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 11/17/2023, is acknowledged.
Claims 18-28, 31-33, 35-39, and 41-46 are cancelled.
Claims 1-17, 29, 30, 34, 40, and 47-50 are currently pending.
Election/Restrictions
Applicants’ election without traverse of Group I, claims 1-17, 29, and 30, directed to a conditional CAR or synNotch and the Species of: i) a CAR; ii) biotin; iii) NHS-ester conjugation; iv) trastuzumab; v) a light stimulus reactive group at 365nm; and vi) 4-1BB, filed on 3/16/2026, is acknowledged.
Claims 6, 13, 14, 29, and 30 are drawn to unelected species.
Claims 6, 13, 14, 29, 30, 34, 40, and 47-50 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to nonelected inventions and/or species.
Claims 1-5, 7-12, and 15-17 are under examination as reading on a universal CAR comprising a receptor that targets biotin, a conditional adapter molecule comprising NHS-ester conjugation, a trastuzumab antigen recognition element, a 365nm light reactive stimulus reactive group, and a 4-1BB co-stimulatory domain.
Regarding claim 3, the elected species of “NHS-ester conjugation” is under examination. The search and examination will extend to other species in the claim once the elected species has been found to be allowable.
Priority
Applicant’s claim for the benefit of a prior-filed U S. Provisional Application No. 63/110,194, filed on November 5, 2020, is acknowledged.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 5/05/2023, 1/07/2025, and 3/27/2026 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.
Specification
The use of the terms:
THIOMAB™ (¶[4], [11], [79], and claim 3);
Herceptin™ (¶[5], [16], [52], [53], [82], [86], [173], [193]);
SNAP-tag™ (¶[45], [55], [75], [79], [197], [198], [201]);
CLIP-tag™ (¶[79]);
HaloTag™ (¶[79]);
Lipofectin™ (¶[109]);
Lipofectamine™ (¶[109];
GIBCO™ (¶[109]);
SUPERFECT™ (¶[109]);
TRANSFECTAM™ (¶[109]); and
CellEvent™ (¶[192]);
which are trade names or marks used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Interpretation
Instant claim 3 recites:
“The universal CAR or conditional universal synNotch of claim 1, wherein the adaptor molecule comprises NHS- ester conjugation, disulfide re-stapling, glycan conjugating chemistry, a recombinant antibody with tag ligand incorporation through one or more short peptide tags, sortase mediated ligation, THIOMABs, chemical ligation, split inteins, and/or unnatural amino acids.”
The specification defines “adaptor molecule” (¶[79]):
“Both the universal synNotch receptors and the universal CARs disclosed herein comprise adaptor molecules. These adaptor molecules facilitate the formation of a covalent bond with an antigen recognition element (such as for example, an antibody or antibody fragment). The binding interaction can be a covalent bond, non-covalent bond, or other interaction such as a receptor-ligand or antibody-antigen/peptide/protein binding interaction (such as, for example FITC and anti-FITC or biotin/avidin). ·when covalently bonded, covalent bonding can occur through pi-clamp; ligand directed tosyl chemistry; recombinant antibodies with tag ligand incorporation (such as, for example, BG or BC incorporation) through short peptide tags, sortase mediated labeling~ unnatural amino acid mutagenesis followed by 'click' chemistry, [3+2] cycloaddition, split inteins, THIOMABs, tetrazine ligation, Staudinger ligation, imine formation, thiol-ene reaction, native chemical ligation; biotin ligase mediated labeling; lipoic acid ligase mediated labeling; NHS-ester conjugation, conjugation to cysteine, disulfide re-stapling via bis-sulfones or other reagents, glycan conjugating chemistry, or formyl glycine conversion.”
The specification discloses that adaptor molecules do not comprise the conjugation chemistry that covalently links the antigen recognition element. The adaptor molecules are covalently attached to the antigen recognition element using one of the methods recited in instant claim 3. For example, instant Figure 3 discloses that NHS-ester conjugation is used to conjugate an O6-benzylgruanine to an antibody, and then a T-cell comprising a CAR with the SNAP-tag receptor reacts with the O6-benzylgruanine to form a covalent bond between the SNAP-tag receptor and the adaptor molecule:
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For the purposes of examination, claim 3 is interpreted as the universal CAR of claim 1, wherein the adaptor molecule is conjugated to a tag via the elected species of NHS-ester conjugation recited in the claim.
Claim Objections
Claim 7 is objected to because the claim recites “…stimulus reactive group is reactive comprises a light, enzyme activity…” and should most likely recite “…stimulus reactive group is reactive to light, enzyme activity…” to correct a minor grammatical issue.
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 1-5, 7-12, and 15-17 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claims 1-5, 7-12, and 15-17 encompasses CARs comprising a broad genus of receptors with no recited structure and the function of “targets a tag ligand of a conditional adaptor molecule” (claims 1, 3-5, 7-12, and 15-17) or “targets biotin” (the elected Species in claim 2), which encompasses a genus of millions to billions of different receptors with the recited function.
Claims 1-5, 7-12, and 15-17 additionally encompass CARs comprising a broad genus of groups with no recited structure and the function of “stimulus reactive group” (claims 1-5 and 15-17), “light-reactive group” (claim 7), “photocleavable linker” (claims 8 and 9), “light-reactive caging group” (claims 10 and 11), or “reactive to 365nm light” (claim 12).
Claims 1, 3-5, 7-12, and 15-17 further comprises CARs comprising a broad genus of ligands with no recited structure and the function of “tag ligand”.
However, the specification fails to provide adequate written description support for the essential structural features that provide the recited functions of “targets a tag ligand”, “stimulus reactive group”, and “tag ligand”. The Guidelines for the Examination of Patent Applications Under the 35 U.S.C. 112(a) or U.S.C 112, ¶ 1 "Written Description" Requirement make clear that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the genus.
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).
Regarding the claimed genera of receptors with the function of “targets a tag ligand” (claims 1, 3-5, 7-12, and 15-17) or “targets biotin” (claim 2);
The specification discloses universal CARs that comprise an adaptor molecule that will react with a modified antibody, leading to covalent conjugation of the antibody to the CAR and functionalization of the CAR (Example 1). The adaptor molecule can be any technology that supports the covalent conjugation of an antigen recognition element to the CAR. The specification discloses different reactions that can create the covalent bond (¶[79]), as well as specific adaptor molecules with this function such as biotin/avidin, SNAP-tag™, Halo-tag™, CLIP-tag™, SpyTag, SnoopTag, and Isopep-tag (¶[79]). All of the disclosed tags are polypeptides/proteins that covalently bond to a specific partner via a specific chemical reaction or intermolecular interactions.
The specification also provides working examples disclosing the engineering and function of the universal CAR where the adaptor molecule is a SNAP-tag (Example 1). The SNAP-tag works via reacting with a benzylguanine (i.e., “BG”; Figure 3). A viral vector encoding the SNAP-CAR was transduced into T-cells to create SNAP-CAR T cells, which can be co-administered with the antibodies Rituximab, FMC63, Cetuximab, and Herceptin that have been conjugated to BG. Cell lines expressing the appropriate antigens were co-incubated with the antibody and the SNAP-CAR T cells to form an active CAR that leads to T-cell activation (Example 1).
The specification further discloses cells comprising CARs that bind to biotin (Example 1(d)-(e)). All of these used a specific streptavidin polypeptide structure to bind to biotin.
Regarding the claimed genera of groups with no recited structure and the function of “stimulus reactive group” (claims 1-5 and 15-17), “light-reactive group” (claim 7), “photocleavable linker” (claims 8 and 9), “light-reactive caging group” (claims 10 and 11), or “reactive to 365nm light” (claim 12);
The specification discloses that a “stimulus reactive group” is also known as a caging group, blocks tag ligand interactions with its cognate receptor or adapter molecule (¶[76]). The specification discloses that caging groups can possibly be developed to react to stimuli such as light at different wavelengths, enzymes, small molecules, pH, hypoxia, hydrogen peroxide, and ROS (¶[6]).
Specific photocleavable linkers are disclosed. Fig. 5A discloses a 365nm photocleavable group:
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Fig. 7A discloses another 365nm photocleavable group:
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Fig. 13 discloses a 365nm photocleavable group (arrow), as well as photocleavable groups that react to 405nm, 544nm, and 690nm light:
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Fig, 17 discloses photocleavable groups that react to 544 and 780nm light:
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Fig. 6A (below) and 8A disclose a phosphene (small molecule) cleavable group:
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Fig 18 discloses a phosphene-cleavable and a tetrazine-cleavable group:
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Fig. 19 discloses a ROS-cleavable group, a peroxide cleavable group, and short peptides that are cleavable by legumain and MMP 2/9/14:
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The specification discloses three specific examples of a structure that has the function of a 365nm light cleavable group, one example each of structures that are cleaved by 405nm, 544nm, 690nm, or 780nm light, two examples of a phosphene cleavable group, one example of a tetrazine cleavable group, one example each of a ROS and a peroxide cleavable group, one example of a MMP 4/9/15 cleavable group, and one example of a legumain cleavable group.
Regarding the claimed genus of ligand with the function of “tag ligand” (claims 1, 3-5, 7-12, and 15-17);
The specification discloses specific tag ligands that react/bind to specific receptors that are not interchangeable with each other. The specification discloses that the SNAP-tag™ reacts with O6-benzylguanine to form a covalent bond, CLIP-tag™ reacts with O6-benzylcytosine to form a covalent bond, HaloTag™ reacts to chloroalkane to form a covalent bond, and SpyTag specifically reacts with the SpyCatcher peptide, and biotin is specifically bound by avidin/streptavidin (¶[79]).
The specification discloses two working examples of tags incorporated into universal CARs, which are SNAP-tag™ reacting to a O6-benzylguanine tag (Fig. 3), and a CAR with a streptavidin receptor that specifically interacts with a biotin tag (Example 1(d) and 1(e)).
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 specification discloses two working examples of “receptors” structures (SNAP-tag™ and streptavidin mSA2), that each react with two disclosed examples specific “tag” structures (O6-benzylguanine and biotin, respectively). The specification also discloses 12 different examples of structures that have the function of “stimulus reactive group”. However, the small number of disclosed structures of receptors, tags, and stimulus reactive groups do not sufficiently represent the structurally and functionally diverse genera of receptors, tags, and stimulus reactive groups encompassed by the claims to allow one with ordinary skill in the art to recognize common attributes or features possessed by the broadly claimed genera.
Given the broadly claimed genera of receptor molecules, tags, or stimulus reactive groups, and in the absence of sufficient disclosure of relevant identifying characteristics for the broadly claimed class of antigen binding molecules that bind to a ligand, 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.
The facts of AbbVie parallel the claimed invention and provide significant guidance on the inherent unpredictability of protein engineering and the effect of amino acid substitutions on protein function. Abbvie is similar to the Federal Circuit's discussion in Novozymes A/S et al. v. Dupont Nutrition Biosciences APS et al., 2013 WL 3779376, Case No. 2012-1433, C.A.Fed; in both, the Federal Circuit emphasized the unpredictability in the art associated with changes in a parent enzyme or protein that can be affected at one or more positions in the sequence by amino acid addition, deletion, or substitution with at least nineteen other possibilities, e.g., counting natural amino acid residues. The basis of the unpredictability is rooted in the same principles that make improvements rare, namely that numerous subtle differences between amino acid residues determine protein binding and function. Because the subtle energetic contributions of each of these interactions is extraordinarily difficult to precisely quantify, and because the number of these interactions is so high even for a single protein-protein interface, innumerable small inaccuracies are amplified into unpredictability. This unpredictability is axiomatic in the field of protein engineering.
For example, functionally defined genus claims can be inherently vulnerable to invalidity challenge for lack of written description support, especially in technology fields that are highly unpredictable, where it is difficult to establish a correlation between structure and function for the whole genus or to predict what would be covered by the functionally claimed genus. Ariad, 598 F.3d at 1351 ("[T]he level of detail required to satisfy the written description requirement varies depending on the nature and scope of the claims and on the complexity and predictability of the relevant technology."); see also Centocor Ortho Biotech, Inc. v. Abbott Labs., 636 F.3d 1341, 1352 (Fed. Cir. 2011) (noting the technical challenges in developing fully human antibodies of a known human protein). It is true that functionally defined claims can meet the written description requirement if a reasonable structure-function correlation is established, whether by the inventor as described in the specification or known in the art at the time of the filing date. Enzo Biochem, Inc. v. Gen-Probe Inc., 323 F.3d 956, 964 (Fed. Cir. 2002). However, the record here does not indicate such an established correlation. Instead, AbbVie used a trial and error approach to modify individual amino acids in order to improve the IL-12 binding affinity. Moreover, the '128 and '485 patents of AbbVie do not describe any common structural features of the claimed antibodies. The asserted claims attempt to claim every fully human IL-12antibody that would achieve a desired result, i.e., high binding affinity and neutralizing activity, and cover an antibody as different as Stelara, whereas the patents do not describe representative examples to support the full scope of the claims.
Regarding the claimed genera of receptors with the function of “targets a tag ligand” (claims 1, 3-5, 7-12, and 15-17) or “targets biotin” (claim 2);
The specification discloses two working examples of receptors that have the function of “targets a tag ligand” or “targets biotin”, the SNAP-tag™ enzyme that specifically reacts with O6-benzylguanine to form a covalent bond, and streptavidin mSA2 that specifically binds to biotin. Neither the specification nor the prior art provides sufficient structure-identifying characteristics in the broadly claimed genera of receptors with little to no structure and the function of “targets a tag ligand” or “targets biotin”. The instant specification provides no guidance on how to generate receptor molecules with the function of “targets a tag ligand” or “targets biotin”, or how to distinguish those receptor compounds with the recited functions from those without. Undue experimentation would be required by one of ordinary skill in the art to produce the broad genus of compounds with the recited functions encompassed by the claims.
Regarding the claimed genera of groups with no recited structure and the function of “stimulus reactive group” (claims 1-5 and 15-17), “light-reactive group” (claim 7), “photocleavable linker” (claims 8 and 9), “light-reactive caging group” (claims 10 and 11), or “reactive to 365nm light” (claim 12);
The specification discloses three specific examples of a structure that has the function of a 365nm light cleavable group, one example each of structures that are cleaved by 405nm, 544nm, 690nm, or 780nm light, two examples of a phosphene cleavable group, one example of a tetrazine cleavable group, one example each of a ROS and a peroxide cleavable group, one example of a MMP 4/9/15 cleavable group, and one example of a legumain cleavable group. Neither the specification nor the prior art provides sufficient structural-identifying characteristics or structure-function relationship to allow one with ordinary skill in the art to identify other compounds with the recited stimulus-reactive functions recited in the claims. For example, the instant specification provides no guidance on how to generate receptor molecules with the function of “light-reactive group”, or how to distinguish those receptor compounds with the recited functions from those without.
Regarding the claimed genus of ligand with the function of “tag ligand” (claims 1, 3-5, 7-12, and 15-17);
The specification discloses only two working examples of structures with the function of “tag ligand” that were incorporated into universal CARs – O6-benzylguanine, which only reacts with SNAP-tag™, and biotin, which is specifically bound to avidin/streptavidin. Neither the specification nor the prior art provides sufficient structural-identifying characteristics or structure-function relationship to allow one with ordinary skill in the art to identify other compounds with the recited function of “tag ligand” in the claims. Neither the instant specification nor the prior art provides guidance on how to generate other compounds with the function of “tag ligand”, or how to distinguish those receptor compounds with the recited functions from those without.
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 anti-TMPRSS6 antibodies or antigen binding fragments thereof 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 1-5, 7-12, and 15-17 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.
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 3 and 5 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 3 recites the limitation "…wherein the conditional adaptor molecule…" in line 2. There is insufficient antecedent basis for this limitation in the claim. Claim 3 depends on claim 1, and claim 1 recites “a conditional adaptor molecule” on three separate occasions (lines 3, 4, and 6). The conditional adaptor molecules are interpreted to be different from each other due to the recitation of “a conditional adaptor molecule” in each occurrence. Instant claim 3 recites “…wherein the conditional adaptor…” It is currently unclear which of the three recited “conditional adaptor molecules” claim 3 is referring to.
Claim 5 contains the trademark/trade name Herceptin®. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe trastuzumab and, accordingly, the identification/description is indefinite. It is recommended to amend the claim to only recite trastuzumab and not Herceptin™ to resolve this issue.
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, 7, and 15-17 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Tamada et al. (Clin Cancer Res. 2012 Dec 1;18(23):6436-45. doi: 10.1158/1078-0432.CCR-12-1449).
Claim 1 is claiming a conditional CAR comprising a receptor that targets a tag ligand, a hinge domain, a signaling domain, and a conditional adapter comprising an antigen recognition element, a stimulus reactive group, and a tag ligand.
Tamada et al. teaches a universal CAR system (Fig. 1A):
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The universal CAR system comprises a CAR comprising an anti-FITC scFv (“a receptor that targets a tag ligand on a conditional adaptor molecule”), a CD8 hinge and TM domain (pg. 6437: “…scFv against FITC was generated according to the previous report and linked to the hinge and transmembrane regions of the human CD8a chain…”), a 4-1BB costimulatory domain, and a CD3ζ intracellular signaling domain. The system additionally comprises an antibody (“an antigen recognition element”) conjugated to FITC. In this case, FITC serves as a “tag” that is bound by the anti-FITC scFv of the CAR (see Fig. 1A supra), as well as a “stimulus reactive group”, as it is a fluorescent dye that emits light in response to excitation with a certain light wavelength (Introduction): “FITC is a fluochrome dye that can be cheaply and easily conjugated with Ab and safely used in human body…”
Thus, Tamada et al. teaches the limitations of instant claim 1.
Regarding claim 7, FITC is stimulated upon exposure to certain wavelengths of light, meeting the claim limitations.
Regarding claims 15-17, Tamada et al. teaches the CAR is expressed on the surface of a T-cell and comprises the 4-1BB costimulatory domain (see Fig. 1 supra), meeting the claim limitations.
The reference teachings anticipate the 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 1-4, 7-12, and 15-17 are rejected under 35 U.S.C. 103 as being unpatentable over Lohmueller et al. (Oncoimmunology. 2017 Oct 26;7(1):e1368604. doi: 10.1080/2162402X.2017.1368604) in view of Terai et al. (Chem Biol. 2011 Oct 28;18(10):1261-72. doi: 10.1016/j.chembiol.2011.09.007).
Claim 1 is claiming a conditional CAR comprising a receptor that targets a tag ligand, a hinge domain, a signaling domain, and a conditional adapter comprising an antigen recognition element, a stimulus reactive group, and a tag ligand.
Lohmueller et al. teaches CARs engineered for universal tumor targeting (Abstract). The CAR is expressed on T-cells (Introduction): “…mSA2 CAR T cells are efficiently stimulated by plate-immobilized biotin…”. Lohmueller et al. further teaches the CAR comprises a mSA2 streptavidin receptor that specifically binds to the biotin tag, a CD8α hinge domain, a CD28 TM domain, a 4-1BB costimulatory domain, and a CD3ζ intracellular signaling domain (Fig. 1):
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Lohmueller et al. further teaches the CAR system further comprising an anti-CD20 antibody rituximab that has been biotinylated (pg. e1368604-2): “…mSA2 CAR T cells responded by up-regulating T cell activation markers in a dose-responsive manner to the biotinylated Rituximab (Fig. 3A). They also produced IFNg (Fig. 3B) and performed target cell lysis…”
Thus, Lohmueller et al. teaches a CAR system comprising a CAR comprising a mSA2 receptor that recognizes the biotin tag, a hinge domain, a 4-1BB costimulatory signaling domain, and a CD3ζ intracellular signaling domain, as well as a conditional adaptor molecule comprising an anti-CD20 antibody rituximab conjugated to the biotin tag.
Lohmueller et al. does not teach the conditional adaptor molecule further comprising a stimulus reactive group (i.e., the limitations of instant claim 1).
Terai et al., in the same field of endeavor, teaches caged biotin derivatives that are activated upon exposure to UV light (Abstract): “…we designed and synthesized
photoreleasable biotins, which show greatly reduced affinity for (strept)avidin, but recover native affinity after UV irradiation. For application at the cell surface, we introduced an amine-reactive moiety into these ‘‘caged’’ biotin molecules.” Also see Fig. 1:
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Terai et al. teaches photoactivatable caged biotin with a nitrobenzyl-based photocleavable group that reacts with 365nm light (pg. 1264): “[w]e next designed and synthesized two photoactivatable biotin derivatives…[t]hese compounds consist of biotin and a nitrobenzyl-based photo-removable protecting group that can be excited at 365 nm with a high uncaging rate and a high photolysis quantum yield.” Also see Fig. 2:
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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 Lohmueller et al. in view of Terai et al. to use a photoactivatable caged biotin in the CAR system of Lohmueller et al. (i.e., the limitations of instant claim 1) with a reasonable expectation of success, as Terai et al. teaches such a caged biotin that can be used in place of the biotin tag taught by Lohmueller et al. One would have been motivated to make this change for the purposes of generating a photoactivatable universal CAR system to provide greater spaciotemporal control of the CAR mSA2 binding to the biotin-tagged antibody by making the system activatable with 365nm light.
Regarding claim 2, Lohmueller et al. teaches the biotin tag (supra), meeting the claim limitations.
Regarding claim 3, Lohmueller et al. teaches that the biotin is conjugated to the antibody via NHS ester conjugation (“Antibody biotinylation” section), meeting the claim limitations.
Regarding claim 4, Lohmueller teaches the antigen recognition element comprising the rituximab antibody, meeting the claim limitations.
Regarding claim 7-12, the biotin caging group taught by Terai et al. is a light-reactive photocleavable nitrobenzyl caging group that is stimulated by 365nm light, and blocks biotin/avidin interactions until light exposure (supra), meeting the claim limitations.
Regarding claims 15-17, Lohmueller teaches the CAR comprising the 4-1BB costimulatory domain, and the CAR is expressed on T-cells (supra), meeting the claim limitations.
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.
Claim 5 is rejected under 35 U.S.C. 103 as being unpatentable over Lohmueller et al. (supra) in view of Terai et al. (supra) as applied to claims 1-4, 7-12, and 15-17 above, and further in view of Sapino et al. (Ann Oncol. 2007 Dec;18(12):1963-8. doi: 10.1093/annonc/mdm417).
The combined teachings of Lohmueller et al. in view of Terai et al. have been discussed supra. The combined teachings do not teach the CAR system comprising a biotinylated trastuzumab.
Sapino et al., in the same field of endeavor, teaches biotinylated Herceptin™ that can be used to target Her2 expressing tumors in patients (Abstract): “[b]iotin-labeled trastuzumab (BioHER) can be used…[t]he effect of BiotHER positivity on response rate (RR), time to progression and survival were studied by univariate and multivariate analysis in patients presenting HER2-amplified breast cancer.” The BioHER remained functional and the conjugated biotin binds to streptavidin (pg. 1964): “[w]e have therefore conjugated the NH2 groups of trastuzumab with biotin and directly added the biotinylated antibody to tissue sections. Biotin labeling was revealed with horseradish peroxidase (HRP)-conjugated streptavidin”.
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 combined references of Lohmueller et al. and Terai et al. further in view of Sapino et al. to use the universal CAR system with a biotinylated Herceptin™ antibody with a reasonable expectation of success, as one with ordinary skill in the art would recognize that any biotinylated antibody would be recognized by the mSA2 CAR taught by Lohmueller et al. and Terai et al., including the biotinylated Herceptin™ of Sapino et al. One would have been motivated to make this change for the purposes of targeting and treating Her2 expressing cancers.
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, 4, 7-12, and 15-17 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 11,117,936 (Pat ‘936) in view of Terai et al. (Chem Biol. 2011 Oct 28;18(10):1261-72. doi: 10.1016/j.chembiol.2011.09.007, supra). Although the claims at issue are not identical, they are not patentably distinct from each other.
Pat ‘936 claims methods comprising administration of a CAR system comprising a biotinylated antibody (i.e., “a conditional adaptor molecule comprising an antigen recognition element” and “a tag ligand”) and CD3 T-cells expressing a CAR comprising residues 1-369 of SEQ ID NO: 12. SEQ ID NO: 12 is the amino acid sequence of a CAR comprising the mSA2 biotin-binding domain, a CD8 hinge domain, a CD28 TM domain, a 4-1BB costimulatory domain, and a CD3ζ intracellular signaling domain.
Pat ’936 does not claim the CAR system comprising a biotinylated antibody with a stimulus reactive group (i.e., the limitations of instant claim 1).
Terai et al., in the same field of endeavor, teaches caged biotin derivatives that are activated upon exposure to UV light (Abstract): “…we designed and synthesized
photoreleasable biotins, which show greatly reduced affinity for (strept)avidin, but recover native affinity after UV irradiation. For application at the cell surface, we introduced an amine-reactive moiety into these ‘‘caged’’ biotin molecules.” Also see Fig. 1:
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Terai et al. teaches photoactivatable caged biotin with a nitrobenzyl-based photocleavable group that reacts with 365nm light (pg. 1264): “[w]e next designed and synthesized two photoactivatable biotin derivatives…[t]hese compounds consist of biotin and a nitrobenzyl-based photo-removable protecting group that can be excited at 365 nm with a high uncaging rate and a high photolysis quantum yield.” Also see Fig. 2:
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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 claimed by Pat ‘936 in view of Terai et al. to use a photoactivatable caged biotin in the CAR system claimed by Pat ‘936 (i.e., the limitations of instant claim 1) with a reasonable expectation of success, as Terai et al. teaches such a caged biotin that can be used in place of the biotin tag claimed by Pat ‘936. One would have been motivated to make this change for the purposes of generating a photoactivatable universal CAR system to provide greater spaciotemporal control of the CAR mSA2 binding to the biotin-tagged antibody by making the system activatable with 365nm light.
Regarding claim 2, Pat ‘936 claims the biotin tag (claim 1), meeting the claim limitations.
Regarding claim 4, Pat ‘936 claims the antigen recognition element comprising an antibody (claim 1), meeting the claim limitations.
Regarding claim 7-12, the biotin caging group taught by Terai et al. is a light-reactive photocleavable nitrobenzyl caging group that is stimulated by 365nm light, and blocks biotin/avidin interactions until light exposure (supra), meeting the claim limitations.
Regarding claims 15-17, Pat ‘936 claims the CAR comprising the 4-1BB costimulatory domain, and the CAR is expressed on T-cells (claim 1), meeting the claim limitations.
Therefore, the invention encompassed by the instant application is a prima facie obvious variant of the invention claimed by Pat ‘936 in view of Terai et al., especially in absence to evidence to the contrary.
Claims 3 and 5 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 11,117,936 (Pat ‘936, supra) in view of Terai et al. (supra), as applied to claims 1, 2, 4, 7-12, and 15-17 above, and further in view of Sapino et al. (Ann Oncol. 2007 Dec;18(12):1963-8. doi: 10.1093/annonc/mdm417, supra).
The combined teachings of Pat ‘936 in view of Terai et al. are discussed supra. The combined references do not teach the adapter molecule comprising Herceptin™ and NHS-ester conjugation (i.e., the limitations of instant claim 3 and 5).
Sapino et al., in the same field of endeavor, teaches biotinylated Herceptin™ that can be used to target Her2 expressing tumors in patients (Abstract): “[b]iotin-labeled trastuzumab (BioHER) can be used…[t]he effect of BiotHER positivity on response rate (RR), time to progression and survival were studied by univariate and multivariate analysis in patients presenting HER2-amplified breast cancer.” The BioHER remained functional and the conjugated biotin binds to streptavidin (pg. 1964): “[w]e have therefore conjugated the NH2 groups of trastuzumab with biotin and directly added the biotinylated antibody to tissue sections. Biotin labeling was revealed with horseradish peroxidase (HRP)-conjugated streptavidin”. Sapino et al. further teaches that NHS-ester conjugation is used to conjugate the biotin to the Herceptin™ (“patients and methods” section): “…1 mg of trastuzumab, commercially available as Herceptin® (Roche, Hertfordshire, UK), was diluted in saline solution (1 mg/ml concentration) and dialyzed overnight in 0.1 M Na2CO3 (pH 8.5). To 1 ml of solution, 0.12 ml of e-caproylamido-biotin-n-hydroxy-succinimide ester (Biospa, Milano, Italia) was added. The preparation was mixed by gentle agitation for 4 h at room temperature and dialyzed in phosphate-buffered saline (PBS). The product, designated BiotHER stock solution…”
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 claimed by Pat ‘936 in view of Terai et al. further in view of Sapino et al. to use the universal CAR system with a biotinylated Herceptin™ antibody with a reasonable expectation of success, as one with ordinary skill in the art would recognize that any biotinylated antibody would be recognized by the mSA2 CAR taught by Pat ‘936 in view of Terai et al., including the biotinylated Herceptin™ of Sapino et al. One would have been motivated to make this change for the purposes of targeting and treating Her2 expressing cancers.
Regarding claim 3, Sapino et al. teaches the biotinylated Herceptin™ uses NHS-ester conjugation (see supra), meeting the claim limitations.
Therefore, the invention encompassed by the instant application is a prima facie obvious variant of the invention claimed by Pat ‘936 in view of Terai et al., and further in view of Sapino et al., especially in absence to evidence to the contrary.
Claims 1, 2, 4, 7-12, and 15-17 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of copending Application No. 18/816,891 (App ‘891) in view of Terai et al. (supra). Although the claims at issue are not identical, they are not patentably distinct from each other.
App ‘891 claims T-cells expressing CARs comprising SEQ ID NO: 11 or 12 (claims 1 and 11-13). SEQ ID NO: 11 is a CAR comprising a mSA2 receptor that targets the biotin tag ligand, a hinge domain, an intracellular signaling domain, and a 4-1BB costimulatory domain. App ‘891 additionally claims methods comprising administration of a CAR system comprising the CAR expressed on a T-cell and a biotinylated antibody (i.e., “antigen recognition element” and “tag”).
App ‘891 not claim the CAR system comprising a biotinylated antibody with a stimulus reactive group (i.e., the limitations of instant claim 1).
The invention encompassed by the instant claims is a prima facie obvious variant of the invention claimed by App ‘891 in view of Terai et al. for the same reasons discussed for Pat ‘936 supra. This is a provisional double patenting rejection.
Claims 3 and 5 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of copending Application No. 18/816,891 (App ‘891, supra) in view of Terai et al. (supra), as applied to claims 1, 2, 4, 7-12, and 15-17 above, and further in view of Sapino et al. (supra).
The invention encompassed by the instant claims is a prima facie obvious variant of the invention claimed by App ‘891 in view of Terai et al., and further in view of Sapino et al. for the same reasons discussed for Pat ‘936 supra. This is a provisional double patenting rejection.
Claims 1, 7-9, 12, and 15-17 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 6, 8-17, 19-23, 25-27, and 29-31 of copending Application No. 17/282,113 (App ‘113, allowed but patent not published) in view of Ankenbruck et al. (Angew Chem Int Ed Engl. 2018 Mar 5;57(11):2768-2798. doi: 10.1002/anie.201700171). Although the claims at issue are not identical, they are not patentably distinct from each other.
App ‘113 claims universal CAR systems comprising a CAR comprising an adaptor molecule that binds to O6-benzylguanine, a hinge domain, and a intracellular signaling domain, and an antibody comprising a O6-benzylguanine (claim 1).
App ‘113 does not claim the BG-conjugated antibody further comprising a stimulus reactive group such as a photocleavable linker.
Ankenbruck et al., in the same field of endeavor, teaches photocleavable groups that can be incorporated into SNAP-tag ligand conjugates to allow for 365nm light-mediated cleavage of the SNAP substrate from what it is conjugated to (Section 2.4 and Fig. 5).
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 claimed by App ‘113 in view of Ankenbruck et al. to incorporate the photocleavable group taught by Ankenbruck et al. into the SNAP-CAR system claimed by App ‘113 with a reasonable expectation of success, as Ankenbruck et al. teaches that this group can be successfully incorporated into SNAP ligand conjugates. One would have been motivated to make this change for the purposes of generating an optically controllable CAR system to allow for greater spaciotemporal control of the CAR activity.
Regarding claims 7-9 and 12, Ankenbruck et al. teaches that the photocleavable group is a nitrobenzyl group that reacts to 365nm light (Section 2.4 and Fig. 5), meeting the claim limitations.
Regarding claims 15-17, App ‘113 claims the CAR comprising a 4-1BB costimulatory domain (claim 9), as well as CAR-T cells comprising the CAR (claim 26), meeting the claim limitations.
The invention encompassed by the instant claims is a prima facie obvious variant of the invention claimed by App ‘113 in view of Ankenbruck et al., especially in absence of evidence to the contrary.
Claims 3-5 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 6, 8-17, 19-23, 25-27, and 29-31 of copending Application No. 17/282,113 (App ‘113, supra) in view of Ankenbruck et al. (supra), as applied to 1, 7-9, 12, and 15-17 above, and further in view of Lohmueller et al. 2020 (bioRxiv 2020.01.17.909895; doi: 10.1101/2020.01.17.909895).
The teachings of App ‘113 in view of Ankenbruck et al. have been discussed supra. App ‘113 further claims the antigen recognition element comprising the trastuzumab antibody (i.e., the limitations of instant claims 4 and 5).
The combined teachings do not teach the BG conjugated to the antibody via NHS ester conjugation (i.e., the limitations of instant claim 3).
Lohmueller et al. 2020, in the same field of endeavor, teaches that BG can be conjugated to antibodies for use with SNAP-CARs via NHS-ester conjugation (Fig. 1A):
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It would have been obvious to one with ordinary skill in the art to have modified the combined teachings of App ‘113 and Ankenbruck et al. further in view of Lohmueller et al. 2020 to have used NHS-ester chemistry to conjugate the BG moiety to the antibody, as Lohmueller et al. 2020 teaches this method. One would have been motivated to make this change to use an efficient way to conjugate BG to an antibody in the SNAP-CAR system of App ‘113 in view of Ankenbruck et al.
The invention encompassed by the instant claims is a prima facie obvious variant of the invention claimed by App ‘113 in view of Ankenbruck et al., and further in view of Lohmueller et al. 2020, especially in absence of evidence to the contrary.
Claims 1, 2, and 7-12 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 7-9, 20, 21, 24, 25, 30, 31, 38, 46-50, 54, and 55 of copending Application No. 19/525,424 (App ‘424) in view of Terai et al. (supra). Although the claims at issue are not identical, they are not patentably distinct from each other.
App ‘424 claims conditional adaptor molecules comprising T-L-A, where T is a tag ligand, L is a linker, and A is a moiety capable of binding a cell surface protein (i.e., “antigen recognition element”) comprising folate receptor, carbonic anhydrase, PSA, and PD-L1 (claim 1).
App ‘424 additionally claims a CAR system comprising the adapter molecule and a CAR comprising a receptor that is capable of binding to the tag, a hinge domain, and a signaling domain (claim 25), as well as cells comprising the CAR (claim 26).
App ‘424 not claim the CAR system comprising a biotinylated antibody with a stimulus reactive group (i.e., the limitations of instant claim 1).
The invention encompassed by the instant claims is a prima facie obvious variant of the invention claimed by App ‘424 in view of Terai et al. for the same reasons discussed for Pat ‘936 supra. This is a provisional double patenting rejection.
Claims 15-17 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 7-9, 20, 21, 24, 25, 30, 31, 38, 46-50, 54, and 55 of copending Application No. 19/525,424 (App ‘424, supra) in view of Terai et al. (supra), as applied to 1, 2, and 7-12 above, and further in view of Lohmueller et al. (Oncoimmunology. 2017 Oct 26;7(1):e1368604. doi: 10.1080/2162402X.2017.1368604, supra).
The teachings of App ‘424 in view of Terai et al. have been discussed supra. The combined teachings do not teach the CAR on a T-cell (the limitations of instant claim 17), or the CAR comprising a 4-1BB costimulatory domain (the limitations of instant claims 15 and 16).
Lohmueller et al., in the same field of endeavor, teaches mSA2 anti-biotin CARs that can be used in CAR systems (Fig. 1, see 35 U.S.C. § 103 rejection supra). Lohmueller et al. teaches these CARs on T-cells recognizes biotinylated adapter molecules such as antibodies (pg. e1368604-2): “…mSA2 CAR T cells responded by up-regulating T cell activation markers in a dose-responsive manner to the biotinylated Rituximab (Fig. 3A). They also produced IFNg (Fig. 3B) and performed target cell lysis…”
It would have been obvious to one with ordinary skill in the art to have modified the combined teachings of App ‘424 and Terai et al. further in view of Lohmueller et al. to use a CAR-T cell comprising a mSA2 CAR with a 4-1BB costimulatory domain (i.e., the limitations of instant claims 15-17) with a reasonable expectation of success, as App ‘424 in view of Terai et al. teaches CAR systems that recognize biotin, and Lohmueller et al. teaches such a CAR system with the mSA2 CAR with a 4-1BB costimulatory domain. One would have been motivated to make this change to use a functional biotin binding CAR in the CAR system of App ‘424 in view of Terai et al.
The invention encompassed by the instant claims is a prima facie obvious variant of the invention claimed by App ‘424 in view of Terai et al., and further in view of Lohmueller et al. 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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