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 5/20/2024, is acknowledged.
Claims 3-6, 8-10, 13-16, 18-20, 24-26, 28, 31-33, 35, 39, 41-43, 45-54, 56, 57, 59, 60, 63-68, 70-72, and 74-85 are cancelled.
Claims 1, 2, 7, 11, 12, 17, 31-23, 27, 29, 30, 34, 36-38, 40, 44, 55, 58, 61, 62, 69, and 73 are currently pending.
Claims 1 is an independent claim.
Election/Restrictions
Applicant’s election of Group I, claims 1, 2, 7, 11, 12, 17, 31-23, 27, 29, 30, 34, 36-38; and claims 58 and 61 in part, drawn to a chimeric receptor; and the species of: i) a human cell; ii) CD19 as the target; and iii) the chimeric polypeptide sequence of SEQ ID NO: 106 in the reply filed on 6/16/2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claim 11 is drawn to an unelected species of extracellular binding domain (i.e., a receptor ligand and not a scFv).
Claims 27, 29 and 30 are drawn to unelected species of chimeric polypeptide intracellular domains (i.e., ICDs with signaling domains).
Claims 11, 27, 29, 30, 40, 44, 55, 62, 69, and 73 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to nonelected inventions and/or species.
After consideration, the search and examination for the DNA binding domains (claim 36) and TAD domains (claim 37) has been extended to cover the unelected species as well.
Claims 1, 2, 7, 12, 17, 21-23, 34, 36-38, 58, and 61 are under examination as reading on a chimeric polypeptide comprising an extracellular ligand binding domain, a linking polypeptide, a TM domain, and an ICD.
Claim 1 in an independent claim.
Priority
Applicant’s claim for the benefit of a prior-filed U.S. Provisional Application No. 63/165,525, filed March 24, 2021, is acknowledged.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 12/16/2025 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner in its entirety.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency 1 – Nucleotide and/or amino acid sequences appearing in the drawings are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). Sequence identifiers for nucleotide and/or amino acid sequences must appear either in the drawings or in the Brief Description of the Drawings.
Specifically, sequences are disclosed in Fig. 1A without the corresponding sequence identifiers either in the figure or in the Brief Description of the Drawings.
Required response – Applicant must provide:
Replacement and annotated drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers;
AND/OR
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers into the Brief Description of the Drawings, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
PLEASE NOTE: It is recommended to amend the specification to insert the required sequence identifiers into the Brief Description of the Drawings to overcome this issue.
Specific deficiency 2 – Nucleotide and/or amino acid sequences appearing in the specification are not identified by sequence identifiers in accordance with 37 CFR 1.821(d).
Specifically, sequences are disclosed in ¶[0100], [0107], and [0141] without the corresponding sequence identifiers.
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Specifically, hyperlinks are disclosed in the specification in Tables 2 and 5. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
The use of the terms:
In-Fusion® (¶[0242]);
X-VIVO® (¶[0247], [0261]);
TransIT®-Lenti (¶[0248], [0262]); and
Dynabeads® (¶[248], [0262]);
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 Objections
Claims 58 and 61 are objected to under 37 CFR 1.75(c), as being of improper dependent form because a multiple dependent claim cannot depend from two sets of claims drawn to different features. In the instant case, the claims are drawn to a polypeptide and a recombinant nucleic acid, which are different features as demonstrated by these being drawn to different inventive Groups.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1, 2, 7, 12, 17, 21-23, 34, 36-38, 58, and 61 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 inventors, at the time the application was filed, had possession of the claimed invention.
Claims 1, 2, 7, 12, 17, 21-23, 34, 36-38, 58, and 61 encompass chimeric receptors comprising a broad genus of extracellular ligand binding domains with either no recited structure (claims 1, 2, 7, 12, 17, 21-23, 34, 36, 37, 58, and 61), or a partial structure at best (claim 38) and the function of “binding affinity for a ligand” (claims 1, 2, 17, 21-23, 34, 36-38, 58, and 61) or “binds to CD19” (claims 7 and 12).
Claims 1, 2, 7, 12, 17, 21-23, 34, 36-38, 58, and 61 encompass chimeric receptors comprising a broad genus of linking polypeptides with either no recited structure (claims 1, 2, 7, 12, 17, 21-23, 34, 36, 37, 58, and 61), or a partial structure at best (claim 38) and the function of “capable of promoting oligomer formation of the chimeric polypeptide via intermolecular disulfide bonding”.
Claims 1, 2, 7, 12, 17, 21-23, 34, 36-38, 58, and 61 additionally encompass chimeric receptors comprising a broad genus of transmembrane domains with either no recited structure (claims 1, 2, 7, 12, 17, 21, 23, 34, 36, 37, 58, and 61) or a partial structure at best (claims 22 and 28) and the function of “ligand-inducible proteolytic cleavage sites” and “extracellular ligand-binding domain induces cleavage at the one or more ligand-inducible proteolytic cleavage sites between the transcriptional regulator and the linking polypeptide”.
Claims 1, 2, 7, 12, 17, 21-23, 34, 36-38, 58, and 61 additionally encompass chimeric receptors with a broad genus of intracellular domains with either no recited structure (claims 1, 2, 7, 12, 17, 21-23, 34, 36, 37, 58, and 61) or a partial structure at best (claim 38) all with the function of “two or more human or humanized transcriptional regulators”.
Claim 38 is considered a partial structure due to the sequence variation in the elected species of polypeptide, SEQ ID NO: 106. The total number of variants of a polypeptide having a specific number of amino acid substitutions can be calculated from the formula:
N
!
*
19
A
N
-
A
!
A
!
Where N is the length in amino acids of the reference polypeptide and A is the number of allowed substitutions. For a polypeptide that is 760 residues in length with 152 (0.2 x 760) allowed substitutions, there would be
760
!
*
19
(
152
)
760
-
152
!
152
!
Which is approximately 2.6x10701 variants with the functions recited supra.
However, the specification fails to provide adequate written description support for a genus of chimeric receptors with a partial structure at best having the desired functional properties required to practice the claimed functions of “binding affinity for a ligand” or “binds to CD19”; “capable of promoting oligomer formation of the chimeric polypeptide via intermolecular disulfide bonding”; “ligand-inducible proteolytic cleavage sites” and “extracellular ligand-binding domain induces cleavage at the one or more ligand-inducible proteolytic cleavage sites between the transcriptional regulator and the linking polypeptide”; and “two or more human or humanized transcriptional regulators”.
The claims are not supported by a description that satisfies 35 U.S.C. § 112(a) or 35 U.S.C. § 112, first paragraph. "[T]he test for sufficiency [of the written description] is whether the disclosure of the application relied upon reasonably conveys to those skilled in the art that the inventor had possession of the claimed subject matter as of the filing date." Ariad Phanns., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1351 (Fed. Cir. 2010) (en bane).
A "sufficient description of a genus ... requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can 'visualize or recognize' the members of the genus." Id. at 1350. "[A]n adequate written description requires a precise definition, such as by structure, formula, chemical name, physical properties, or other properties, of species falling within the genus sufficient to distinguish the genus from other materials." Id.
"[F]unctional claim language can meet the written description requirement when the art has established a correlation between structure and function." Id. "But merely drawing a fence around the outer limits of a purported genus is not an adequate substitute for describing a variety of materials constituting the genus and showing that one has invented a genus and not just a species." Id.
"A sufficient description of a genus ... requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can "visualize or recognize" the members of the genus" (AbbVie, 759 F.3d at 1297, reiterating Eli Lilly, 119 F.3d at 1568-69) (emphasis added).
The specification discloses design of humanized synNotch receptors comprising two or more transcriptional regulators (¶[0004]): “[t]he present disclosure relates generally to chimeric antigen receptors (e.g., the synthetic Notch receptors disclosed herein) that contain two or more human or humanized transcriptional regulators to augment their function to regulate cell transcription”. The specification discloses that the synNotch receptors comprise an anti-CD19 or an anti-ALPPL2 scFv fused to an intracellular domain comprises different transcriptional regulators comprising DNA binding domains and a transactivation domain (Example 1, ¶[0242]): “…receptors were built by fusing an anti-CD19 scFv or an anti-ALPPL2 scFv to the corresponding receptor scaffold and intracellular tail…[r]eceptors were prepared to contain different intracellular domains (ICDs), including: a transcription factor DNA binding domain (DBD), such as various synthetic zinc finger proteins (based on a human-derived scaffold) or PAX6; a transcription factor transactivation domain (TAD), such as TADs of human p65, GR Tau1, p53, or ATF6; and an additional human transcriptional effector, such as TADs ofHSF-1, GATA3, p65, HIF1a, GR Tau1, ATF6, ELF3, or p53.” Specific examples of these chimeric receptors are disclosed in Tables 1, 2, 4, 5, and the Sequence Table.
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.).
Regarding the claimed chimeric receptors comprising a broadly claimed genus of extracellular ligand binding domains with a partial structure at best and the functions of “binding affinity for a ligand” or “binds to CD19” (claims 1, 2, 7, 12, 17, 21-23, 34, 36-38, 58, and 61), the claims are directed to a genus of chimeric receptors comprising extracellular ligand binding domains with a partial structure at best and the function of “binding affinity for a ligand” or “binds to CD19”, which includes antibody/scFv structures (see, for example, SEQ ID NO: 106). However, Federal Circuit clarification of the law of written description as it applies to antibodies. The U.S. Court of Appeals for the Federal Circuit (Federal Circuit) decided Amgen v. Sanofi, 872 F.3d 1367 (Fed. Cir. 2017), which concerned adequate written description for claims drawn to antibodies. The Federal Circuit explained in Amgen that when an antibody is claimed, 35 U.S.C. § 112(a) requires adequate written description of the antibody itself. Amgen, 872 F.3d at 1378-79. The Amgen court expressly stated that the so-called "newly characterized antigen" test, which had been based on an example in USPTO-issued training materials and was noted in dicta in several earlier Federal Circuit decisions, should not be used in determining whether there is adequate written description under 35 U.S.C. § 112(a) for a claim drawn to an antibody. Citing its decision in Ariad Pharmaceuticals, Inc. v. Eli Lilly & Co., the court also stressed that the "newly characterized antigen" test could not stand because it contradicted the quid pro quo of the patent system whereby one must describe an invention in order to obtain a patent. Amgen, 872 F.3d at 1378-79, quoting Ariad Pharmaceuticals, Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1345 (Fed. Cir. 2010). In view of the Amgen decision, adequate written description of a newly characterized antigen alone should not be considered adequate written description of a claimed antibody to that newly characterized antigen, even when preparation of such an antibody is routine and conventional.
In the instant case, the application is claiming chimeric receptors comprising extracellular domains that include antibodies. The instant specification only discloses two scFv structures (SEQ ID NO: 1 and 2), one which binds to CD19 and one which binds to ALPPL2. These limited number of structures do not sufficiently represent the broad genera of antigen binding constructs with differing CDR sequences that are encompassed by the claims.
Regarding the claimed chimeric receptors comprising a broadly claimed genus of linkers and the function of “capable of promoting oligomer formation of the chimeric polypeptide via intermolecular disulfide bonding” (claims 1, 2, 7, 12, 17, 21-23, 34, 36-38, 58, and 61), the instant specification discloses one truncated CD8α hinge domain (Tables 1 and 2, SEQ ID NO: 3) that has this function, which does not sufficiently represent the broad genera of linking polypeptides with differing sequences and the recited functions that are encompassed by the claims.
Regarding the claimed chimeric receptors comprising a broadly claimed genus TM domains with a partial structure at best and the functions of “ligand-inducible proteolytic cleavage sites” and “extracellular ligand-binding domain induces cleavage at the one or more ligand-inducible proteolytic cleavage sites between the transcriptional regulator and the linking polypeptide” (claims 1, 2, 7, 12, 17, 21-23, 34, 36-38, 58, and 61), the instant specification discloses TM domains comprising SEQ ID NO: 4 (i.e., the Notch1 TMD), and further comprising STS and RAM domains (¶[0019]-[0021], Sequence Table), with the functions recited in the claims. These 6 STS and 11 RAM sequences, combined with the one TM sequence do not sufficiently represent the broadly claimed genera of TM domains with a partial structure at best and the functions recited in the claims.
Regarding the claimed chimeric receptors comprising a broadly claimed genus of intracellular domains with a partial structure at best and the function of "two or more human or humanized transcriptional regulators" (claims 1, 2, 7, 12, 17, 21-23, 34, 36-38, 58, and 61), the instant specification discloses fusions of specific DNA binding domains structures fused to specific transactivation domain structures to generate transcriptional regulators that bind to specific DNA elements and either increase or decrease downstream transcription and protein expression (¶[0008]-[0009]). The instant specification discloses 6 different structures with the function of “DNA binding domain” (SEQ ID NO: 6-12), five of which are specific zinc-finger structures and one PAX6 DNA binding domain structure. The instant specification further discloses 19 specific transactivating domain structures (SEQ ID NO: 15-22 and 24-34) that can be fused to the DNA binding domains to generate functional transcriptional regulators. This limited group of structures do not sufficiently represent the broadly claimed genera of TM domains with a partial structure at best and the function “two or more transcriptional regulators”.
Moreover, there is insufficient written description of the required kind of structure-identifying information about the corresponding makeup of the claimed chimeric receptors constructs to demonstrate possession. Also, see Amgen Inc. v. Sanofi, Aventisub LLC, No. 2017-1480 (Fed. Cir. 2017). The Court reiterated that adequate written description must “contain enough information about the actual makeup of the claimed products . . . .” The Court simultaneously suggested that the “newly characterized antigen” test “flouts” section 112 because it “allows patentees to claim antibodies by describing something that is not the invention, i.e., the antigen.” The Court concluded that for written description of an antibody to be adequate when presented with “functional” terminology, there must be an established correlation in the art between structure and function.
Given the broadly claimed class of chimeric receptors, 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.
Regarding the claimed chimeric receptors comprising a broadly claimed genus of extracellular ligand binding domains with a partial structure at best and the functions of “binding affinity for a ligand” or “binds to CD19” (claims 1, 2, 7, 12, 17, 21-23, 34, 36-38, 58, and 61), the specification discloses only two examples of such ligand binding domains, two scFv structures, one that binds to CD19 and one that binds to ALPPL2. It is unlikely that antibodies or fragments thereof as defined by the claims which may contain less than the full complement of CDRs from the VH and VL of each of these scFv structures, fused to framework sequences have the required binding function. The specification provides no direction or guidance regarding how to produce antigen binding constructs with the functions of “binding affinity for a ligand” or “binds to CD19” as broadly defined by the claims.
Regarding the claimed chimeric receptors comprising a broadly claimed genus of linkers and the function of “capable of promoting oligomer formation of the chimeric polypeptide via intermolecular disulfide bonding” (claims 1, 2, 7, 12, 17, 21-23, 34, 36-38, 58, and 61), the instant specification provides no guidance on how to generate other linking polypeptide structures with this recited function. The only guidance the instant specification provides is to list the truncated CD8α hinge domain with this function.
Regarding the claimed chimeric receptors comprising a broadly claimed genus TM domains with a partial structure at best and the functions of “ligand-inducible proteolytic cleavage sites” and “extracellular ligand-binding domain induces cleavage at the one or more ligand-inducible proteolytic cleavage sites between the transcriptional regulator and the linking polypeptide” (claims 1, 2, 7, 12, 17, 21-23, 34, 36-38, 58, and 61), the instant specification only discloses examples of TM domain with ligand-inducible proteolytic cleavage sties, and provides not relationship between a polypeptide’s structure, defined by its amino acid sequence, and the functions of “ligand-inducible proteolytic cleavage sites” and “extracellular ligand-binding domain induces cleavage at the one or more ligand-inducible proteolytic cleavage sites between the transcriptional regulator and the linking polypeptide”. The only guidance the instant specification provides is to list individual structures with these functions, all of which are a specific Notch1 TM domain structure fused to a limited number of Notch SRS and RAMM domains (i.e., the TM domain of SEQ ID NO: 4, fused to SEQ ID NO: 5 and 75-79 and SEQ ID NO: 80-90, respectively). The specification provides no direction or guidance regarding how to produce additional TM domains with the functions of antigen binding constructs with the functions of “ligand-inducible proteolytic cleavage sites” and “extracellular ligand-binding domain induces cleavage at the one or more ligand-inducible proteolytic cleavage sites between the transcriptional regulator and the linking polypeptide” as broadly defined by the claims.
Regarding the claimed chimeric receptors comprising a broadly claimed genus of intracellular domains with a partial structure at best and the function of "two or more human or humanized transcriptional regulators" (claims 1, 2, 7, 12, 17, 21-23, 34, 36-38, 58, and 61), the instant specification provides no relationship between a polypeptide’s structure and the function of “transcriptional regulator”. The instant specification discloses specific species of transcriptional regulators which are fusions of DNA binding domains, such as ZF3, ZF6, ZF10, and PAX6 (SEQ ID NO: 6-12) and specific species of transactivation domains such as p65, GR Tau1, p53, ATF6, HSF1, HIF1, and Elf3 (SEQ ID NO: 15-22, 24-34, and 94-98).
Additionally, the prior art teaches that there is an unpredictability between a peptide’s amino acid sequence and binding affinity to a DNA strand. For example, Elrod-Erickson et al. (J Biol Chem. 1999 Jul 2;274(27):19281-5. doi: 10.1074/jbc.274.27.19281) teaches that alterations to the amino acid sequence of a zinc-finger (ZF) DNA binding peptide has unpredictable effects on binding affinity. For example, substitutions of different amino acid residues that are known to contact DNA to alanine were found to either decrease (R18A) or increase (D20A) DNA binding affinity, when all of the amino acid substitutions were predicted to reducing DNA binding affinity (see Table 1), demonstrating a unpredictable effect between a polypeptide’s structure, dictated by its amino acid sequence, and DNA binding affinity to generate functional polypeptides with the function of "two or more human or humanized transcriptional regulators".
Furthermore, Lin et al. (Genes Dev. 1994 May 15;8(10):1235-46. doi: 10.1101/gad.8.10.1235. PMID: 7926727) teaches that amino acid substitutions in transactivation peptides have different effects on transcriptional regulation, as single amino acid substitutions in the TAD of p53 can change transcriptional activity varying degrees (Table 1), with some mutations increasing transcriptional activity (Pos 15 Ser to Gly), while other can reduce activity by 92% (Pos 273 Arg to His), further demonstrating a unpredictable effect between a polypeptide’s structure, dictated by its amino acid sequence, and transcriptional activation activity to generate functional polypeptides with the function of "two or more human or humanized transcriptional regulators".
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 chimeric receptors falling within the scope of the genus or of a recitation of structural features common to members of the genus, which features constitute a substantial portion of the genus. See Eli Lilly, 119F.3d at 1568, 43 USPQ2d at 1406.
Claims 1, 2, 7, 12, 17, 21-23, 34, 36-38, 58, and 61 do not meet the requirements of 35 U.S.C. 112(a) for written description.
Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, makes clear that "applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the written description inquiry, whatever is now claimed." (See page 1117.) The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed." (See Vas-Cath at page 1116.). Consequently, Applicant was not in possession of the instant claimed invention. See University of California v. Eli Lilly and Co. 43 USPQ2d 1398.
Applicant is invited to point to clear support or specific examples of the claimed invention in the specification as-filed.
To overcome this rejection, it is recommended to amend claim 1 to recite specific chimeric receptor structures, defined by their amino acid sequences, with all of the functions recited in the claim.
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 12, 27, 36, and 37 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 12 contains the trademark/trade name Nanobody®. 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 a single domain antibody and, accordingly, the identification/description is indefinite.
Additionally, claim 12 is indefinite because it is currently unclear how diabodies, triabodies, minibodies, F(ab’)2 fragment, or a F(ab)v, all of which are dimeric polypeptides, can be incorporated into the single polypeptide chain in claim 1.
The recitation "derived from" in claims 27, 36, and 37 are indefinite because it is unclear what changes or how many changes could have occurred to result in a derivative. Derivation only describes the source and not the result. Please remove the “derived from” claim language to overcome this issue.
Additionally, claim 36 is indefinite because the claim recites “…ZF3, ZF4, ZF6, ZF10, and ZF11”. It is currently unclear what protein/peptide/domain(s) these are referring to. For example, it is currently unclear if ZF6 is the zinc-finger protein 6 from humans or Arabidopsis plants.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 2, 7, 12, 17, 21-23, 34, 36, 37, 58, and 61 are rejected under 35 U.S.C. 103 as being unpatentable over Lim et al. (U.S. PGPub 20180355011) in view of Alabanza et al. (Mol Ther. 2017 Nov 1;25(11):2452-2465. doi: 10.1016/j.ymthe.2017.07.013. Epub 2017 Jul 27), as evidenced by Chen et al. (J Magn Reson. 2022 Jul;340:107234. doi: 10.1016/j.jmr.2022.107234).
Instant claim 1 recites a chimeric receptor comprising, from N to C terminus, an extracellular ligand-binding domain, a linking polypeptide capable of oligomizeration via disulfide bonds, a TM domain comprising one or more ligand-inducible proteolytic cleavage sites, and an intracellular domain comprising two or more human/humanized transcriptional regulators.
Lim et al. teaches chimeric Notch receptors (Abstract), including, from N to C terminus a ligand binding domain, a notch domain comprising a TM domain with a S3 gamma secretase cleavage domain, a RAM domain, and an intracellular domain comprising a transcriptional activation domain (Fig. 1):
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Lim et al. further teaches that the intracellular signaling domain can comprise human/humanized transcription factors such as ATF6 (¶[0350]): “…in some cases, the intracellular domain is a transcriptional regulator…transcriptional regulators include…ATF6…GATA3…”
Lim et al. teaches that for a synNotch upon ligand binding, the notch core self-cleaves to release the intracellular domain (i.e., “binding of the ligand to the extracellular ligand-binding domain induces cleavage at the one or more ligand-inducible proteolytic cleavage sites”; Lim et al. Fig. 7)
Lim et al. additionally teaches the notch core that leads to intracellular domain cleavage can comprise the HD-C domain and TMD of notch (Fig. 4G):
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Lim et al. does not teach the CAR synNotch comprising a linking polypeptide capable of promoting oligomer formation of the chimeric polypeptide via intermolecular disulfide bonding (i.e., the limitations of instant claim 1).
Alabanza et al., in the same field of endeavor, teaches anti-CD19 extracellular domains that are suitable for use in chimeric receptors such as chimeric antigen receptors (Abstract). Alabanza et al. teaches that the extracellular domains comprise an anti-CD19 scFv fused to a CD8α hinge, fused to a TM domain an intracellular domain (Fig. 1A):
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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 Lim et al. in view of Alabanza et al. to generate a CAR synNotch receptor comprising an anti-CD19 scFv and CD8α hinge fused to the Notch core/TM and intracellular domains with a reasonable expectation of success, as Alabanza et al. teaches a functional extracellular ligand binding domain that can be used in the synNotch receptors of Lim et al. One would have been motivated to make this change for the purposes of generating a function anti-CD19 synNotch receptor.
Additionally, one would have been motivated to use the guidance of Lim et al. to try different notch cores and transcriptional regulators in the synNotch receptors, such as the Notch core with the HD-C and TM domains, as well as the transcriptional regulators ATF6 and GATA3 to optimize the synNotch receptors to generate receptors that have greater functionality to activate downstream transcription of genes in response to ligand binding.
The chimeric receptor generated by the combined teachings of Lim et al. in view of Alabanza et al. would generate a chimeric receptor comprising, from N to C terminus: an anti-CD19 scFv, a CD8α hinge, a HD-C/TM notch core with the S3 gamma secretase cleavage site, and an intracellular domain comprising transcriptional regulators from ATF6 and GATA3. Note that this receptor does not contain the notch LNR domain.
Regarding the claimed functional limitations of linking polypeptides “capable of promoting oligomer formation of the chimeric polypeptide via intermolecular disulfide bonding”, Chen et al. is provided as an evidentiary reference to demonstrate that this function is inherent to the CD8α hinge domain. Chen et al. teaches (Section 3.3): “…the CD8α H can form intermolecular disulfide bonds when its cysteines are not reduced…”. Therefore, the combined references of Lim et al. in view of Alabanza et al., as evidenced by Chen et al. teaches the limitations of instant claim 1.
Regarding claim 2, Alabanza et al. teaches that CD19 is expressed on human CLL cells (pg. 2454): “…CD19+ primary human chronic lymphocytic leukemia (CLL) cells were used…”, meeting the claim limitations.
Regarding claims 7 and 12, Alabanza et al. teaches that the anti-CD19 targeting agent is an anti-CD19 scFv (supra), meeting the claimed limitations.
Regarding claim 17, Alabanza et al. teaches the CD8α hinge (supra), meeting the claim limitations.
Regarding claim 21, Lim et al. teaches that the notch TM domain comprises a S3 gamma secretase site (Fig. 1 supra), meeting the claim limitations.
Regarding claim 22, Lim et al. teaches that he notch TM domain can comprise SEQ ID NO: 7, which is 89.6% identical to instant SEQ ID NO: 4, meeting the claim limitations:
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Regarding claim 23, Lim et al. teaches the notch TM domain can further comprise the RKRRR stop-transfer sequence (SEQ ID NO: 4), which is the STS of instant SEQ ID NO 75, meeting the claim limitations.
Regarding claims 34 and 37, Lim et al. teaches that the synNotch ICD can comprise the transcriptional activators ATF6 and GATA3 (supra), meeting the claim limitations.
Regarding claim 36, Lim et al. teaches that the synNotch ICD can also comprise a DNA binding domain, such as ZFHD1 (Fig. 37B), meeting the claim limitations.
Regarding claim 58, Lim et al. teaches that the synNotch can be put into a kit (i.e., “a composition”) comprising the receptor and a buffer (i.e., “a pharmaceutically acceptable carrier”), including dilutions buffers (¶[0610]-[0613]), meeting the claim limitations.
Regarding claim 61, Lim et al. teaches the synNotch modulates cell activity (¶[0602]), 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.
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, 7, 12, 21-23, 34, 36, 37, 58, 61 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No. 11,897,932 (Pat ‘932) in view of over Lim et al. (U.S. PGPub 20180355011, supra).
Pat ‘932 claims a chimeric polypeptide comprising, from N to C terminus, an extracellular ligand binding domain comprising an scFv, a linking domain comprising SEQ ID NO: 19, a TM domain with one or more proteolytic cleavage sites, and an intracellular domain comprising a transcriptional regulator, wherein binding of the ligand to the extracellular domain induces cleavage at the proteolytic site, wherein the polypeptide does not comprise a LNR or HD domain (claim 1).
Pat ‘932 does not claim the intracellular domain comprising two or more human/humanized transcriptional regulators (i.e., the limitations of instant claim 1).
Lim et al., in the same field of endeavor, teaches chimeric Notch receptors (Abstract), including, from N to C terminus a ligand binding domain, a notch domain comprising a TM domain with a S3 gamma secretase cleavage domain, a RAM domain, and an intracellular domain comprising a transcriptional activation domain (Fig. 1). Lim et al. further teaches that the intracellular signaling domain can comprise human/humanized transcription factors such as ATF6 (¶[0350]): “…in some cases, the intracellular domain is a transcriptional regulator…transcriptional regulators include…ATF6…GATA3…”
It would have been obvious to one with ordinary skill in the art to have modified the invention claimed by Pat ‘932 in view of Lim et al. tried the human/humanized transcriptional regulators such as ATF6 and GATA3 (i.e., the limitations of instant claims 1, 34, and 37) with a reasonable expectation of success, as Lim et al. teaches these are suitable regulators that can be incorporated into a chimeric synNotch such as the ones claimed by Pat ‘932. One would have been motivated to make this change for the purposes of optimizing a chimeric synNotch to improve its effects, such as activating cells.
Regarding instant claim 2, Pat ‘932 claims the target is from a human cell (claim 4), meeting the claim limitations.
Regarding instant claims 7 and 12, Pat ‘932 claims the extracellular binding domain is an scFv that binds to CD19 (claims 1 and 7), meeting the claim limitations.
Regarding instant claim 21, Pat ‘932 claims the TM domain comprising a gamma secretase site (claim 10), meeting the claim limitations.
Regarding instant claim 22, Lim et al. teaches that he notch TM domain can comprise SEQ ID NO: 7, which is 89.6% identical to instant SEQ ID NO: 4 (see supra), meeting the claim limitations.
Regarding instant claim 23, Pat ‘932 claims the TM comprising a stop transfer sequence (claim 2), meeting the claim limitations.
Regarding claim 36, Lim et al. teaches that the synNotch ICD can also comprise a DNA binding domain, such as ZFHD1 (Fig. 37B), meeting the claim limitations.
Regarding claim 58, Lim et al. teaches that the synNotch can be put into a kit (i.e., “a composition”) comprising the receptor and a buffer (i.e., “a pharmaceutically acceptable carrier”), including dilutions buffers (¶[0610]-[0613]), meeting the claim limitations.
Regarding claim 61, Lim et al. teaches the synNotch modulates cell activity (¶[0602]), meeting the claim limitations.
Therefore, the invention as a whole was prima facie obvious variant of the invention claimed by at ‘932 in view of Lim et al., especially in the absence of evidence to the contrary.
Claims 1, 2, 7, 12, 17, 21-23, 34, 36, 37, 58, 61 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-30 of U.S. Patent No. 11,202,801 (Pat ‘801) in view of over Lim et al. (supra).
Pat ‘801 claims a chimeric polypeptide comprising, from N to C terminus, an extracellular ligand binding domain, a linking domain comprising a CD8α hinge domain (i.e., the limitations of instant claim 17), a TM domain with one or more proteolytic cleavage sites, and an intracellular domain comprising a transcriptional regulator, wherein binding of the ligand to the extracellular domain induces cleavage at the proteolytic site, wherein the polypeptide does not comprise a LNR or HD domain (claim 1).
Pat ‘801 additionally claims the target being on a human cell (claim 4), the target is CD19 and the extracellular binding domain comprises and scFv (claims 7, 9, and 10), which are the limitations of instant claims 2, 7, and 12.
Pat ‘801 further claims the TM domain comprising a gamma secretase site (claim 11) and a stop transfer sequence (claim 2), which are the limitations of instant claims 21 and 23.
Pat ‘801 does not claim the intracellular domain comprising two or more human/humanized transcriptional regulators (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 Pat ‘801 in view of Lim et al. for the same reasons discussed for Pat ‘932 supra.
Claims 1, 2, 7, 12, 17, 21-23, 34, 36, 37, 58, 61 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-29 of U.S. Patent No. 11,617,766 (Pat ‘766) in view of over Lim et al. (supra).
Pat ‘766 claims a chimeric polypeptide comprising, from N to C terminus, an extracellular ligand binding domain, a linking domain comprising a CD8α hinge domain (i.e., the limitations of instant claim 17), a TM domain with one or more proteolytic cleavage sites, and an intracellular domain comprising a transcriptional regulator, wherein binding of the ligand to the extracellular domain induces cleavage at the proteolytic site, wherein the polypeptide does not comprise a LNR or HD domain (claim 1).
Pat ‘766 additionally claims the target being on a human cell (claim 4), the target is CD19 and the extracellular binding domain comprises and scFv (claims 7, 9, and 10), which are the limitations of instant claims 2, 7, and 12.
Pat ‘766 further claims the TM domain comprising a gamma secretase site (claim 11) and a stop transfer sequence (claim 2), which are the limitations of instant claims 21 and 23.
Pat ‘766 does not claim the intracellular domain comprising two or more human/humanized transcriptional regulators (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 Pat ‘766 in view of Lim et al. for the same reasons discussed for Pat ‘932 supra.
Claims 1, 2, 7, 12, 17, 21-23, 34, 36, 37, 58, 61 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 6, 10-15, 17, 18, 20, 23-27, 31, 35-37, 41, 51, 52, 55, 62, 65, 74, 75 of copending Application No. 17/763,110 (App ‘110) in view of over Lim et al. (supra).
App ‘110 claims a chimeric polypeptide comprising, from N to C terminus, an extracellular ligand binding domain, a linking domain comprising a hinge domain (i.e., the limitations of instant claim 17), a TM domain with one or more proteolytic cleavage sites, and an intracellular domain comprising a transcriptional regulator, wherein binding of the ligand to the extracellular domain induces cleavage at the proteolytic site, wherein the polypeptide does not comprise a LNR or HD domain (claim 1).
App ‘110 additionally claims the target being on a human cell such as CD19 and the extracellular binding domain comprises and scFv (claims 14 and 18), which are the limitations of instant claims 2, 7, and 12.
App ‘110 further claims the TM domain comprising a gamma secretase site (claim 23) and a stop transfer sequence (claim 2), which are the limitations of instant claims 21 and 23.
App ‘110 does not claim the intracellular domain comprising two or more human/humanized transcriptional regulators (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 ‘110 in view of Lim et al. for the same reasons discussed for Pat ‘932 supra. This is a provisional double patenting rejection.
Claims 1, 2, 7, 12, 17, 21-23, 34, 36, 37, 58, 61 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, 6-11, 13, 14, 16, 19-21, 24, 28, 32, 33, 37, 47, 48, 51, 58, 61, 70, 71 of copending Application No. 17/763,116 (App ‘116) in view of over Lim et al. (supra).
App ‘116 claims a chimeric polypeptide comprising, from N to C terminus, an extracellular ligand binding domain, a linking domain comprising a hinge domain (i.e., the limitations of instant claim 17), a TM domain with one or more proteolytic cleavage sites, and an intracellular domain comprising a transcriptional regulator, wherein binding of the ligand to the extracellular domain induces cleavage at the proteolytic site, wherein the polypeptide does not comprise a LNR or HD domain (claim 1).
App ‘116 additionally claims the target being on a human cell such as CD19 and the extracellular binding domain comprises and scFv (claims 10 and 14), which are the limitations of instant claims 2, 7, and 12.
App ‘116 further claims the TM domain comprising a gamma secretase site (claim 3) and a stop transfer sequence (claim 1(d)(ii)), which are the limitations of instant claims 21 and 23.
App ‘116 does not claim the intracellular domain comprising two or more human/humanized transcriptional regulators (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 ‘116 in view of Lim et al. for the same reasons discussed for Pat ‘932 supra. This is a provisional double patenting rejection.
Claims 1, 2, 7, 12, 21-23, 34, 36, 37, 58, 61 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 17-23, 25, 26, 28, 31-36, 40, 41, 43, 52, 62, 63, 66, 69, 71, 81-83 of copending Application No. 17/763,122 (App ‘122) in view of over Lim et al. (supra).
App ‘122 claims a chimeric polypeptide comprising, from N to C terminus, an extracellular ligand binding domain, a linking domain, a TM domain with one or more proteolytic cleavage sites, and an intracellular domain comprising a transcriptional regulator, wherein binding of the ligand to the extracellular domain induces cleavage at the proteolytic site, wherein the polypeptide does not comprise a LNR or HD domain (claim 1).
App ‘122 additionally claims the target being on a human cell such as CD19 and the extracellular binding domain comprises and scFv (claims 22 and 26), which are the limitations of instant claims 2, 7, and 12.
App ‘122 further claims the TM domain comprising a gamma secretase site (claim 31) and a stop transfer sequence (claim 2), which are the limitations of instant claims 21 and 23.
App ‘122 does not claim the intracellular domain comprising two or more human/humanized transcriptional regulators (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 ‘122 in view of Lim et al. for the same reasons discussed for Pat ‘932 supra. This is a provisional double patenting rejection.
Claims 1, 2, 7, 12, 21-23, 34, 36, 37, 58, 61 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, 4, 6, 8-10, 12, 13, 18-20, 24, 25, 31-36, 40, 51, 52, 55, 62, 66, 75, 76 of copending Application No. 17/762,685 (App ‘685) in view of over Lim et al. (supra).
App ‘685 claims a chimeric polypeptide comprising, from N to C terminus, an extracellular ligand binding domain, a linking domain, a TM domain with one or more proteolytic cleavage sites, and an intracellular domain comprising a transcriptional regulator, wherein binding of the ligand to the extracellular domain induces cleavage at the proteolytic site, wherein the polypeptide does not comprise a LNR or HD domain (claim 1).
App ‘685 additionally claims the target being on a human cell such as CD19 and the extracellular binding domain comprises and scFv (claims 4, 9, 13), which are the limitations of instant claims 2, 7, and 12.
App ‘685 further claims the TM domain comprising a gamma secretase site (claim 18) and a stop transfer sequence (claim 1(c)), which are the limitations of instant claims 21 and 23.
App ‘685 does not claim the intracellular domain comprising two or more human/humanized transcriptional regulators (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 ‘685 in view of Lim et al. for the same reasons discussed for Pat ‘932 supra. This is a provisional double patenting rejection.
Claims 1, 2, 7, 12, 21-23, 34, 36, 37, 58, 61 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-45, 49, 53, 59, 60, 63, 70, 73, 82, 83, 86, and 89 of copending Application No. 17/762,687 (App ‘687) in view of over Lim et al. (supra).
App ‘687 claims a chimeric polypeptide comprising, from N to C terminus, an extracellular ligand binding domain, a linking domain, a TM domain with one or more proteolytic cleavage sites, and an intracellular domain comprising a transcriptional regulator, wherein binding of the ligand to the extracellular domain induces cleavage at the proteolytic site, wherein the polypeptide does not comprise a LNR or HD domain (claims 1 and 2).
App ‘687 additionally claims the target being on a human cell such as CD19 and the extracellular binding domain comprises and scFv (claims 21 and 25-27), which are the limitations of instant claims 2, 7, and 12.
App ‘687 further claims the TM domain comprising a gamma secretase site (claim 30) and a stop transfer sequence (claim 3), which are the limitations of instant claims 21 and 23.
App ‘685 does not claim the intracellular domain comprising two or more human/humanized transcriptional regulators (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 ‘687 in view of Lim et al. for the same reasons discussed for Pat ‘932 supra. This is a provisional double patenting rejection.
Claims 1, 2, 7, 12, 17, 21-23, 34, 36, 37, 58, 61 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 3, 8, 12, 13, 18, 34, 40, 41, 46, 49, 54, 68, 92, 95, and 100-104 of copending Application No. 17/995,751 (App ‘751) in view of over Lim et al. (supra).
App ‘751 claims a chimeric polypeptide comprising, from N to C terminus, an extracellular ligand binding domain, a linking domain comprising a hinge domain (i.e., the limitations of instant claim 17), a TM domain with one or more proteolytic cleavage sites, and an intracellular domain comprising a transcriptional regulator, wherein binding of the ligand to the extracellular domain induces cleavage at the proteolytic site, wherein the polypeptide does not comprise a LNR or HD domain (claim 1).
App ‘751 additionally claims the target being on a human cell such as CD19 and the extracellular binding domain comprises and scFv (claims 3 and 13), which are the limitations of instant claims 2, 7, and 12.
App ‘751 further claims the TM domain comprising a gamma secretase site (claim 18) and a stop transfer sequence (claim 2), which are the limitations of instant claims 21 and 23.
App ‘751 does not claim the intracellular domain comprising two or more human/humanized transcriptional regulators (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 ‘751 in view of Lim et al. for the same reasons discussed for Pat ‘932 supra. This is a provisional double patenting rejection.
Claims 1, 2, 7, 12, 21-23, 34, 36, 37, 58, 61 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 17-23, 25, 26, 28, 31-36, 40, 41, 43, 52, 62, 63, 66, 69, 73, 81-83, and 85-87 of copending Application No. 17/995,765 (App ‘765) in view of over Lim et al. (supra).
App ‘765 claims a chimeric polypeptide comprising, from N to C terminus, an extracellular ligand binding domain, a linking domain, a TM domain with one or more proteolytic cleavage sites, and an intracellular domain comprising a transcriptional regulator, wherein binding of the ligand to the extracellular domain induces cleavage at the proteolytic site, wherein the polypeptide does not comprise a LNR or HD domain (claim 1).
App ‘765 additionally claims the target being on a human cell such as CD19 and the extracellular binding domain comprises and scFv (claims 22, 26), which are the limitations of instant claims 2, 7, and 12.
App ‘765 further claims the TM domain comprising a gamma secretase site (claim 31) and a stop transfer sequence (claim 2), which are the limitations of instant claims 21 and 23.
App ‘765 does not claim the intracellular domain comprising two or more human/humanized transcriptional regulators (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 ‘765 in view of Lim et al. for the same reasons discussed for Pat ‘932 supra. This is a provisional double patenting rejection.
Claims 1, 2, 7, 12, 21-23, 34, 36, 37, 58, 61 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 31-55 of copending Application No. 18/178,440 (App ‘440) in view of over Lim et al. (supra).
App ‘440 claims a chimeric polypeptide comprising, from N to C terminus, an extracellular ligand binding domain, a linking domain, a TM domain with one or more proteolytic cleavage sites, and an intracellular domain comprising a transcriptional regulator, wherein binding of the ligand to the extracellular domain induces cleavage at the proteolytic site, wherein the polypeptide does not comprise a LNR or HD domain (claim 31).
App ‘440 additionally claims the target being on a human cell such as CD19 and the extracellular binding domain comprises and scFv (claims 34, 36, and 38), which are the limitations of instant claims 2, 7, and 12.
App ‘440 further claims the TM domain comprising a gamma secretase site (claim 41) and a stop transfer sequence (claim 32), which are the limitations of instant claims 21 and 23.
App ‘440 does not claim the intracellular domain comprising two or more human/humanized transcriptional regulators (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 ‘440 in view of Lim et al. for the same reasons discussed for Pat ‘932 supra. This is a provisional double patenting rejection.
Claims 1, 2, 7, 12, 21-23, 34, 36, 37, 58, 61 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 21-28, 30, 31, 33, 35, 39-46 of copending Application No. 18/393,538 (App ‘538) in view of over Lim et al. (supra).
App ‘538 claims a chimeric polypeptide comprising, from N to C terminus, an extracellular ligand binding domain, a linking domain, a TM domain with one or more proteolytic cleavage sites, and an intracellular domain comprising a transcriptional regulator, wherein binding of the ligand to the extracellular domain induces cleavage at the proteolytic site, wherein the polypeptide does not comprise a LNR or HD domain (claim 21).
App ‘538 additionally claims the target being on a human cell such as CD19 and the extracellular binding domain comprises and scFv (claims 21 and 39), which are the limitations of instant claims 2, 7, and 12.
App ‘538 further claims the TM domain comprising a gamma secretase site (claim 40) and a stop transfer sequence (claim 31), which are the limitations of instant claims 21 and 23.
App ‘538 does not claim the intracellular domain comprising two or more human/humanized transcriptional regulators (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 ‘538 in view of Lim et al. for the same reasons discussed for Pat ‘932 supra. This is a provisional double patenting rejection.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALEC JON PETERS whose telephone number is (703)756-5794. The examiner can normally be reached Monday-Friday 8:30am - 6:00pm EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Misook Yu can be reached at (571) 272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ALEC JON PETERS/Examiner, Art Unit 1641
/MISOOK YU/Supervisory Patent Examiner, Art Unit 1641
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