DETAILED ACTION
Status of Application, Amendments and/or Claims
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
The amendment of 4/13/26 has been entered in full. Claims 11, 13-14, 16, 23, 28-35, 37-38 and 45 are amended. Claims 82, 91-92, 97 and 139 are canceled. Claims 1-17, 19, 22-23, 26-38 and 45 are pending.
Election/Restrictions
Applicants' election without traverse of Group I, currently all pending claims, in the reply filed on 4/13/26 is acknowledged. Applicant has canceled the claims of non-elected Groups II and III. The elections of the following species are also acknowledged:
(1) For gating adaptor, the species that comprises fluorescein as the first moiety (claim 17) and acetazolamide as the second moiety (claim 19). Applicants indicate that claims 1-8, 12-17, 19, 26-30, 33-38 and 45 read on the elected species.
(2) For targeting adaptor, the species that comprises a first LBD (tLBD-1) antibody that targets a cell-surface antigen that is CD19; and a second LBD (tLBD-2) that comprises CA9. Applicants indicate that claims 1-3, 5-6, 8, 12-17, 19, 26-30, 33-38 and 45 read on the elected species. However, claim 8 is directed to a tLBD-2 that is an antibody, which does not encompass the elected species having CA9 as the tLBD-2.
(3) For chimeric receptor, the species that comprises an antibody as the type of extracellular ligand bind domain (rLBD) structure, and fluorescein as the type of gating adaptor target that the rLBD is specific for. Applicants indicate that claims 1-3, 5-6, 8, 12-17, 19, 26-30, 33-38 and 45 read on the elected species.
Claims 4, 7-11 and 22-23 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim.
Claims 1-3, 5-6, 12-17, 19, 26-30, 38 and 45 are under consideration, as they read on each of the elected species.
Specification
The disclosure is objected to for the following informalities:
---The term “adaptor” is misspelled as “adapter” in 40 instances; specifically, in the Title and in each instance in ¶ 84-92 (published application). Compare with the usage through the remainder of the specification, e.g., at ¶ 9-12.
---The title of the invention is not descriptive, because it is directed solely to a receptor, whereas the claims are directed a system. A new title is required that is clearly indicative of the invention to which the claims are directed. The following title is suggested: “Gated Adaptor Targeting Receptor System”.
Appropriate correction is required.
Claim Objections
Claims 27 and 35 are objected to because of the following informalities:
Claim 27 is objected to because it is recites an “…an scFv sequence according to (1) SEQ ID NO: 2, (ii) SEQ ID NO: 30…” However, an alignment of SEQ ID NO: 2 and 30 indicates that these two sequences, which are each 254 amino acids in length, are 100% identical. As such, the recitation of each in claim 27 is objected to as redundant; one should be removed from the claim.
In claim 35, the term “CD4” redundantly appears in each of lines 2 and 3.
In claim 35, the term “carcinoembryonic antigen (DEA)” appears twice in line 5.
In claim 35, lines 8 and 9, “EGFR” and “epidermal growth factor receptor (EGFR)” each refer to the same protein and thus are redundant.
In claim 35, line 13, “FDVTW- MAA” should be “FDVTW-MAA”.
In claim 35, line 20, “MUC -1” should be “MUC-1”.
In claim 35, line 22, “antigen -1” should be “antigen-1”.
The remaining claim(s) are objected to for depending from an objected claim.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 35 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention.
Claim 35 further limits the cell-surface antigen (CSA) to one selected from a group including the following terms that are indefinite:
---In line 12, the terms “HER1-HER2” and “HER2-HER3 in combination” are indefinite because the CSA is singular, but each of these elements are directed to two antigens (plural).
---In line 15, the terms “kappa chain” and “lambda chain” are indefinite because these are the terms for two types of antibody light chains rather than a specific CSA.
---In line 23, the term “surviving and telomerase” is unclear as to what antigen is being referred to because (1) “surviving” is a verb rather than a noun, and (2) telomerase is an intracellular enzyme rather than a CSA.
---In line 24, the terms “the extra domain A (EDA) and extra domain B (EDB) of fibronectin” is indefinite because the recited group is directed to “the cell-surface antigen”, which is singular, but each this element is directed to two antigens (plural).
Claim Rejections - 35 USC § 112(a), written description
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 1-3, 5-6, 12-17, 19, 26-30, 38 and 45 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
Per MPEP 2163, 35 U.S.C. 112(a) requires, “separate and distinct from the enablement requirement”, that the “specification shall contain a written description of the invention…” (Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1355 (Fed. Cir. 2010)). In making a determination of whether the application complies with the written description requirement of 35 U.S.C. 112(a), it is necessary to understand what Applicants are claiming and what Applicants have possession of.
The instant claims are directed to a product; specifically, a system having at least three parts: (1) a gating adaptor; (2) a targeting adaptor that comprises a first ligand binding domain (tLBD-1) that is specific for a cell surface antigen (CSA), and a second LBD (tLBD-2) that is specific for the gating adaptor (or vector encoding such); and (3) an engineered immune cell comprising a chimeric receptor (or vector encoding such) comprising an extracellular LBD (rLBD) specific for the gating adaptor, a transmembrane domain, and an intracellular actuator domain. The elected species of gating adaptor under consideration is one that comprises the small molecules fluorescein (as first moiety) and acetazolamide (as second moiety). The elected species of targeting adaptor under consideration is one that has a tLBD-1 that is an anti-CD19 antibody, and a tLBD-2 that comprises CA9 (the enzyme carbonic anhydrase 9). The elected species of chimeric receptor under consideration is one that comprises an anti-fluorescein antibody. Considered as a whole, the claimed system encompasses a genus of parts, because each of the three parts, each directed to a subgenus of molecules having different structures.
In the broadest claims, e.g., independent claim 1, only the chimeric receptor has any type of defined structure, as a receptor is a type of polypeptide, and the other two parts encompass any type of structure.
More specifically, the term “gating adaptor” is defined by the instant specification only as “any moiety capable of being specifically recognized by a receptor, such as a chimeric receptor or the like” (¶ 88, published application). Independent claim 1 further requires that one of the ligand-binding domains is “specific” for the gating adaptor, indicating that the gating adaptor must also be capable of being specifically recognized by the targeting adaptor. Thus, the “gating adaptor” is defined by the specification and claims solely by its functionality with respect to the receptor and targeting adaptor of the system, i.e., being able to be bound by a receptor. No particular structure is denoted by the term. Thus, the gating receptor broadly encompasses any compound or compounds to which an antibody, protein or other molecule can bind. While the elected species of gating adaptor encompasses a small molecule comprising two moieties (fluorescein and acetazolamide), the gating adaptor broadly encompasses all types of structures, including other small molecules, antibodies, proteins, peptides, carbohydrates, lipids, inorganic molecules and more.
The term “targeting adaptor” is not further defined by the instant specification beyond what is recited in independent claim 1; i.e., a compound comprising two ligand binding domains, one specific for a cell-surface antigen, and one specific for the gating adaptor. No specific structure is denoted by the term. Thus, the gating receptor also broadly encompasses all types of structures, and is only defined by its functional activity; i.e., its ability to bind to a cell surface antigen and the gating adaptor.
Thus, the claimed system encompasses both a receptor and a targeting adaptor that can bind to the gating adaptor. Examples of gating adaptors are given that include 18 different compounds (recited in the alternative in claims 17 and 19). Thus, the claims encompasses a genus of receptors that bind to each of these compounds, and a genus of targeting adaptors that bind to each of these compounds.
The elected species of receptor is one that comprises an antibody that binds to fluorescein. While the general structure of an antibody was well-known in the prior art, it is the structure of the complementarity-determining regions (CDRs) that determines the specificity of a particular antibody, and said CDR structure is not predictable based on the epitope to which it binds. Thus, even knowing the structure (CDRs) of one antibody does not allow the skilled artisan to predict the structure of other antibodies that bind to the same epitope or to the other epitopes. The relevant art, Ferrara et al (2015. mAbs. 7(1): 32-41) teaches that there is substantial variation in the structure of antibodies that bind to a single protein, on the order of hundreds of different sequences; specifically, see page 36: "The number of different HCDR3s selected against the test antigens ranges from 74 to 460 (Table 3), with the actual number of different antibodies likely to be significantly higher when different VL chains and additional VH mutations are taken into account” (pg 36).
Thus, the claims are genus claims because they encompass use of a genus of receptors with the required functionality, i.e., binding to fluorescein. However, a product defined by function is not in and of itself sufficient to describe the product because it is only an indication of what the product does, rather than what it is; i.e., the specific structure of the product. It is only a definition of a useful result rather than a definition of what achieves that result. Per MPEP 2124, "describing a composition by its function alone typically will not suffice to sufficiently describe the composition". Furthermore, in the instant case the specification does not establish a correlation between structure and function; i.e., the structure of one anti-fluorescein antibody does not provide predictability regarding other antibody structures having the same functionality. Furthermore, the decision of the Federal Circuit in Amgen v. Sanofi, 872 F.3d 1367 (Fed. Circ. 2017) held that a claim directed to an antibody requires written description of the antibody itself rather than being satisfied solely by a written description of the antigen to which it binds (the so-called "newly characterized antigen" test). Thus, a description of the target protein (e.g. fluorescein) is not in and of itself sufficient to provide a description of the genus of antibodies binding to said target.
Written description for a genus may also be satisfied through sufficient description of a relevant number of species. This is dependent on whether one of skill in the art would recognize necessary common attributes or features possessed by the members of the genus. Generally, in an unpredictable art, adequate description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus. Also, “[w]hen a patent claims a genus using functional language to define a desired result, the specification must demonstrate that the applicant has made a generic invention that achieves the claimed result and do so by showing that the applicant has invented species sufficient to support a claim to the functionally-defined genus" (Capon v. Eshhar, 418 F.3d 1349 (Fed. Cir. 2005)). “[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).
In support of the genus of antibodies binding to fluorescein, the specification provides a single example of an antibody structure that is defined by its CDRs (as recited in claim 27, which is also termed E2 in the specification. As such, what is disclosed (a single unique set of CDRs comprised by an antibody structure) does not correspond in scope to that which is claimed (the genus of anti-fluorescein antibodies, which includes at least hundreds of sequences). Per MPEP 2163, "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 AbbVie 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."). As such, in the instant case the specification does not provide a representative number of species of the genus of antibodies that can bind to fluorescein.
Turning to the larger genus of receptors encompassed by the claims, the specification does not provide examples of antibody structures that can bind to each of other 18 molecules that are given as examples of gating adaptors, i.e., folate, acetazolamide, CA9, tacrolimus, etc (as recited in claims 17 and 19). Furthermore, the claimed receptors encompass antibodies that bind to any other type of encompassed gating adaptor structure, as well as other types of receptor structures, e.g., extracellular ligand binding domains that bind to each of the possible gating adaptor structures, but the specification does not provide any specific examples of such protein structures. Thus, the specification does not provide a description of the structure of the claimed receptors that corresponds in scope to that which is claimed; i.e., a genus of receptors defined by functionality.
With respect to the targeting adaptor, the specification provides a long list of potential cell-surface antigens to which the adaptor can bind (as recited in claim 35), but provide only a single specific example of a specific antibody structure that targets a specific cell-surface antigen; specifically, an scFv sequence (SEQ ID NO: 52) that binds to the cell-surface antigen CD19. The specification further provides only two specific examples of ligand-binding domains that target the gating adaptor; specifically, the elected species of CA9 enzyme (SEQ ID NO: 20) that can bind to acetazolamide, and the non-elected species of folate receptor domain (SEQ ID NO: 18) that can bind to folate.
Thus, the specification envisions a structurally diverse genus of gating adaptors, target adaptors, and receptors, defined primarily by their functionality (binding to particular targets), but fails to describe with specificity a representative number of examples corresponding in scope to the genus. The specification fails to describe what changes can be made to the disclosed species to produce species having different structures and still retain the required functionality. As such, the specification fails to disclose relevant identifying characteristics sufficient to describe the claimed invention in such full, clear, concise, and exact terms that a skilled artisan would recognize applicant was in possession of the claimed invention.
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111 (Fed. Cir. 1991), clearly states “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” (pg 1117). The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed” (pg 1116).
For these reasons, only a Gated Adaptor Targeting Receptor (GATR) system, comprising (a) a gating adaptor comprising a first moiety that is fluorescein and a second moiety that is acetazolamide; (b) a targeting adaptor comprising a first ligand binding domain (tLBD-1) that comprises an anti-CD19 antibody of SEQ ID NO: 37 and a and second ligand binding domain (tLBD-2) that comprises a CA9 domain of SEQ ID NO: 20, or a vector encoding said targeting adaptor; and (c) an engineered immune cell comprising a chimeric receptor that comprises an extracellular ligand-binding domain (rLBD) that is an antibody specific for fluorescein and comprises the CDRs of SEQ ID NO: 99-104, a transmembrane domain, and an intracellular actuator domain, or a vector encoding said chimeric receptor, but not the full breadth of claim 54 meets the written description provision of 35 U.S.C. §112(a). Applicants are reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. §112 is severable from its enablement provision (pg 1115).
Conclusion
No claims are allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ZACHARY C HOWARD whose telephone number is (571)272-2877. The examiner can normally be reached on Monday to Friday from 9 AM to 5 PM. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Vanessa Ford, can be reached at telephone number (571) 272-0857. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ZACHARY C HOWARD/Primary Examiner, Art Unit 1674
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