 U.S.C. § 103 rejection supra, especially in the absence of evidence to the contrary. This is a provisional double patenting rejection.
Claims 25, 26, and 46 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 6, 16, 33, 37, 43, 46, 50, 54, 64, 65, 69, 70, 73-75, 77, 87, 90, 93, 99, 104, 111, 112, 167-182 of copending Application No. 16/093,758 (App ‘758) in view of Suarez et al. (supra), as applied to claims 1, 2, 13, 15, 17, 20-22 and 27 above, and further in view of Johnson et al. (supra).
The combined teachings of App ‘758 in view of Suarez et al. has been discussed supra. The combined references do not teach the CAR expressing cell further expressing a RNA PRR activator such as 7SL (i.e., the limitations of instant claims 25, 26, and 46).
The invention encompassed by the instant claims is a prima facie obvious variant of the invention claimed by Pat ‘417 in view of Suarez et al., and further in view of Johnson et al. for the same reasons discussed in the 35 U.S.C. § 103 rejection supra, especially in the absence of evidence to the contrary. This is a provisional double patenting rejection.
Claims 1, 2, 13-15, 19-21 and 27 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 2, 3, 7-11, 14, 15, 20, 27, 31, 35-38, 44, and 57-59 of copending Application No. 16/965,880 (App ‘880) in view of Suarez et al. (supra).
App ‘880 claims CARs comprising chimeric antigen receptor comprising an antigen binding domain, a TM domain, an ICD domain (claims 2 and 57).
App ‘880 additionally claims the cell can be a T-cell (i.e., the limitations of instant claim 14; App ‘880 claim44(xiii)), the antigen binding domain is an scFv (i.e., the limitations of instant claim 15; App ‘880 claim 31(iv)), the antigen is a tumor associated mesothelin (i.e., the limitations of instant claim 13; App ‘880 claims 2), a CD8 TM domain (i.e., the limitations of instant claim 19; App ‘880 claim 38(ii)), a CD3ζ ICD (i.e., the limitations of instant claim 20; App ‘880 claim 38(iii)), a 4-1BB costimulatory domain (i.e., the limitations of instant claim 21; App ‘880 claim 38(x)).
The invention encompassed by the instant claims is a prima facie obvious variant of the invention claimed by App ‘880 in view of Suarez et al. for the same reasons discussed for Pat ‘417 supra, especially in the absence of evidence to the contrary. This is a provisional double patenting rejection.
Claims 6 and 10 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 2, 3, 7-11, 14, 15, 20, 27, 31, 35-38, 44, and 57-59 of copending Application No. 16/965,880 (App ‘880) in view of Suarez et al. (supra), as applied to claims 1, 2, 13-15, 19-21 and 27 above, and further in view of Michie et al. (supra) and Bilim et al. (supra).
The combined teachings of App ‘880 in view of Suarez et al. has been discussed supra. The combined references do not teach the CAR expressing cell further expressing a peptide SMAC inhibitor that can be expressed by the CAR-T cell (i.e., the limitations of instant claim 6).
The invention encompassed by the instant claims is a prima facie obvious variant of the invention claimed by App ‘880 in view of Suarez et al., and further in view of Michie et al. and Bilim et al. for the same reasons discussed in the 35 U.S.C. § 103 rejection supra, especially in the absence of evidence to the contrary. This is a provisional double patenting rejection.
Claims 25, 26, and 46 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 2, 3, 7-11, 14, 15, 20, 27, 31, 35-38, 44, and 57-59 of copending Application No. 16/965,880 (App ‘880) in view of Suarez et al. (supra), as applied to claims 1, 2, 13-15, 19-21 and 27 above, and further in view of Johnson et al. (supra).
The combined teachings of App ‘880 in view of Suarez et al. has been discussed supra. The combined references do not teach the CAR expressing cell further expressing a RNA PRR activator such as 7SL (i.e., the limitations of instant claims 25, 26, and 46).
The invention encompassed by the instant claims is a prima facie obvious variant of the invention claimed by Pat ‘417 in view of Suarez et al., and further in view of Johnson et al. for the same reasons discussed in the 35 U.S.C. § 103 rejection supra, especially in the absence of evidence to the contrary. This is a provisional double patenting rejection.
Claims 1, 2, 13-15, 19-21 and 27 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-23, 25-50, and 52-58 of copending Application No. 17/047,993 (App ‘993) in view of Suarez et al. (supra).
App ‘993 claims nucleic acids encoding CARs comprising chimeric antigen receptor comprising an antigen binding domain, a TM domain, an ICD domain (claim 1), and cells expressing the CAR (claim 18).
App ‘993 additionally claims the cell can be a T-cell (i.e., the limitations of instant claim 14; App ‘993 claim 22), the antigen is a tumor associated MCR (i.e., the limitations of instant claim 13; App ‘993 claim 24), a CD8 TM domain (i.e., the limitations of instant claim 19; App ‘993 claim 4), a CD3ζ ICD (i.e., the limitations of instant claim 20; App ‘993 claim 5), a 4-1BB costimulatory domain (i.e., the limitations of instant claim 21; App ‘993 claim 6).
The invention encompassed by the instant claims is a prima facie obvious variant of the invention claimed by App ‘993 in view of Suarez et al. for the same reasons discussed for Pat ‘417 supra, especially in the absence of evidence to the contrary. This is a provisional double patenting rejection.
Claims 6 and 10 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-23, 25-50, and 52-58 of copending Application No. 17/047,993 (App ‘993) in view of Suarez et al. (supra), as applied to claims 1, 2, 13-15, 19-21 and 27 above, and further in view of Michie et al. (supra) and Bilim et al. (supra).
The combined teachings of App ‘993 in view of Suarez et al. has been discussed supra. The combined references do not teach the CAR expressing cell further expressing a peptide SMAC inhibitor that can be expressed by the CAR-T cell (i.e., the limitations of instant claim 6).
The invention encompassed by the instant claims is a prima facie obvious variant of the invention claimed by App ‘993 in view of Suarez et al., and further in view of Michie et al. and Bilim et al. for the same reasons discussed in the 35 U.S.C. § 103 rejection supra, especially in the absence of evidence to the contrary. This is a provisional double patenting rejection.
Claims 25, 26, and 46 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-23, 25-50, and 52-58 of copending Application No. 17/047,993 (App ‘993) in view of Suarez et al. (supra), as applied to claims 1, 2, 13-15, 19-21 and 27 above, and further in view of Johnson et al. (supra).
The combined teachings of App ‘993 in view of Suarez et al. has been discussed supra. The combined references do not teach the CAR expressing cell further expressing a RNA PRR activator such as 7SL (i.e., the limitations of instant claims 25, 26, and 46).
The invention encompassed by the instant claims is a prima facie obvious variant of the invention claimed by Pat ‘417 in view of Suarez et al., and further in view of Johnson et al. for the same reasons discussed in the 35 U.S.C. § 103 rejection supra, especially in the absence of evidence to the contrary. This is a provisional double patenting rejection.
Claims 1, 2, 13-15, 19-21 and 27 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-38 of copending Application No. 17/370,655 (App ‘655) in view of Suarez et al. (supra).
App ‘655 claims modified immune cells expressing a CAR comprising chimeric antigen receptor comprising an antigen binding domain, a TM domain, an ICD domain, and a costimulatory domain (claim 1).
App ‘655 additionally claims the cell can be a T-cell (i.e., the limitations of instant claim 14; App ‘655 claim 7), the antigen binding domain is an scFv (i.e., the limitations of instant claim 15; App ‘655 claim 1, SEQ ID NO: 4 is an scFv), the antigen is a tumor associated MUC1 (i.e., the limitations of instant claim 13; App ‘655 claims 1 and 2), a CD8 TM domain (i.e., the limitations of instant claim 19; App ‘655 claim 5), a CD3ζ ICD (i.e., the limitations of instant claim 20; App ‘655 claim 1), a 4-1BB costimulatory domain (i.e., the limitations of instant claim 21; App ‘655 claim 24).
The invention encompassed by the instant claims is a prima facie obvious variant of the invention claimed by App ‘655 in view of Suarez et al. for the same reasons discussed for Pat ‘417 supra, especially in the absence of evidence to the contrary. This is a provisional double patenting rejection.
Claims 6 and 10 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-38 of copending Application No. 17/370,655 (App ‘655) in view of Suarez et al. (supra), as applied to claims 1, 2, 13-15, 19-21 and 27 above, and further in view of Michie et al. (supra) and Bilim et al. (supra).
The combined teachings of App ‘655 in view of Suarez et al. has been discussed supra. The combined references do not teach the CAR expressing cell further expressing a peptide SMAC inhibitor that can be expressed by the CAR-T cell (i.e., the limitations of instant claim 6).
The invention encompassed by the instant claims is a prima facie obvious variant of the invention claimed by App ‘655 in view of Suarez et al., and further in view of Michie et al. and Bilim et al. for the same reasons discussed in the 35 U.S.C. § 103 rejection supra, especially in the absence of evidence to the contrary. This is a provisional double patenting rejection.
Claims 25, 26, and 46 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-38 of copending Application No. 17/370,655 (App ‘655) in view of Suarez et al. (supra), as applied to claims 1, 2, 13-15, 19-21 and 27 above, and further in view of Johnson et al. (supra).
The combined teachings of App ‘655 in view of Suarez et al. has been discussed supra. The combined references do not teach the CAR expressing cell further expressing a RNA PRR activator such as 7SL (i.e., the limitations of instant claims 25, 26, and 46).
The invention encompassed by the instant claims is a prima facie obvious variant of the invention claimed by Pat ‘417 in view of Suarez et al., and further in view of Johnson et al. for the same reasons discussed in the 35 U.S.C. § 103 rejection supra, especially in the absence of evidence to the contrary. This is a provisional double patenting rejection.
Claims 1, 2, 13-15, 17, 19-22 and 27 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 21, 25, 26, 28, 33, 34, 42, 59, 79, 82, 91, 94, 95, 121, 135, 137, and 145 of copending Application No. 17/441,576 (App ‘576) in view of Suarez et al. (supra).
App ‘576 claims modified immune cells expressing a CAR comprising chimeric antigen receptor comprising an antigen binding domain, a TM domain, an ICD domain, and a costimulatory domain (claims 1 and 121).
App ‘576 additionally claims the cell can be a T-cell (i.e., the limitations of instant claim 14; App ‘576 claim 132), the antigen binding domain is an scFv (i.e., the limitations of instant claim 15; App ‘576 claim 121), the antigen is a tumor associated CD19 (i.e., the limitations of instant claims 13 and 17; App ‘576 claims 121), a CD8 TM domain (i.e., the limitations of instant claim 19; App ‘576 claim 121), a CD3ζ ICD (i.e., the limitations of instant claim 20; App ‘576 claim 121), a 4-1BB costimulatory domain (i.e., the limitations of instant claims 21 and 22; App ‘576 claim 121).
The invention encompassed by the instant claims is a prima facie obvious variant of the invention claimed by App ‘576 in view of Suarez et al. for the same reasons discussed for Pat ‘417 supra, especially in the absence of evidence to the contrary. This is a provisional double patenting rejection.
Claims 6 and 10 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 21, 25, 26, 28, 33, 34, 42, 59, 79, 82, 91, 94, 95, 121, 135, 137, and 145 of copending Application No. 17/441,576 (App ‘576) in view of Suarez et al. (supra), as applied to claims 1, 2, 13-15, 17, 19-22 and 27 above, and further in view of Michie et al. (supra) and Bilim et al. (supra).
The combined teachings of App ‘576 in view of Suarez et al. has been discussed supra. The combined references do not teach the CAR expressing cell further expressing a peptide SMAC inhibitor that can be expressed by the CAR-T cell (i.e., the limitations of instant claim 6).
The invention encompassed by the instant claims is a prima facie obvious variant of the invention claimed by App ‘576 in view of Suarez et al., and further in view of Michie et al. and Bilim et al. for the same reasons discussed in the 35 U.S.C. § 103 rejection supra, especially in the absence of evidence to the contrary. This is a provisional double patenting rejection.
Claims 25, 26, and 46 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 21, 25, 26, 28, 33, 34, 42, 59, 79, 82, 91, 94, 95, 121, 135, 137, and 145 of copending Application No. 17/441,576 (App ‘576) in view of Suarez et al. (supra), as applied to claims 1, 2, 13-15, 17, 19-22 and 27 above, and further in view of Johnson et al. (supra).
The combined teachings of App ‘576 in view of Suarez et al. has been discussed supra. The combined references do not teach the CAR expressing cell further expressing a RNA PRR activator such as 7SL (i.e., the limitations of instant claims 25, 26, and 46).
The invention encompassed by the instant claims is a prima facie obvious variant of the invention claimed by Pat ‘417 in view of Suarez et al., and further in view of Johnson et al. for the same reasons discussed in the 35 U.S.C. § 103 rejection supra, especially in the absence of evidence to the contrary. This is a provisional double patenting rejection.
Claims 1, 2, 13-15, 17, 19-22 and 27 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 21-57 of copending Application No. 18/381,258 (App ‘258) in view of Suarez et al. (supra).
App ‘258 claims nucleic acid encoding a CAR comprising chimeric antigen receptor comprising an antigen binding domain, a TM domain, an ICD domain, and a costimulatory domain (claim 1), as well as cells expressing the nucleic acid (claim 34).
App ‘258 additionally claims the cell can be a T-cell (i.e., the limitations of instant claim 14; App ‘258 claim 34), the antigen binding domain is an scFv (i.e., the limitations of instant claim 15; App ‘258 claim 21), the antigen is a tumor associated CD19 (i.e., the limitations of instant claims 13 and 17; App ‘258 claims 21), a CD8 TM domain (i.e., the limitations of instant claim 19; App ‘258 claim 32), a CD3ζ ICD (i.e., the limitations of instant claim 20; App ‘258 claim 32(iv)), a 4-1BB costimulatory domain (i.e., the limitations of instant claims 21 and 22; App ‘258 claim 32(iii)).
The invention encompassed by the instant claims is a prima facie obvious variant of the invention claimed by App ‘258 in view of Suarez et al. for the same reasons discussed for Pat ‘417 supra, especially in the absence of evidence to the contrary. This is a provisional double patenting rejection.
Claims 6 and 10 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 21-57 of copending Application No. 18/381,258 (App ‘258) in view of Suarez et al. (supra), as applied to claims 1, 2, 13-15, 17, 19-22 and 27 above, and further in view of Michie et al. (supra) and Bilim et al. (supra).
The combined teachings of App ‘258 in view of Suarez et al. has been discussed supra. The combined references do not teach the CAR expressing cell further expressing a peptide SMAC inhibitor that can be expressed by the CAR-T cell (i.e., the limitations of instant claim 6).
The invention encompassed by the instant claims is a prima facie obvious variant of the invention claimed by App ‘258 in view of Suarez et al., and further in view of Michie et al. and Bilim et al. for the same reasons discussed in the 35 U.S.C. § 103 rejection supra, especially in the absence of evidence to the contrary. This is a provisional double patenting rejection.
Claims 25, 26, and 46 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 21-57 of copending Application No. 18/381,258 (App ‘258) in view of Suarez et al. (supra), as applied to claims 1, 2, 13-15, 17, 19-22 and 27 above, and further in view of Johnson et al. (supra).
The combined teachings of App ‘258 in view of Suarez et al. has been discussed supra. The combined references do not teach the CAR expressing cell further expressing a RNA PRR activator such as 7SL (i.e., the limitations of instant claims 25, 26, and 46).
The invention encompassed by the instant claims is a prima facie obvious variant of the invention claimed by Pat ‘417 in view of Suarez et al., and further in view of Johnson et al. for the same reasons discussed in the 35 U.S.C. § 103 rejection supra, especially in the absence of evidence to the contrary. This is a provisional double patenting rejection.
Claims 1, 2, 13-15, 17, 20-22 and 27 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-66 of copending Application No. 18/682,232 (App ‘232) in view of Suarez et al. (supra).
App ‘232 claims nucleic acids encoding chimeric antigen receptor comprising an antigen binding domain, a TM domain, an ICD domain, and a costimulatory domain (claim 1), as well as cells expressing the nucleic acid (claims 22, 24).
App ‘232 additionally claims the cell can be a T-cell (i.e., the limitations of instant claim 14; App ‘232 claim 42), the antigen binding domain is an scFv (i.e., the limitations of instant claim 15; App ‘232 claim 37), the antigen is a tumor associated CD19 (i.e., the limitations of instant claims 13 and 17; App ‘232 claim 35), a CD3ζ ICD (i.e., the limitations of instant claim 20; App ‘232 claim 40), a 4-1BB costimulatory domain (i.e., the limitations of instant claims 21 and 22; App ‘232 claim 39).
The invention encompassed by the instant claims is a prima facie obvious variant of the invention claimed by App ‘232 in view of Suarez et al. for the same reasons discussed for Pat ‘417 supra, especially in the absence of evidence to the contrary. This is a provisional double patenting rejection.
Claims 6 and 10 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-66 of copending Application No. 18/682,232 (App ‘232) in view of Suarez et al. (supra), as applied to claims 1, 2, 13-15, 17, 20-22 and 27 above, and further in view of Michie et al. (supra) and Bilim et al. (supra).
The combined teachings of App ‘232 in view of Suarez et al. has been discussed supra. The combined references do not teach the CAR expressing cell further expressing a peptide SMAC inhibitor that can be expressed by the CAR-T cell (i.e., the limitations of instant claim 6).
The invention encompassed by the instant claims is a prima facie obvious variant of the invention claimed by App ‘232 in view of Suarez et al., and further in view of Michie et al. and Bilim et al. for the same reasons discussed in the 35 U.S.C. § 103 rejection supra, especially in the absence of evidence to the contrary. This is a provisional double patenting rejection.
Claims 25, 26, and 46 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-66 of copending Application No. 18/682,232 (App ‘232) in view of Suarez et al. (supra), as applied to claims 1, 2, 13-15, 17, 20-22 and 27 above, and further in view of Johnson et al. (supra).
The combined teachings of App ‘232 in view of Suarez et al. has been discussed supra. The combined references do not teach the CAR expressing cell further expressing a RNA PRR activator such as 7SL (i.e., the limitations of instant claims 25, 26, and 46).
The invention encompassed by the instant claims is a prima facie obvious variant of the invention claimed by App ‘232 in view of Suarez et al., and further in view of Johnson et al. for the same reasons discussed in the 35 U.S.C. § 103 rejection supra, especially in the absence of evidence to the contrary. This is a provisional double patenting rejection.
Claims 1, 2, 13-15, 19-21 and 27 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-31 of copending Application No. 18/684,598 (App ‘598) in view of Suarez et al. (supra).
App ‘598 claims chimeric antigen receptors comprising an antigen binding domain, a TM domain, an ICD domain, and a costimulatory domain (claim 1), as well as cells expressing the CAR (claim 22).
App ‘598 additionally claims the cell can be a T-cell (i.e., the limitations of instant claim 14; App ‘598 claim 23), the antigen binding domain is an scFv (i.e., the limitations of instant claim 15; App ‘598 claim 3), the antigen is a tumor associated BCR (i.e., the limitations of instant claim 13; App ‘598 claim 6), a CD8 TM domain (i.e., the limitations of instant claim 19; App ‘598 claim 19), a CD3ζ ICD (i.e., the limitations of instant claim 20; App ‘598 claim 10), a 4-1BB costimulatory domain (i.e., the limitations of instant claim 21; App ‘598 claim 13).
The invention encompassed by the instant claims is a prima facie obvious variant of the invention claimed by App ‘598 in view of Suarez et al. for the same reasons discussed for Pat ‘417 supra, especially in the absence of evidence to the contrary. This is a provisional double patenting rejection.
Claims 6 and 10 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-31 of copending Application No. 18/684,598 (App ‘598) in view of Suarez et al. (supra), as applied to claims 1, 2, 13-15, 19-21 and 27 above, and further in view of Michie et al. (supra) and Bilim et al. (supra).
The combined teachings of App ‘598 in view of Suarez et al. has been discussed supra. The combined references do not teach the CAR expressing cell further expressing a peptide SMAC inhibitor that can be expressed by the CAR-T cell (i.e., the limitations of instant claim 6).
The invention encompassed by the instant claims is a prima facie obvious variant of the invention claimed by App ‘598 in view of Suarez et al., and further in view of Michie et al. and Bilim et al. for the same reasons discussed in the 35 U.S.C. § 103 rejection supra, especially in the absence of evidence to the contrary. This is a provisional double patenting rejection.
Claims 25, 26, and 46 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-31 of copending Application No. 18/684,598 (App ‘598) in view of Suarez et al. (supra), as applied to claims 1, 2, 13-15, 19-21 and 27 above, and further in view of Johnson et al. (supra).
The combined teachings of App ‘598 in view of Suarez et al. has been discussed supra. The combined references do not teach the CAR expressing cell further expressing a RNA PRR activator such as 7SL (i.e., the limitations of instant claims 25, 26, and 46).
The invention encompassed by the instant claims is a prima facie obvious variant of the invention claimed by App ‘598 in view of Suarez et al., and further in view of Johnson et al. for the same reasons discussed in the 35 U.S.C. § 103 rejection supra, especially in the absence of evidence to the contrary. This is a provisional double patenting rejection.
Claims 1, 2, 13-15, 17, 19-22 and 27 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 7, 21, 37, 47, 51, 61, 64, 68, 71, 78, 79, 84, 86, 87, and 90 of copending Application No. 18/981,066 (App ‘066) in view of Ying et al. (Nat Med. 2019 Jun;25(6):947-953. doi: 10.1038/s41591-019-0421-7, supra).
App ‘066 claims nucleic acids comprising a CAR and a SHP inhibitor with a ITIM mutation (i.e., a non-natural therapeutic peptide), wherein the CAR comprises an antigen binding domain, a TM domain, and an ICD (claim 47). App ‘066 additionally claims modified cells expressing the CAR and SHP inhibitor (claim 68), and the CAR and SHP inhibitor are expressed from the same construct (i.e., the limitations of instant claims 1 and 2).
App ‘066 claims the CAR binds a tumor antigen (claim 51), meeting the limitations of instant claim 13.
App ‘066 does not claim the CAR-T cell expressing an anti-CD19 CAR (i.e., the limitations of instant claim 17).
Ying et al., in the same field of endeavor, teaches the anti-CD19 CAR CD19-BBz (Abstract, Fig. 1):
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Ying et al. further teaches the anti-CD19 CAR-T cells has potent efficacy with lower adverse effects (Table 2, Fig. 3, pg. 950): “…these data demonstrate that CD19-BBz(86) CAR T cell therapy has potent clinical efficacy without causing any neurological toxicity or severe CRS (greater than grade 1).” Ying et al. teaches that the CAR-T therapy comprising this CAR successfully treats lymphoma (Fig. 2).
Ying et al. teaches the anti-CD19 CAR comprises an anti-CD19 scFv, a CD8α TM domain, a 4-1BB costimulatory domain, and a CD3ζ signaling domain (Fig. 1, Methods): “…comprising FMC63 scFv, the extracellular domain and transmembrane regions (71 amino acids) of human CD8α, the cytoplasmic region of human 4-1BB, and the cytoplasmic part of the human CD3ζ molecule…”, which are the limitations of instant claims 17 and 19-22.
It would have been obvious to one with ordinary skill in the art to have modified the invention claimed by App ‘066 in view of Ying et al. to make a modified cell expressing the CD19-BBz and SHP inhibitor (i.e., the limitations of instant claims 14, 15, 17, and 19-22) with a reasonable expectation of success, as Ying et al teaches methods of generating such CAR-T cells. One would have been motivated to make this change to engineer the CAR-T cell of App ‘066 to target treat CD19 expressing cancers such as lymphoma.
The invention encompassed by the instant claims is a prima facie obvious variant of the invention claimed by App ‘066 in view of Ying et al., especially in the absence of evidence to the contrary. This is a provisional double patenting rejection. This is a provisional double patenting rejection.
Claims 6 and 10 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 7, 21, 37, 47, 51, 61, 64, 68, 71, 78, 79, 84, 86, 87, and 90 of copending Application No. 18/981,066 (App ‘066) in view of Ying et al. (supra), as applied to claims 1, 2, 13-15, 17, 19-22 and 27 above, and further in view of Michie et al. (supra) and Bilim et al. (supra).
The combined teachings of App ‘066 in view of Ying et al. has been discussed supra. The combined references do not teach the CAR expressing cell further expressing a peptide SMAC inhibitor that can be expressed by the CAR-T cell (i.e., the limitations of instant claim 6).
The invention encompassed by the instant claims is a prima facie obvious variant of the invention claimed by App ‘066 in view of Ying et al., and further in view of Michie et al. and Bilim et al. for the same reasons discussed in the 35 U.S.C. § 103 rejection supra, especially in the absence of evidence to the contrary. This is a provisional double patenting rejection. This is a provisional double patenting rejection.
Claims 25, 26, and 46 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-31 of copending Application No. 18/684,598 (App ‘598) in view of Suarez et al. (supra), as applied to claims 1, 2, 13-15, 17, 19-22 and 27 above, and further in view of Johnson et al. (supra).
The combined teachings of App ‘066 in view of Ying et al. has been discussed supra. The combined references do not teach the CAR expressing cell further expressing a RNA PRR activator such as 7SL (i.e., the limitations of instant claims 25, 26, and 46).
The invention encompassed by the instant claims is a prima facie obvious variant of the invention claimed by App ‘066 in view of Ying et al., and further in view of Johnson et al. for the same reasons discussed in the 35 U.S.C. § 103 rejection supra, especially in the absence of evidence to the contrary. This is a provisional double patenting rejection. This is a provisional double patenting rejection.
Conclusion
No claim is allowed.
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/ALEC JON PETERS/Examiner, Art Unit 1641
/MISOOK YU/Supervisory Patent Examiner, Art Unit 1641
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