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/Restrictions
Applicant’s election without traverse of the below-listed species in the reply filed on 11/26/2025 is acknowledged.
Elected Species:
VH CDRs 1-3 and VL CDRs 1-3 corresponding to SEQ ID NOs: 17, 18, 19, 22, 23, and 24, respectively;
VH and VL corresponding to SEQ ID NOs: 16 and 21, respectively;
Costimulatory domain of CD28 corresponding to SEQ ID NO: 8;
Transmembrane domain of CD28 corresponding to SEQ ID NO: 6;
Full-length CAR amino acid sequence corresponding to SEQ ID NO: 32; and
Full-length CAR polynucleotide sequence corresponding to SEQ ID NO: 31.
Claim Status
Claims 1-80 have been cancelled as requested in the amendment filed on 11/26/2025. Following the amendment, claims 81-100 are pending in the instant application.
Claims 81-100 are under examination in the instant 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.
Claims 81-100 have an effective filing date of April 01, 2016 corresponding to PRO 62/317,068.
Drawings
The drawings are objected to because Figures 4-6 comprise text that is blurry and very difficult to read. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Specification
Applicant is reminded of the proper content of an abstract of the disclosure.
A patent abstract is a concise statement of the technical disclosure of the patent and should include that which is new in the art to which the invention pertains. The abstract should not refer to purported merits or speculative applications of the invention and should not compare the invention with the prior art.
If the patent is of a basic nature, the entire technical disclosure may be new in the art, and the abstract should be directed to the entire disclosure. If the patent is in the nature of an improvement in an old apparatus, process, product, or composition, the abstract should include the technical disclosure of the improvement. The abstract should also mention by way of example any preferred modifications or alternatives.
Where applicable, the abstract should include the following: (1) if a machine or apparatus, its organization and operation; (2) if an article, its method of making; (3) if a chemical compound, its identity and use; (4) if a mixture, its ingredients; (5) if a process, the steps.
Extensive mechanical and design details of an apparatus should not be included in the abstract. The abstract should be in narrative form and generally limited to a single paragraph within the range of 50 to 150 words in length.
See MPEP § 608.01(b) for guidelines for the preparation of patent abstracts.
The abstract of the disclosure is objected to because it is less than 50 words in length. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
The disclosure is further objected to because it contains an embedded hyperlink and/or other form of browser-executable code at Page 2. 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://, www., or other browser-executable code. See MPEP § 608.01.
Claim Objections
Claims 82-83, 86-87, and 89-91 are objected to because of the following informalities: how sequences are listed is inconsistent with independent claim 81. The independent claim refers to sequences as "SEQ ID NO: 17", for example, and in claims 82-83, 86-87, and 89-91 the references to sequences are inconsistent and include "SEQ ID NO:16", for example, wherein there is no space between the colon and the sequence number. Applicant should amend the claims such that all references to sequences are consistently represented. Appropriate correction is required.
Claim 93 is objected to because of the following informalities: the claim currently recites "wherein the polynucleotide comprises a nucleic sequence", but should read "wherein the polynucleotide comprises a nucleic acid sequence". Appropriate correction is required.
Claim Interpretation
With regard to the sequence language recited in the instant claims, the following is noted:
According to broadest reasonable interpretation (BRI), the recitation of “comprises the amino acid sequence of SEQ ID NO…” is considered closed sequence language, wherein the claim requires the full-length of the recited sequence. This interpretation is applicable to claims 81-83, 86-87, and 89-91.
According to BRI, the recitation of “comprises an amino acid sequence selected from…” is considered open sequence language, wherein a sequence satisfying the above limitation includes any amino acid sequence comprising at least two consecutive amino acids from the recited group of sequences. This interpretation is applicable to claim 92.
According to BRI, the recitation of “comprises a nucleic [acid] sequence selected from…” is considered open sequence language, wherein a sequence satisfying the above limitation includes any nucleic acid sequence comprising at least two consecutive nucleotides from the recited group of sequences. This interpretation is applicable to claim 93.
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 81-100 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a WRITTEN DESCRIPTION rejection.
The claims are drawn to a method of preparing an immune cell, generally comprising introducing to the immune cell a polynucleotide encoding a chimeric antigen receptor (CAR) that binds to C-type lectin-like-1 (CLL-1) wherein the CAR comprises an scFv that binds CLL-1, a transmembrane domain, an intracellular activating domain that is a signaling domain of CD3 zeta, and wherein the scFv comprises heavy chain variable region (VH) and light chain variable region (VL) complementarity determining regions (VH CDRs 1-3 and VL CDRs 1-3, respectively) wherein:
the VH CDR1 comprises the amino acid sequence of SEQ ID NO: 17 or a variant derived therefrom with an amino acid substitution,
the VH CDR2 comprises the amino acid sequence of SEQ ID NO: 18 or a variant derived therefrom with an amino acid substitution,
the VH CDR3 comprises the amino acid sequence of SEQ ID NO: 19 or a variant derived therefrom with an amino acid substitution,
the VL CDR1 comprises the amino acid sequence of SEQ ID NO: 22 or a variant derived therefrom with an amino acid substitution,
the VL CDR2 comprises the amino acid sequence of SEQ ID NO: 23 or a variant derived therefrom with an amino acid substitution, and
the VL CDR3 comprises the amino acid sequence of SEQ ID NO: 24 or a variant derived therefrom with an amino acid substitution.
Thus, the claims identify the scFv of the CAR by the function of binding CLL-1, and a partial sequence structure that comprises a VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 corresponding to full-length SEQ ID NOs: 17, 18, 19, 22, 23, and 24, respectively, or variants derived therefrom with an amino acid substitution. Thus, the claims encompass a vast genus of possible scFv variants comprising variable VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and/or VL CDR3 sequences and required to bind CLL-1.
Pages 28-29 of the instant specification discloses the consensus sequences corresponding to antigen binding molecules of the invention; each CDR has multiple, variable X residues. The instant specification discloses four structurally similar antigen binding molecules defined by their full-length VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 sequences, as disclosed on Pages 30-31; the four discloses species of antigen binding molecules (i.e., scFvs) correspond to secondary identifiers 24C1, 24C8, 20C5.1, and 20C5.2, and all corresponding sequences (VH and VL CDRs and full-length VH and VL sequences) are disclosed at Paragraphs 0271-0280, 0305-0314, 0328-0337, and 0350-0359, respectively.
Thus, the instant specification discloses making four structurally similar scFv and describes the complete VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 sequences and full-length VH and VL sequences corresponding to 24C1, 24C8, 20C5.1, and 20C5.2, that all function to bind CLL-1. The specification fails to disclose any other VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 sequence variants comprising amino acid substitutions that possess the function of binding to CLL-1.
To provide adequate written description and evidence of possession of the claimed antibody genus, the instant specification can structurally describe representative antibody variants that function to bind CLL-1, or describe structural features common to the members of the genus, which features constitute a substantial portion of the genus. Alternatively, the specification can show that the claimed invention is complete by disclosure of sufficiently detailed, relevant identifying characteristics, functional characteristics when coupled with a known or disclosed correlation between function and structure, or some combination of such characteristics (see University of California v. Eli Lilly and Co., 119 F.3d 1559, 43 USPQ2d 1398 (Fed. Cir. 1997) and Enzo Biochem, Inc. V. Gen-Probe Inc.).
In this case, the only factor present in the claims is a recitation of the antibody function, “binds to C-type lectin-like-1”, and partial sequence structure as stated above. The instant specification fails to describe structural features common to the members of the antibody genus, which features constitute a substantial portion of the genus because the instant specification fails to disclose representative scFv variant sequences that function as claimed. A definition by function does not suffice to define the genus because it is only an indication of what the antibody does, rather than what it is. Other than for the scFvs 24C1, 24C8, 20C5.1, and 20C5.2, the specification fails to provide the VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 structural features coupled to the claimed functional characteristics. The instant specification fails to describe a representative number of scFv sequence variants for the genus of scFvs that function as claimed. Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the claimed genus required to make the claimed antibodies.
The claims broadly encompass any possible combination of sequence variants comprising amino acid substitutions relative to recited full-length amino acids sequences for VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 that functions to bind CLL-1. Applicants have not established any reasonable structure-function correlation with regards to the residues in the CDRs that can be altered, and subsequently be combined, to yield and scFv comprising VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 sequences and still maintain CLL-1 binding function. Given the well-known high level of polymorphism of antibody CDR sequences and structure, the skilled artisan would not have been in possession of the vast repertoire of scFvs encompassed by the claimed invention. One could not reasonably or predictably extrapolate the structure of a variant scFv comprising amino acid substitutions relative to the recited VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 sequences required to bind CLL-1 as broadly claimed. Therefore, one could not readily envision members of the broadly claimed genus.
Although Applicants may argue that it is possible to screen for antibodies that bind CLL-1 and function as claimed, the court found in (Rochester v. Searle, 358 F.3d 916, Fed Cir., 2004) that screening assays are not sufficient to provide adequate written description for an invention because they are merely a wish or plan for obtaining the claimed chemical invention. “As we held in Lilly, “[a]n adequate written description of a DNA … ‘requires a precise definition, such as by structure, formula, chemical name, or physical properties,’ not a mere wish or plan for obtaining the claimed chemical invention.” 119 F.3d at 1566 (quoting Fiers, 984 F.2d at 1171). For reasons stated above, that requirement applies just as well to non-DNA (or RNA) chemical inventions.” Knowledge of screening methods provides no information about the structure of any future antibodies yet to be discovered that may function as claimed. The CLL-1 antigen provides no information about the structure of an antibody that binds to it.
Given the lack of representative examples to support the full scope of the claimed variant antibodies, and lack of reasonable structure-function correlation with regards to the unknown variable sequences in the CDRs, and their subsequent combinations, that provide CLL-1-binding function, the present claims lack adequate written description. Thus, the specification does not provide an adequate written description of scFv variants that bind CLL-1 and comprise amino acid substitutions relative to the recited VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 sequences that is required to practice the claimed invention.
Examiner Suggestion: Examiner suggests amending claim 81 to recite: A method for preparing an immune cell, the method comprising introducing to the immune cell a polynucleotide encoding a chimeric antigen receptor (CAR) that binds to C-type lectin-like-1 ("CLL-1"), wherein the CAR comprises a single chain Fv (scFv) that binds CLL-1, a transmembrane domain, and an intracellular activating domain that is a signaling domain of CD3 zeta, and wherein the scFv comprises a heavy chain variable region (VH) comprising VH complementarity determining regions ("CDRs") 1, VH CDR2, and VH CDR3, and a light chain variable region (VL) comprising VL CDR1, VL CDR2, and VL CDR3, wherein:
the VH CDR1 comprises the amino acid sequence of SEQ ID NO: 17
the VH CDR2 comprises the amino acid sequence of SEQ ID NO: 18
the VH CDR3 comprises the amino acid sequence of SEQ ID NO: 19
the VL CDR1 comprises the amino acid sequence of SEQ ID NO: 22
the VL CDR2 comprises the amino acid sequence of SEQ ID NO: 23
the VL CDR3 comprises the amino acid sequence of SEQ ID NO: 24 ;
the VH CDR1 comprises the amino acid sequence of SEQ ID NO: 51
the VH CDR2 comprises the amino acid sequence of SEQ ID NO: 52
the VH CDR3 comprises the amino acid sequence of SEQ ID NO: 53
the VL CDR1 comprises the amino acid sequence of SEQ ID NO: 56
the VL CDR2 comprises the amino acid sequence of SEQ ID NO: 57
the VL CDR3 comprises the amino acid sequence of SEQ ID NO: 58
the VH CDR1 comprises the amino acid sequence of SEQ ID NO: 73
the VH CDR2 comprises the amino acid sequence of SEQ ID NO: 74
the VH CDR3 comprises the amino acid sequence of SEQ ID NO: 75
the VL CDR1 comprises the amino acid sequence of SEQ ID NO: 78
the VL CDR2 comprises the amino acid sequence of SEQ ID NO: 79
the VL CDR3 comprises the amino acid sequence of SEQ ID NO: 80
the VH CDR1 comprises the amino acid sequence of SEQ ID NO: 95
the VH CDR2 comprises the amino acid sequence of SEQ ID NO: 96
the VH CDR3 comprises the amino acid sequence of SEQ ID NO: 97
the VL CDR1 comprises the amino acid sequence of SEQ ID NO: 100
the VL CDR2 comprises the amino acid sequence of SEQ ID NO: 101
the VL CDR3 comprises the amino acid sequence of SEQ ID NO: 102
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 81-100 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 and 21-28 of U.S. Patent No. 10,597,456 (herein after referred to as "reference patent") in view of US 2016/0051651 A1 (herein after referred to as "Brogdon").
Claims 1-19 and 21-28 of the reference patent are all drawn to CARs that bind CLL-1, wherein the CAR is a polypeptide that comprises a transmembrane domain, and an intracellular activating domain that is a signaling domain of CD3 zeta, wherein the scFv comprises a VH and VL pair. The claims disclose that the VH and VL pair may be selected from, for example: (1) a VH region comprising complementarity determining regions (“CDRs”) 1, 2, and 3 with amino acid sequences SEQ ID NO: 17, SEQ ID NO: 18, and SEQ ID NO: 19, respectively, and a VL region comprising CDRs 1, 2, and 3 with amino acid sequences SEQ ID NO: 22, SEQ ID NO: 23, and SEQ ID NO: 24, respectively; and/or (2) a VH region comprising the amino acid sequence of SEQ ID NO: 16 and a VL region comprising the amino acid sequence of SEQ ID NO: 21. It is noted that reference patent SEQ ID NOs: 17, 18, 19, 22, 23, 24, 16, and 21 are exact matches to instant SEQ ID NOs: 17, 18, 19, 22, 23, 24, 16, and 21, respectively. The patent claims further indicate: the signaling domain of CD3 zeta comprises the amino acid sequence set forth in SEQ ID NO: 10; the CAR may further comprise a costimulatory domain signaling region of CD28, which comprises SEQ ID NO: 8; the CAR comprises an extracellular and transmembrane domain of CD28 as set forth in SEQ ID NO: 2; the transmembrane domain is a CD28 transmembrane domain comprising SEQ ID NO: 6; and the linker of the scFv comprises at least one of SEQ ID NOs: 130 or 132. It is noted that reference patent SEQ ID NOs: 10, 8, 2, 6, 130, and 132 are exact matches to instant SEQ ID NOs: 10, 8, 2, 6, 130, and 132, respectively. Additionally, the patent claims provide a CAR polypeptide comprising an amino acid sequence as set forth in SEQ ID NO: 32 and an isolated polynucleotide comprising a nucleic acid sequence as set forth in SEQ ID NO: 31. It is noted that reference patent SEQ ID NOs: 32 and 31 are exact matches for instant SEQ ID NOs: 32 and 31, respectively. The patent claims further recite isolated polynucleotides encoding the CARs and vectors comprising the isolated polynucleotide, and immune cells comprising the vectors wherein: (1) said vectors may be retroviral vectors, DNA vectors, RNA vectors, plasmids, an adenoviral vector, an adenovirus associated vector, or a lentiviral vector; and (2) the immune cells may be a T cell, a tumor infiltrating lymphocyte (TIL), an NK cell, or an NK-T cell wherein said immune cells may more specifically be autologous T cells or allogenic T cells. As such, the reference patent claims the instantly claimed CARs, including the full-length amino acid and polynucleotide sequences thereof, vectors comprising said polynucleotide sequences, and immune cells comprising the vectors; the reference patent therefore reads on the CARs, polynucleotides, vectors, and immune cells of instant claims 81-98. However, it is noted that the reference patent does not explicitly claim a method for preparing an immune cell comprising, generally, introducing to the immune cell a polynucleotide encoding a CAR wherein, more specifically, said introducing is by transfection or transduction. This deficiency is remedied by Brogdon.
Brogdon discloses chimeric antigen receptors (CARs) specific to CLL-1, vectors encoding the same, and recombinant cells comprising the CLL-1 CAR (Abstract). The invention pertains to a method of making a cell comprising transducing a cell, e.g., an immune effector cell, e.g., a T cell or a NK cell, with a vector of comprising a nucleic acid encoding a CAR of the invention (Paragraph 0060); the vector is selected from the group consisting of a DNA, a RNA, a plasmid, a lentivirus vector, adenoviral vector, or a retrovirus vector (Paragraph 0055). More specifically, Brogdon discloses that ex vivo procedures are well known in the art; briefly, cells are isolated from a mammal (e.g., a human) and genetically modified (i.e., transduced
or transfected in vitro) with a vector expressing a CAR of the invention (Paragraph 0756). Additionally, Brogdon notes that the mammalian recipient (of a composition comprising the CAR/CAR-modified immune cells of the invention) may be a human and the CAR-modified
cell can be autologous with respect to the recipient or, alternatively, the cells can be allogeneic, syngeneic or xenogeneic with respect to the recipient (Id.). Thus, Brogdon discloses methods of preparing CAR-modified immune cells comprising contacting the immune cells with a polynucleotide encoding the CAR (i.e., a CLL-1 specific CAR) wherein the contacting is transduction or transfection in vitro and wherein it is further noted that the polynucleotide encoding the CAR may be provided in a vector, the immune cell may be a T cell or an NK cell, and the immune cells may be autologous or allogenic. Brogdon further discloses that the CARs and CAR-modified immune cells of the invention can be used in a method of treating cancer in a subject wherein the method comprises administering to the subject a CLL-1 CAR-expressing cell (e.g., CLL-1 CART or CLL-1 CAR-expressing NK cell) of the invention such that the cancer is treated in the subject; cancers to be treated include a cancer associated with expression of CLL-1, such as a hematological cancer wherein a hematologic cancer includes but is not limited to leukemia (such as acute myelogenous leukemia, chronic myelogenous leukemia, acute lymphoid leukemia, chronic lymphoid leukemia and myelodysplastic syndrome) and malignant lymphoproliferative conditions, including lymphoma (such as multiple myeloma, non-Hodgkin's lymphoma, Burkitt's lymphoma, and small cell- and large cell follicular lymphoma), minimal residual disease, MRD, e.g., of a leukemia, e.g., of AML or MDS (Paragraph 0750).
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to prepare the immune cell comprising CLL-1 CAR of the reference patent utilizing the method of Brogdon to arrive at a method for preparing an immune cell (e.g., an autologous or allogenic T cell) wherein the method comprises introducing to the immune cell a polynucleotide encoding the CLL-1 specific CAR wherein said introducing comprises, for example, in vitro transduction of said immune cell with said polynucleotide or a vector comprising said polynucleotide. One would have been motivated to and have a reasonable expectation of success to utilize the method of Brogdon to produce the immune cell of the patent because Brogdon teaches and demonstrates such methods are known and established, and the patent claims the known nucleotide sequences and immune cells for producing the CAR-expressing immune cells.
Claims 81-100 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 9, 11, 16, 25, 27-28, and 31 of copending Application No. 18/175,049 (herein after referred to as "reference application") in view of US 2016/0051651 A1 (herein after referred to as "Brogdon").
Claims 1-2, 9, and 11 of the reference application are drawn to an isolated human immune cell engineered to have (i) an inactivated or deficient endogenous gene ofRFX5 (regulatory factor X5); (ii) an inactivated or deficient endogenous gene of TRAC (T cell receptor alpha constant); and (iii) an exogenous polynucleotide encoding a chimeric antigen receptor (CAR) or a T-cell receptor (TCR),wherein the endogenous gene of B2M (Beta-2-microglobulin) in the T cell is not engineered. The claims further specify that the immune cell may be a T cell or an NK cell, the CAR or TCR recognizes CLL-1, and the CAR comprises the amino acid sequence of, for example, SEQ ID NO: 66. It is specifically noted that reference application SEQ ID NO: 66 is an exact match to instant SEQ ID NO: 32; as such, it is noted that the reference application by way of SEQ ID NO: 66 reads on the CAR of instant claims 81-92. Furthermore, it is noted that reference application CAR amino acid sequence of SEQ ID NO: 66 also renders obvious/reads on the polynucleotide of instant claims 81-93. Claims 16, 25, 27-28, and 31 of the reference application read on a method for preparing an allogeneic cell with reduced activity in inducing graft-versus-host disease (GVHD) or host rejection, comprising engineering a cell to (i) have reduced expression or activity of MHC class I by 10% to 80% as compared to a reference cell, (ii) have reduced expression or activity of MHC class II by at least 75% as compared to a reference cell, and (iii) have an exogenous polynucleotide encoding a chimeric antigen receptor (CAR) or a T-cell receptor (TCR). The claims further specify that the allogenic cell is a T cell or an NK cell, the CAR or TCR recognizes CLL-1, the CAR comprises, for example, SEQ ID NO: 66, and the CAR or TCR is introduced to the cell prior to editing of a gene. Thus, the reference application generally reads on a CAR that recognizes CLL-1, and (1) an immune cell (e.g., a T cell or an NK cell) is engineered to comprise an exogenous polynucleotide encoding said CAR and (2) a method for preparing an allogenic cell (e.g., T cell or NK cell) comprising engineering a cell to have an exogenous polynucleotide encoding said CAR. However, the reference application does not explicitly claim how said immune/allogenic cells are engineered with regard to the exogenous polynucleotide encoding the CAR. This deficiency is remedied by Brogdon.
Brogdon discloses chimeric antigen receptors (CARs) specific to CLL-1, vectors encoding the same, and recombinant cells comprising the CLL-1 CAR (Abstract). The invention pertains to a method of making a cell comprising transducing a cell, e.g., an immune effector cell, e.g., a T cell or a NK cell, with a vector of comprising a nucleic acid encoding a CAR of the invention (Paragraph 0060); the vector is selected from the group consisting of a DNA, a RNA, a plasmid, a lentivirus vector, adenoviral vector, or a retrovirus vector (Paragraph 0055). More specifically, Brogdon discloses that ex vivo procedures are well known in the art; briefly, cells are isolated from a mammal (e.g., a human) and genetically modified (i.e., transduced
or transfected in vitro) with a vector expressing a CAR of the invention (Paragraph 0756). Additionally, Brogdon notes that the mammalian recipient (of a composition comprising the CAR/CAR-modified immune cells of the invention) may be a human and the CAR-modified
cell can be autologous with respect to the recipient or, alternatively, the cells can be allogeneic, syngeneic or xenogeneic with respect to the recipient (Id.). Thus, Brogdon discloses methods of preparing CAR-modified immune cells comprising contacting the immune cells with a polynucleotide encoding the CAR (i.e., a CLL-1 specific CAR) wherein the contacting is transduction or transfection in vitro and wherein it is further noted that the polynucleotide encoding the CAR may be provided in a vector, the immune cell may be a T cell or an NK cell, and the immune cells may be autologous or allogenic. Brogdon further discloses that the CARs and CAR-modified immune cells of the invention can be used in a method of treating cancer in a subject wherein the method comprises administering to the subject a CLL-1 CAR-expressing cell (e.g., CLL-1 CART or CLL-1 CAR-expressing NK cell) of the invention such that the cancer is treated in the subject; cancers to be treated include a cancer associated with expression of CLL-1, such as a hematological cancer wherein a hematologic cancer includes but is not limited to leukemia (such as acute myelogenous leukemia, chronic myelogenous leukemia, acute lymphoid leukemia, chronic lymphoid leukemia and myelodysplastic syndrome) and malignant lymphoproliferative conditions, including lymphoma (such as multiple myeloma, non-Hodgkin's lymphoma, Burkitt's lymphoma, and small cell- and large cell follicular lymphoma), minimal residual disease, MRD, e.g., of a leukemia, e.g., of AML or MDS (Paragraph 0750).
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to prepare the immune cell comprising CLL-1 CAR of the reference application utilizing the method of Brogdon to arrive at a method for preparing an immune cell (e.g., an autologous or allogenic T cell) wherein the method comprises introducing to the immune cell a polynucleotide encoding the CLL-1 specific CAR wherein said introducing comprises, for example, in vitro transduction of said immune cell with said polynucleotide or a vector comprising said polynucleotide. One would have been motivated to and have a reasonable expectation of success to utilize the method of Brogdon to produce the immune cell of the reference application because Brogdon teaches and demonstrates such methods are known and established, and the patent claims the known nucleotide sequences and immune cells for producing the CAR-expressing immune cells.
This is a provisional nonstatutory double patenting rejection.
Art-Free Subject Matter
It is noted that full-length VH CDRs 1-3 and VL CDRs 1-3 sequences corresponding to SEQ ID NOs: 17, 18, 19, 22, 23, and 24, respectively; full-length VH and VL sequences corresponding to SEQ ID NOs: 16 and 21, respectively; full-length CAR amino acid sequence corresponding to SEQ ID NO: 32; and full-length CAR polynucleotide sequence corresponding to SEQ ID NO: 31 have all been thoroughly searched and are free of the prior art. However, the instant claims suffer from deficiencies under 35 U.S.C 112 and nonstatutory double patenting.
The closest prior art made of record but not relied upon is US 2016/0051651 A1 (herein after referred to as “Brogdon”). Brogdon teaches chimeric antigen receptors (CARs) specific
to CLL-1, vectors encoding the same, and recombinant cells comprising the CLL-1 CAR (Abstract), however Brogdon does not teach or render obvious CARs specific to CLL-1 comprising the instantly claimed VH CDRs 1-3 and VL CDRs 1-3 sequences corresponding to SEQ ID NOs: 17, 18, 19, 22, 23, and 24, respectively; full-length VH and VL sequences corresponding to SEQ ID NOs: 16 and 21, respectively; full-length CAR amino acid sequence corresponding to SEQ ID NO: 32; nor full-length CAR polynucleotide sequence corresponding to SEQ ID NO: 31.
Conclusion
Claims 81-100 are pending. Claims 81-100 are rejected. No claims are allowed.
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/ALYSSA RAE STONEBRAKER/Examiner, Art Unit 1642
/Laura B Goddard/Primary Examiner, Art Unit 1642