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 .
Election/Restriction
REQUIREMENT FOR UNITY OF INVENTION
As provided in 37 CFR 1.475(a), a national stage application shall relate to one invention only or to a group of inventions so linked as to form a single general inventive concept (“requirement of unity of invention”). Where a group of inventions is claimed in a national stage application, the requirement of unity of invention shall be fulfilled only when there is a technical relationship among those inventions involving one or more of the same or corresponding special technical features. The expression “special technical features” shall mean those technical features that define a contribution which each of the claimed inventions, considered as a whole, makes over the prior art.
The determination whether a group of inventions is so linked as to form a single general inventive concept shall be made without regard to whether the inventions are claimed in separate claims or as alternatives within a single claim. See 37 CFR 1.475(e).
When Claims Are Directed to Multiple Categories of Inventions:
As provided in 37 CFR 1.475 (b), a national stage application containing claims to different categories of invention will be considered to have unity of invention if the claims are drawn only to one of the following combinations of categories:
(1) A product and a process specially adapted for the manufacture of said product; or
(2) A product and a process of use of said product; or
(3) A product, a process specially adapted for the manufacture of the said product, and a use of the said product; or
(4) A process and an apparatus or means specifically designed for carrying out the said process; or
(5) A product, a process specially adapted for the manufacture of the said product, and an apparatus or means specifically designed for carrying out the said process.
Otherwise, unity of invention might not be present. See 37 CFR 1.475 (c).
Restriction is required under 35 U.S.C. 121 and 372.
This application contains the following inventions or groups of inventions which are not so linked as to form a single general inventive concept under PCT Rule 13.1.
In accordance with 37 CFR 1.499, applicant is required, in reply to this action, to elect a single invention to which the claims must be restricted.
Group I, claims 30-31, 33-34, 37, 40, 42, 44, 50, 55-56, 59-60, 62, 65, 67, 69-70, and 76, drawn to a CAR bridging protein comprising a CAR-binding domain and an antigen-binding domain.
Group II, claim 78, drawn to a method of treating comprising administering to a subject the CAR bridging protein.
The groups of inventions listed above do not relate to a single general inventive concept under PCT Rule 13.1 because, under PCT Rule 13.2, they lack the same or corresponding special technical features for the following reasons:
Groups I and II lack unity of invention because even though the inventions of these groups require the technical feature of a CAR bridging protein comprising a CAR-binding domain and an antigen-binding domain, this technical feature is not a special technical feature as it does not make a contribution over the prior art in view of US 20150307564, published October 29, 2015 (see instant PTO-892), which teaches chimeric antigen receptor effector cell switches comprising an antigen that binds a CAR on an effector cell and a targeting moiety that binds a cell surface molecule on a target cell [0005], which reads on the bridging protein comprising a CAR-binding domain an antigen binding domain.
During a telephone conversation with Amanda Schnepp on November 13, 2025 a provisional election was made without traverse to prosecute the invention of group I, claims 30-31, 33-34, 37, 40, 42, 44, 50, 55-56, 59-60, 62, 65, 67, 69-70, and 76. Affirmation of this election must be made by applicant in replying to this Office action. Claim 78 is withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected invention.
Applicant is reminded that upon the cancelation of claims to a non-elected invention, the inventorship must be corrected in compliance with 37 CFR 1.48(a) if one or more of the currently named inventors is no longer an inventor of at least one claim remaining in the application. A request to correct inventorship under 37 CFR 1.48(a) must be accompanied by an application data sheet in accordance with 37 CFR 1.76 that identifies each inventor by his or her legal name and by the processing fee required under 37 CFR 1.17(i).
The examiner has required restriction between product or apparatus claims and process claims. Where applicant elects claims directed to the product/apparatus, and all product/apparatus claims are subsequently found allowable, withdrawn process claims that include all the limitations of the allowable product/apparatus claims should be considered for rejoinder. All claims directed to a nonelected process invention must include all the limitations of an allowable product/apparatus claim for that process invention to be rejoined.
In the event of rejoinder, the requirement for restriction between the product/apparatus claims and the rejoined process claims will be withdrawn, and the rejoined process claims will be fully examined for patentability in accordance with 37 CFR 1.104. Thus, to be allowable, the rejoined claims must meet all criteria for patentability including the requirements of 35 U.S.C. 101, 102, 103 and 112. Until all claims to the elected product/apparatus are found allowable, an otherwise proper restriction requirement between product/apparatus claims and process claims may be maintained. Withdrawn process claims that are not commensurate in scope with an allowable product/apparatus claim will not be rejoined. See MPEP § 821.04. Additionally, in order for rejoinder to occur, applicant is advised that the process claims should be amended during prosecution to require the limitations of the product/apparatus claims. Failure to do so may result in no rejoinder. Further, note that the prohibition against double patenting rejections of 35 U.S.C. 121 does not apply where the restriction requirement is withdrawn by the examiner before the patent issues. See MPEP § 804.01.
Claims 30-31, 33-34, 37, 40, 42, 44, 50, 55-56, 59-60, 62, 65, 67, 69-70, and 76 are under consideration in this office action.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. The application is the national stage entry of PCT/IB2021/000358, which claims benefit to U.S. Provisional Application No. 63/030,653, filed May 27, 2020.
Information Disclosure Statement
The information disclosure statements (IDSs) submitted on November 23, 2022 and May 28, 2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the IDSs are being considered by the examiner.
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Claim Objections
Claims 50 and 67 are objected to because of the following informalities:
Claim 50 (line 5) uses the abbreviation “FcgR” without first defining what it represents. While claims can reference abbreviations, the material presented by the abbreviation must be clearly set forth at the first use. Also, the term “receptors” after FcgR is unnecessary.
In claim 67, an amino acid sequence directed to a linker comprising the sequence of GGGS is not identified by a sequence identifier. This sequence is clearly identified as SEQ ID NO: 7 in the specification (pg 3, 4, 17, and 19). Applicant is required to add this sequence identifier to the claim.
Appropriate correction is required.
Recommendations
Claims 34, 40, 42, 44, 50, 60, 62, and 76 use the word “optionally”. Applicant is advised that limitations after “optionally” do not have patentable weight. Review and confirm that the usage of the term was intentional.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 37, 40, 50, and 56 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 37 recites the limitation "the extracellular portion" in lines 3, 4, and 5 and “the antigen-binding portion of an antibody”. This claim depends from claim 30, which does not include an extracellular portion limitation or antigen-binding portion limitation. There is insufficient antecedent basis for these limitation in the claim.
Claim 40 recites the limitation "the target". This claim depends from claim 30, which does not include a target limitation. There is insufficient antecedent basis for this limitation in the claim.
Claim 50 recites the limitation the “the wild-type human heavy chain Fc domain". This claim depends from claim 34, which does not include a wild-type limitation. There is insufficient antecedent basis for this limitation in the claim.
Claim 56 recites the limitations "the antigen of interest" in lines 1 and 2. This claim depends from claim 30, which does not include an antigen of interest limitation. Also, there is no mention of antigen of interest in the preamble of the claim. There is insufficient antecedent basis for these limitations in the claim.
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 30-31, 33-34, 37, 40, 42, 44, 50, 55-56, 59-60, 62, 65, 67, 69-70, and 76 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 contain subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
“[T]he purpose of the written description requirement is to ‘ensure that the scope of the right to exclude, as set forth in the claims, does not overreach the scope of the inventor’s contribution to the field of art as described in the patent specification.’” Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1353-54 (Fed. Cir. 2010) (en banc) (quoting Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 920 (Fed. Cir. 2004)). To satisfy the written description requirement, the specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1562-63, 19 USPQ2d 1111 (Fed. Cir. 1991). See also MPEP 2163.04.
Claims 30-31, 33-34, 37, 40, 42, 44, 50, 55-56, 59-60, 62, 65, 67, and 69 are directed to a CAR bridging protein comprising a CAR-binding domain and an antigen-binding domain. Claims 70 and 76 are directed to nucleic acid molecules and pharmaceutical compositions of the CAR bridging protein. These claims are directed to a broad genus of CAR bridging proteins, and the CAR bridging proteins are not described sufficiently to show that applicant had possession of the claimed invention.
The antigen-binding domain and the CAR-binding domain include domains of a wide variety of structures, including peptide ligands and antibodies. The CAR-binding domain may be comprised of the antigen-binding portion of an antibody, a ligand that interacts with the extracellular portion of a CAR, a portion of an HIV-1 gp120 protein, or a portion of a CD19 protein (Spec, pg 3-4, 8). The antigen-binding domain may be comprised of an antigen-binding domain of an antibody that recognizes a tumor antigen or a viral antigen or a portion of an ACE2 extracellular domain that binds to coronavirus spike protein (Spec, pg 3-4, 7. Because there is no consistent structure for the CAR bridging protein, the claims are directed to proteins defined almost entirely by function, i.e. to what they bind. Although the CAR-binding domain is identified as HIV-1 gp120 in claim 44 and the antigen-binding domain is identified as a portion of an ACE extracellular domain in claim 62, the other domain in each of these claims is left completely undefined, and, thus, claims 44 and 62 are included in this rejection for failing to meet the written description requirement.
For claims drawn to a genus, a generic statement that defines a genus of substances by only their functional activity does not provide an adequate written description of the genus. Reagents of the University of California v. Eli Lilly, 43 USPQ2d 1398 (CAFC 1997).
"A written description of an invention involving a chemical genus, like a description of a chemical species, 'requires a precise definition, such as by structure, formula, [or] chemical name,' of the claimed subject matter sufficient to distinguish it from other materials." Fiers, 984 F.2d at 1171, 25 USPQ2d 1601; In re Smythe, 480 F.2d 1376, 1383, 178 USPQ 279, 284985 (CCPA 1973) ("In other cases, particularly but not necessarily, chemical cases, where there is unpredictability in performance of certain species or subcombinations other than those specifically enumerated, one skilled in the art may be found not to have been placed in possession of a genus ...") Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
The recitation of a functional property alone, which must be shared by the members of the genus, is merely descriptive of what the members of the genus must be capable of doing, not of the substance and structure of the members. Agents described by function alone are not special and are not excluded from the written description requirement. As was held in University, Rochester v G.D. Searle Co., 358 F.3d 916 (Fed. Cir. 2004), a functional genus cannot be described by a method of obtaining or screening for the agent that meets the functional limitations of the claim.
The description requirement of the patent statute requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736, F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming rejection because the specification does "little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate.") Accordingly, it is deemed that the specification fails to provide adequate written description for the genus of the claims and does not reasonably convey to one skilled in the relevant art that the inventor(s), at the time the application was filed, had possession of the entire scope of the claimed invention.
Here, though the CAR bridging protein is comprised of CAR and antigen binding domains, the claims lack written description because there is no disclosure of a correlation between function and structure of the CAR bridging protein beyond those disclosed in the examples in the specification. Although the specification provides multiple examples of CAR bridging protein, these examples lack sufficient variety to reflect the broad the genera of the two domains.
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 claimed genus. See MPEP 2163 II.A.3a.ii.
With respect to product claims, it is recognized that information which is well known in the art need not be described in detail in the specification (MPEP 2163 II.A.2). See, e.g., Hybritech, Inc. v. Monoclonal Antibodies, Inc., 802 F.2d 1367, 1379-80, 231 USPQ 81, 90 (Fed. Cir. 1986). However, sufficient information must be provided to show that the inventor had possession of the invention as claimed.
In the instant case, the CAR binding domain and antigen binding domain may comprise antibodies. While the prior art teaches some understanding of the structural basis of antigen-antibody recognition, it is noted that the art is characterized by a high level of unpredictability, since the skilled artisan still cannot accurately and reliably predict the consequences of amino acid substitutions, insertions, and deletions in the antigen-binding domains. Antibodies generally share certain characteristics such as Fc regions or hinge regions. However, these structures are not correlated with the binding function of the antibody. It is well established in the art that the formation of an intact antigen-binding site generally requires the association of the complete heavy and light chain variable regions of a given antibody, each of which consists of three complementarity determining regions (CDRs) that provide the majority of the contact residues for the binding of the antibody to its target epitope. The amino acid sequences and conformations of each of the heavy and light chain CDRs are critical in maintaining the antigen binding specificity and affinity, which is characteristic of the immunoglobulin. It is expected that all of the heavy and light chain CDRs in their proper order and in the context of framework sequences, which maintain their required conformation, are required in order to produce a protein having antigen-binding function and that proper association of heavy and light chain variable regions is required in order to form functional antigen binding sites (see Almagro et al, Section 3 “Antibody Structure and the Antigen Binding Site” and Figure 1; PTO-892).
In the instant case, the specification provides insufficient direction or guidance concerning the relationship between the structure of the possible antibody or antigen-binding fragment thereof to demonstrate possession of the breadth of the genus of antibodies encompassed by the instant claims, especially in view of the unpredictability of such an endeavor. The prior art, as evidenced by Edwards et al., 2003 (instant PTO-892), teaches there is a substantially huge antibody diversity produced to one single antigen target. Edwards provides evidence that over 1000 antibodies, all different amino acid sequences, were generated towards one single protein antigen target (see abstract). Without a correlation between structure and function, the claims do little more than define the claimed invention by function. That is not sufficient to satisfy the written description requirement. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406 (“definition by function … does not suffice to define the genus because it is only an indication of what the gene does, rather than what it is”).
To provide adequate written description and evidence of possession of the claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, or any combination thereof. In the instant case, the only factors present in the claims are a recitation of one generic, broad genus that encompassed a diverse and huge number of possible antibodies, peptides, and other agents that bind the desired epitope. The specification does not provide a consistent structure for all of the possible antibodies and other agents and fails to provide a representative number of species for the claimed 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 of the elements 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 a few species within the genus of CAR-binding peptide or antigen-binding peptide.
The written description requirement is to ‘ensure that the scope of the right to exclude, as set forth in the claims, does not overreach the scope of the inventor’s contribution to the field of art as described in the patent specification. Applicant has not described the CAR briding protein of the invention sufficiently to meet this requirement.
With the exception of specifically disclosed antibodies with specific CDRs or well-known proteins with well-understood binding partners, the skilled artisan cannot envision the detailed chemical structure of all of the encompassed CAR-briding proteins, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The product itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016.
One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481 at 1483. In Fiddes, claims directed to mammalian FGF's were found to be unpatentable due to lack of written description for that broad class. Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. §112 is severable from its enablement provision (see page 1115).
Therefore, claims 30-31, 33-34, 37, 40, 42, 44, 50, 55-56, 59-60, 62, 65, 67, 69-70, and 76 do not meet the written description requirement.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 30, 33, 37, 42, and 55-56 are rejected under 35 U.S.C. 102(1)(a) as being anticipated by Feldman et al, published November 13, 2019 (instant PTO-892).
Feldman et al teaches a novel CAR platform technology termed RevCAR system where the CARs expressed on the T cells lack the scFv; instead, the extracellular portion of the CAR comprises a small peptide epitope (ln 5-8). Only when in the presence of a corresponding bispecific antibody-based target module (revTM) can the RevCAR T cells be redirected to tumor cells (ln 9-12). The bispecific antibody comprises a CAR-binding domain and an antigen-binding domain, which reads on the CAR bridging protein of instant claim 30. Also, this bispecific antibody reads on the CAR bridging protein directed to a CAR-binding domain that binds the extracellular portion of a CAR of claim 37 and the CAR bridging protein comprised of a CAR-binding domain comprising an antibody or antigen binding fragment thereof of instant claim 42. The bispecific antibody is a fusion protein, which reads on instant claim 33. Feldman et al teaches that the RevCAR system can be adapted to any tumor antigen, which reads on the antigen-binding domain limitations of instant claims 55-56.
Feldman anticipates claims 30, 33, 37, 42, and 55-56
Claims 30-31, 33-34, 37, 40, 50, 55-56, 59, 65, 67, 69-70, and 76 are rejected under 35 U.S.C. 102(a)(1) and 102 (a)(2) as being anticipated by US 20150307564, published October 29, 2015 (“Young”; see instant PTO-892).
Young teaches CAR-effector cell switches comprised of a peptide antigen that binds a CAR on an effector cell (i.e. CAR binding peptide) and a targeting moiety that binds a cell surface molecule on a target (i.e. targeting polypeptide) ([0024], [0036]), which reads on the CAR bridging protein comprised of a CAR binding domain and an antigen binding domain of instant claim 30. The targeting moiety of the CAR-effector cell switch may be conjugated to a linker to create a small molecule-linker intermediate, which may react with a reactive functional group on the CAR binding peptide [0081]-[0082], which reads on the chemically conjugated antigen-binding domain of instant claim 31.
Young teaches that the CAR-binding protein is fused to the targeting polypeptide [0024], which reads on the fusion protein of instant claim 33.
The CAR-effector switch of Young may further comprise the Fc region [0027], which reads on instant claim 34. The targeting antibody may be human, which reads on the human Fc domain of instant claim 50.
Young teaches that the CAR-binding protein is a peptidic antigen that binds a CAR on an effector cell [0037], which reads on the peptide that interacts with the extracellular portion of a CAR of instant claim 37.
The CAR binding domain of Young is bound by a CAR [0043]; for example, the CAR-binding domain may be yeast transcription factor GCN4 that binds a specific scFv that recognizes GCN4 (figure 2), which reads on instant claim 40.
Young teaches that the antigen-binding domain of the CAR-effector cell switch may target Her2-positive cancer cells ([0056], [0067]), which reads on tumor antigen of instant claim 55.
The targeting moiety of Young (i.e. the antigen binding domain) may comprise an anti-CD19 antibody, which reads on the limitation of claim 56 directed to an antigen-binding domain that interacts with an antigen of interest and the limitation of claim 59 directed to an antigen-binding domain that binds CD19.
Young teaches a linker comprised of the amino acid sequence GGGGS, which reads on the linker of instant claims 65 and 67. The CAR-effector switch of Young is be a homodimer (as shown in Figure 6), which reads on instant claim 69.
Young teaches polypeptide and nucleic acid pharmaceutical compositions for the CAR switch proteins [0153], which reads on instant claims 70 and 76.
Young anticipates claims 30-31, 33-34, 37, 40, 50, 55-56, 59, 65, 67, 69-70, and 76.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 30-31, 33-34, 37, 40, 44, 50, 55-56, 59, 65, 67, 69-70, and 76 are rejected under 35 U.S.C. 103 as being unpatentable over US 20150307564, published October 29, 2015 (“Young”) in view of Seif et al, published November 2019 (instant PTO-892).
The teachings of Young are discussed above. Young also teaches that the peptidic antigen may be a peptide ligand [0043]. Young does not teach a CAR bridging protein wherein the CAR-binding domain comprises a portion of an HIV-1 gp120 protein.
Seif et al teaches CD4-based CARs that bind the envelope protein gp120 of HIV and the utility of CAR-transduced T cells (CAR-T cells) in the treatment of HIV infection (pg 3, column 2).
Based on the disclosure of Young and the CAR that binds gp120 of Seif et al, it would have been obvious to one of ordinary skill in the art to prepare the CAR bridging protein of Young with the gp120, because this target was already known in the art to bind specifically to CD4 CARS. The artisan would have been motivated to try and use gp120 in this way and have a reasonable expectation of success because of the prior teachings of Young, which teaches a CAR bridging protein comprised of CAR binding protein. It would have been obvious to replace the CAR binding protein of Young with another peptide known to target CD40 CAR T cells, because one of ordinary skill in the art would have been able to carry out such a substitution, and the results were reasonably predictable. As is stated in MPEP §2144.06, substituting one equivalent element for another known for the same purpose renders an invention obvious and an “express suggestion to substitute one equivalent component or process for another is not necessary to render such substitution obvious. In re Fout, 675 F.2d 297, 213 USPQ 532 (CCPA 1982)." Substituting one known element for another to yield predictable results does not meet the threshold for a prima facie case of nonobviousness, absent convincing evidence to the contrary.
Claims 30-31, 33-34, 37, 40, 50, 55-56, 59-60, 65, 67, 69-70, and 76 are rejected under 35 U.S.C. 103 as being unpatentable over US 20150307564, published October 29, 2015 (“Young”) in view of Seif et al, published November 2019 (instant PTO-892), as applied to claims 30-31, 33-34, 37, 40, 44, 50, 55-56, 59, 65, 67, 69-70, and 76 above, and further in view of Oh et al, published October 2011 (instant PTO-892).
The teachings of Young in view of Seif et al are discussed above. In addition, Seif et al teaches the general utility of CAR T cell therapy for infectious diseases due to various viruses (abstract). For example, T cells have been engineered with HIV envelope-binding domains to form anti-HIV CAR T cells (pg 3, column 2, ln 1-3). Because CAR-T therapy has been successfully used to treat viral infections by binding to viral envelope proteins and the well-known role pathogenic-specific T cells play in the presentation of infectious disease, it would have been obvious to the ordinary artisan that this method could be applied to other viral infection, such as a coronavirus. Young in view of Seif et al, however, does not specifically teach a CAR bridging protein wherein the antigen-binding domain binds to coronavirus spike protein.
Oh et al teaches that T cells play an important role in viral clearance during a primary infection of SARS-CoV; indeed, SARS-specific memory T cell responses against the spike protein are present in SARS recovered patients (pg 10464, column 1). Oh et al teaches that CAR-T cells can be redirected to target the coronavirus responsible for severe acute respiratory syndrome (SARS) (abstract). Cytotoxic T-lymphocyte epitopes have been identified for the spike protein (pg 10464, column 1).
Given that Young in view of Seif et al teach the treatment of viral infections with a CAR bridging protein and further given that Oh et al teaches CAR-T cells that target the spike protein of SARS-CoV, it would have been obvious to the ordinary artisan to pursue a CAR bridging protein capable of binding a coronavirus spike protein, as required by instant claim 60. The motivation to do so comes from Oh et al, which teaches that SARS-specific TCR-redirected T cells can provide prophylactic or therapeutic opportunities against this life-threatening infection (pg 10464, column 2; pg 10471, column 1).
Claims 30-31, 33-34, 37, 40, 50, 55-56, 59-60, 62, 65, 67, 69-70, and 76 are rejected under 35 U.S.C. 103 as being unpatentable over US 20150307564, published October 29, 2015 (“Young”) in view of Seif et al, published November 2019 and Oh et al, published October 2011, as applied to claims 30-31, 33-34, 37, 40, 50, 55-56, 59-60, 65, 67, 69-70, and 76 above, and further in view of Lan et al et al, published March 30, 2020 (instant PTO-892).
The teachings of Young in view of Seif et al and Oh et al are discussed above. This combination of references does not teach a CAR bridging domain comprising an antigen-binding domain comprising at least a portion of an ACE2 extracellular domain, as required by instant claim 62.
Lan et al teaches that binding of the receptor-binding domain of the spike protein of SARS-Cov-2 to its receptor ACE2 is the initial step of infection (abstract).
Given that Young in view of Seif et al and Oh et al teach a CAR bridging protein with an antigen-binding domain that recognizes coronavirus spike protein and further given that Lan et al teach that the spike protein of SARS-CoV-2 binds to ACE, it would have been obvious to the ordinary artisan to pursue a CAR bridging protein comprised of an ACE2 extracellular to bind a coronavirus spike protein, as required by instant claim 62. The motivation to do so comes from Oh et al, which teaches that SARS-specific TCR-redirected T cells can provide prophylactic or therapeutic opportunities against this life-threatening infection (pg 10464, column 2; pg 10471, column 1).
As is stated in MPEP §2144.06, substituting one equivalent element for another known for the same purpose (e.g., ACE2 of Lan et al for the gp120 of Young in view of Seif et al for treating viral infection) renders an invention obvious and an “express suggestion to substitute one equivalent component or process for another is not necessary to render such substitution obvious. In re Fout, 675 F.2d 297, 213 USPQ 532 (CCPA 1982)."
Conclusion
No claim is allowed.
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Jennifer Benavides
Examiner
Art Unit 1675
/JENNIFER A BENAVIDES/Examiner, Art Unit 1675