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 .
Priority
The instant application, filed on 06 December, 2023, is a 371 of PCT/EP2022/065596 filed on 08 June, 222.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 06, December, 2023 has been considered by the examiner.
Status of Application, Amendments, and/or Claims
The response filed on 31 July, 2024 has been entered in full. These are the amended claims of the original claim set received on 06 December, 2023. In the amendment, claims 1, 2, 4, 6, 7, 10, 12-15, 18, 21, 24, 27, 29, 31-36, 39, and 42 are amended and claims 3, 5, 8, 9, 11, 16, 17, 19, 20, 22, 23, 25, 26, 28, 30, 37, 38, 40, 41, 43, and 44 are cancelled. Therefore, claims 1, 2, 4, 6, 7, 10, 12-15, 18, 21, 24, 27, 29, 31-36, 39, 42, and 45 are pending and are the subject of this Office Action.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1, 2, 4, 6, 7, 10, 12-15, 18, 21, 24, 27, 29, 31-36, 39, 42, and 45 are rejected under 35 U.S.C. 103 as being unpatentable over Cho et al. (of record IDS 12/06/2023, NPL Cite No.1) in view of Reinhard et al. (of record IDS 12/06/2023, NPL Cite No.5) and Stadler et al. (2017) Elimination of large tumors in mice by mRNA-encoded bispecific antibodies Nature Medicine 23(7) 815-817.
In regards to claim 1 and 24 Cho teaches the treatment of xenograft mice cancer models containing breast cancer cells which express HER2 (target antigen) with CAR T cells wherein the CAR have leucine zipper tag to allows for the changing of target antigen named the zipCAR (figure 3/ pg.1431, col 1, lines 20-28). Further Cho teaches the administration of a polypeptide which binds to both the binding moiety to the CARs leucine zipper tag and the HER2 target antigen named the zipFv (the second polypeptide of the instant application) (figure 3/ pg.1431, co 1, lines 28-29).
In regards to claims 12 and 34 Cho teaches the target antigen of the zipFv can be Axl or HER2, both of which are cell surface antigens (figure 1).
In regards to claim 13 and 35 Cho teaches the zipFv being a fusion peptide of a cognate of the leucine zipper and a scFv of a target antigen (pg.1428, col 1, lines 22-25).
In regards to claims 14 and 36 Cho teaches the binding moiety of the target antigen is an scFv (an antibody fragment) (pg.1428, col 1, lines 22-25).
In regards to claim 15 Cho teaches the use of a leucine zipper and its cognate as the binding moiety for the CAR (pg.1428, col 1, lines 20-22).
In regards to claims 18 and 39 Cho teaches administering an T cell (immune effector cell) which has been genetically modified to express a CAR to the subject (pg.1431, col 1, lines 26-27).
In regards to claims 21 and 42 Cho teaches the cells expressing the target antigen are HER2+ breast cancer cells (pg.1428, col 1, lines 23-24).
Cho fails to teach the administration of a first RNA encoding a first peptide/polypeptide which is expressed in APC cells and binds to the CAR to facilitate expansion of claims 1 and 24, as well as the delivery of the second peptide/polypeptide as an RNA encoding the peptide/polypeptide also of claims 1 and 24. Cho also fails to teach the first RNA being administered as a lipoplex particle formulation of claims 2 and 27 and the first peptide/polypeptide remaining associated with the APC of claims 7 and 32. Further Cho fails to teach the second RNA being a lipid nanoparticle formulation to transfect cells of claims 4 and 29 and the second polypeptide being secreted by the transfected cells of claims 10 and 33.
Reinhard, however, in regards to claims 1 and 24 teaches administering to a subject which has been treated with a CAR and a CAR-T cell amplifying RNA vaccines (pg.3, col 2, line 13 – pg.3, col 3, line 8), to transfect APC cells in vivo, to facilitate expansion and infiltration and combat the rapid decline of CAR-T cell frequency in solid tumors (pg. 1, col 3, line 54 - pg.2, col 1, line 2).
In regards to claims 2 and 27 Reinhard teaches the delivery of the RNA which is expressed in APC cells to facilitate expansion is formulated as lipoplex particles (Figure 2A).
In regards to claims 6 and 31 Reinhard teaches the peptide/polypeptide remaining in association with the APC (pg.3, col 2, lines 10-13/ pg.7, col 2, lines 25-29).
In regards to claims 7 and 32 Reinhard teaches the peptide/polypeptide is CLDN6 which is a membrane peptide (pg.3, col 2, lines 5-9 / pg.1, col 1, lines 12-15).
Reinhard fails to teach delivery of the second peptide/polypeptide as an RNA encoding the peptide/polypeptide of claims 1 and 24, the second RNA being a lipid nanoparticle formulation to transfect cells of claims 4 and 29, and the second polypeptide being secreted by the transfected cells of claims 10 and 33.
Stadler, however, in regards to claims 1 and 24 teaches the delivery of a bispecific fusion protein in the form of an mRNA (pg.815, col 1, line 23- pg.815, col 2, line 4) to overcome problems such as poor solubility and aggregation during storage and the short half-life in serum requiring continuous delivery (pg.815, col 1, lines 8-15). Stadler also teaches intravenous injection to allow for the mRNA to be translated by the subjects’ cells (pg.815, col 2, line 25).
In regards to claims 4 and 29 Stadler teaches the mRNA encoding the bispecific antibody is a polymer/lipid based transfection reagent to ensure abundant translation (pg.815, col 2, lines 24-25).
In regards to claims 10 and 33 Stadler teaches the bispecific antibody which is encoded by the mRNA is secreted into to bloodstream (pg.815, col 2, lines 26-28 / Figure 2a).
Claim 45 refers to kit which comprises components as outlined in method claims 1 and 24 without listing other components therefore the kit does not preclude the methods.
Thus, Cho discloses a method of developing a CAR-T cell with a binding moiety which allows for the swapping of target antigen by the delivery of a fusion peptide which contains both the binding moiety of the CAR as well as the binding moiety for the target antigen for versatility in disease applicability, Reinhard teaches the delivery of RNA lipoplexes encoding a membrane bound peptide in APCs which binds to the CAR to improve function and facilitate CART cell expansion, and Stadler teaches the delivery of mRNA in a lipid formulation to encode for the in vivo expression of a bispecific antibody which can be secreted into the blood stream to overcome manufacturing and pharmacological obstacles to systemic delivery of bispecific antibodies. Therefore, a person of ordinary skill in the art before the effective filing date of the claimed invention would have found it obvious to combine the teachings of Cho, Reinhard, and Stadler with a reasonable expectation of success to develop a method of treat a disease characterized by cells expressing a target antigen , wherein the CART cell is exposed first to APCs expressing a peptide to facilitate expansion of the cells, and then is further designed to be universal CAR by making the binding region of the CAR a peptide tag to facilitate delivery of a bispecific peptide to allow for versatility in target antigen without needed to introduce more CARs for treatment, and wherein the bispecific peptide is delivered as an RNA encoding the peptide to improve manufacturing and increase half-life in the bloodstream for a more effective treatment.
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.
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Claims 1, 2, 18, 24, 27, and 39 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 28, 31, 41, 44, 48, 55, 58, 59, and 70 of copending Application No. 17/310,463 (06/02/2026 claim set) in view of Reinhard et al., Cho et al., and Stadler et al.
Claims 48 of the copending application which is dependent on claims 1, 28, 31, 41, and 44 recites claim to a method of stimulating an immune response in a subject by delivery of effector cells expressing a CAR and further wherein the subject is administered a cognate antigen (also recited in claim 70) and wherein the delivery method is an RNA encoding the cognate antigen. Which significantly overlaps with claims 1, 18, 24, and 39 of the instant application (note instant claims 18 and 39 recite claim to administering immune effector cells genetically modified to express a CAR).
Claim 59 of the copending application which is dependent on claims 1, 28, 31, 41, 44, 55, and 58 further recites that the nucleic acid encoding the cognate antigen is formulated in a delivery vehicle (claim 55), wherein the delivery vehicle comprises at least one cationic lipid (claim 58), and the cationic lipid forms a complex with and/or encapsulates the nucleic acid. Which significantly overlaps with claims 2 and 27 of the instant application.
The copending application fails to teach the cognate antigen being expressed in antigen presenting cells and facilitating expansion when bound to the cell containing the CAR. Further the copending application fails to teach the administration of a second RNA which encodes a peptide which comprises a binding moiety for the CAR and a binding moiety to the target antigen, and wherein the second peptide is expressed in the cells of the subject.
Reinhard however teaches that binding the CAR to its target antigen can lead to expansion and further expressing the RNA exclusively in APCs as outlined above. Reinhard fails to teach the administration of a second RNA which encodes a peptide which comprises a binding moiety for the CAR and a binding moiety to the target antigen, and wherein the second peptide is expressed in the cells of the subject.
Cho however, teaches the treatment of xenograft mice cancer models with breast cancer cells which express HER2 (target antigen) with CAR T cells wherein the CAR expresses have leucine zipper tag to allows for the changing of target antigen named the zipCAR and the administration of a polypeptide which binds to both the binding moiety to the CARs leucine zipper tag and the HER2 target antigen named the zipFv as outlined above. Cho fails to teach the delivery of the second peptide/polypeptide as an RNA encoding the peptide/polypeptide of instant claims 1 and 24.
Stadler, however, in regards to claims 1 and 24 teaches the delivery of a bispecific fusion protein in the form of an mRNA to overcome problems such as poor solubility and aggregation during storage and the short half-life in serum requiring continuous delivery, as well as intravenous injection to allow for the mRNA to be translated by the subjects’ cells as outlined above.
Thus the copending application teaches a method of stimulating an immune response in a subject by delivery of effector cells expressing a CAR and further wherein the subject is administered a RNA lipid complex which encodes for a cognate antigen, Reinhard teaches that binding to a cognate antigen can facilitate immune effector cell expansion and further teaches how to express the RNA in antigen presenting cells, Cho teaches the administration of another fusion protein which binds to the CAR and the target antigen allowing for the development of a universal CAR system and Stadler teaches administering the bispecific fusion protein as an RNA would improve its half-life and manufacturing process. Therefore, a person of ordinary skill in the art before the effective filling date of the claimed invention would have found it obvious to combine the methods of the copending application with the teachings of Reinhard, Cho, and Stadler with a reasonable expectation of success to adapt the method of stimulating an immune response with CAR cells and a cognate antigen with the goals of further developing a universal CAR.
This is a provisional nonstatutory double patenting rejection.
Claims 1, 2, 24, and 27 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 30, 37, 39, 45, 47, 49, 51, 53, 76, 79, and 81 of copending Application No. 18/717,782 (12/09/2024 claim set) in view of Cho et al. and Stadler et al.
Claim 37 of the copending application which depends on claims 1 and 30 recites claim to a method of treating a solid tumor cancer by administering immune effector cells expressing a CAR molecule to a the target antigen CLDN6 (claim 1) and further contacting the immune effector cells with a cognate antigen molecule which bind to CLDN6 to induce expansion and/or activation of the immune effector cell in vivo or ex vivo (claim 30), and further where the cognate antigen molecule is introduced by a nucleic acid encoding the cognate (claim 34) and the nucleic acid molecule is an RNA (claim 37) This significantly overlaps with claims 1 and 24 of the instant application.
Claim 39 of the copending application which depends on claim 1 further teaches that after the systemic delivery of the RNA encoding the cognate antigen the cognate antigen is expressed in APCs. This significantly overlaps with claims 1 and 24 of the instant application.
Claim 49 of the copending application which depends on claims 1, 30, 34, 45, and 47 further recites the nucleic acid encoding the cognate receptor is formulated in a delivery vehicle that comprises at least one cationic lipid and wherein the lipid form a complex with and/or encapsulates the nucleic acid. This significantly overlaps with claims 2 and 27 of the instant application.
Claim 51 of the copending application which depends on claims 1, 30, and 34 further recites that the nucleic acid encoding the cognate antigen is formulated in lipoplexes. This significantly overlaps with claims 2 and 27 of the instant application.
Claims 53, 76, 79, and 81 of the copending application recite claim to a composition of medical preparation containing the components outlined above and therefore do not preclude the method.
It is noted that claim 39 of the copending teaches the limitation of the antigen being expressed in APCs of instant claims 1 and 24 and claim 37 of the copending application teaches the limitation of the antigen binding to the CART cells to facilitate expansion of instant claims 1 and 24, Further claims 39 and 37 of the copending application do not depend of each other, however, as outlined by Reinhard above these claims can be used in combination with each other to meet the full scope of limitations of instant claims 1 and 24.
The patent fails to teach the administration of a second RNA which encodes a peptide which comprises a binding moiety for the CAR and a binding moiety to the target antigen, and wherein the second peptide is expressed in the cells of the subject of claim 1 and 24.
Cho however, teaches the treatment of xenograft mice cancer models with breast cancer cells which express HER2 (target antigen) with CAR T cells wherein the CAR expresses have leucine zipper tag to allows for the changing of target antigen named the zipCAR and the administration of a polypeptide which binds to both the binding moiety to the CARs leucine zipper tag and the HER2 target antigen named the zipFv as outlined above.
Cho fails to teach the delivery of the second peptide/polypeptide as an RNA encoding the peptide/polypeptide of instant claims 1 and 24.
Stadler, however, in regards to claims 1 and 24 teaches the delivery of a bispecific fusion protein in the form of an mRNA to overcome problems such as poor solubility and aggregation during storage and the short half-life in serum requiring continuous delivery, as well as intravenous injection to allow for the mRNA to be translated by the subjects’ cells as outlined above.
Thus the copending application teaches a method of treating a solid tumor cancer in a subject by delivery of effector cells expressing a CAR and further wherein the subject is further administered a RNA lipid complex which encodes for a cognate antigen, Reinhard teaches the combination of the cognate antigen being expressed on antigen presenting cells and facilitating immune effector cell expansion, Cho teaches the administration of another fusion protein which binds to the CAR and the target antigen allowing for the development of a universal CAR system and Stadler teaches administering the bispecific fusion protein as an RNA would improve its half-life and manufacturing process. Therefore, a person of ordinary skill in the art before the effective filling date of the claimed invention would have found it obvious to combine the methods of the copending application with the teachings of Reinhard, Cho, and Stadler with a reasonable expectation of success to adapt the method of stimulating an immune response with CAR cells and a cognate antigen with the goals of further developing a universal CAR.
This is a provisional nonstatutory double patenting rejection.
Claims 1, 18, 24, and 39 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 10, 12, 13, 26, 35-37, 43, 44 and 46-48 of copending Application No. 17/757,195 (03/03/2026 claim set) in view of Reinhard et al. , Cho et al. and Stadler et al.
Claim 10 of the copending application recites claim to a method of treating a subject having a solid cancer associated with expression of a tumor antigen comprising providing immune effector cell genetically modified to express an antigen receptor, the antigen receptor being targeted to the tumor antigen and administering an polynucleotide encoding the antigen wherein administration result in expansion of the immune effector cells genetically modified to express the antigen receptor in the subject. Claims 35 and 36 of the copending application which depend on claim 10 recite the antigen receptor can be a CAR. Further claim 37 of the copending application recite the polynucleotide encoding the antigen is an RNA. These claims significantly overlap with claims 1 and 24 of the instant application.
Claims 12 and 13 of the copending application which depend on claim 10 further recite that the immune effector cells expressing the antigen receptor can be made ex vivo or in vivo, which significantly overlaps with claims 18 and 39 of the instant application.
Claim 43 of the copending application recites claim a method of treating a subject having a solid cancer associated with expression of a tumor antigen comprising providing immune effector cell genetically modified to express an antigen receptor, the antigen receptor being targeted to the tumor antigen and administering an polynucleotide encoding the antigen wherein administration result in expansion of the immune effector cells genetically modified to express the antigen receptor in the subject. Claim 44 of the copending application which depends on claim 43 further recites the polynucleotide encoding the antigen is an RNA. Claim 48 of copending application which depends on claims 43, 46, and 47 further recites the antigen receptor is a CAR. These claims significantly overlap with claims 1 and 24 of the instant application.
The copending application fails to teach the antigen being expressed in antigen presenting cells. Further the copending application fails to teach the administration of a second RNA which encodes a peptide which comprises a binding moiety for the CAR and a binding moiety to the target antigen, and wherein the second peptide is expressed in the cells of the subject.
Reinhard however teaches expressing the RNA exclusively in APCs as outlined above. Reinhard fails to teach the administration of a second RNA which encodes a peptide which comprises a binding moiety for the CAR and a binding moiety to the target antigen, and wherein the second peptide is expressed in the cells of the subject.
Cho however, teaches the treatment of xenograft mice cancer models with breast cancer cells which express HER2 (target antigen) with CAR T cells wherein the CAR expresses have leucine zipper tag to allows for the changing of target antigen named the zipCAR and the administration of a polypeptide which binds to both the binding moiety to the CARs leucine zipper tag and the HER2 target antigen named the zipFv as outlined above. Cho fails to teach the delivery of the second peptide/polypeptide as an RNA encoding the peptide/polypeptide of instant claims 1 and 24.
Stadler, however, in regards to claims 1 and 24 teaches the delivery of a bispecific fusion protein in the form of an mRNA to overcome problems such as poor solubility and aggregation during storage and the short half-life in serum requiring continuous delivery, as well as intravenous injection to allow for the mRNA to be translated by the subjects’ cells as outlined above.
Thus the copending application teaches a method of treating a solid tumor cancer in a subject by delivery of effector cells expressing a CAR and further wherein the subject is further administered a RNA lipid complex which encodes for the antigen, Reinhard teaches the antigen being expressed on antigen presenting cells, Cho teaches the administration of another fusion protein which binds to the CAR and the target antigen allowing for the development of a universal CAR system and Stadler teaches administering the bispecific fusion protein as an RNA would improve its half-life and manufacturing process. Therefore, a person of ordinary skill in the art before the effective filling date of the claimed invention would have found it obvious to combine the methods of the copending application with the teachings of Reinhard, Cho, and Stadler with a reasonable expectation of success to adapt the method of stimulating an immune response with CAR cells and an antigen with the goals of further developing a universal CAR.
This is a provisional nonstatutory double patenting rejection.
Claims 1, 2, 6, 18, 24, 27, 31, and 39 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 14, 18, 28, and 29 of U.S. Patent No. 12,186,275 in view of Reinhard et al., Cho et al. and Stadler et al.
Claim 1 of the patent recites claim to a method of stimulating an immune response to target a cell population or tissue expressing an antigen in a mammal, comprising transfecting T cells with a nucleic acid encoding a CAR targeted to the antigen wherein the T cells are transfected in vivo and administering a second nucleic acid which is an RNA disposed in liposomes and encodes the antigen.
Claim 12 of the patent which depends on claim 1 further recites the second nucleic acid is administered systemically.
Claim 14 of the patent which depends on claim 12 further recites the antigen encoded by the second nucleic acid is expressed in antigen presenting cells.
Claim 18 of the patent which depends on claim 1 further recites the second nucleic acid when expressed in the cells of the mammal bind to the T cells expressing the CAR resulting in stimulation, priming and/or expansion of the T cells.
Claim 28 of the patent recites claim to a method of treating a mammal that has a disease, disorder, or condition associated with expression or elevated expression of an antigen, comprising transfecting T cells with a nucleic acid encoding a CAR targeted to the antigen wherein the T cells are transfected in vivo and administering a second nucleic acid which is an RNA disposed in liposomes and encodes the antigen.
Claim 29 of the patent which depends on claim 28 further recites the disease, disorder, or condition is cancer.
These claims significantly overlap with claims 1 and 24 of the instant application which recites a method of treating a disease disorder or condition characterized by cell expressing a target antigen comprising providing a CAR and administering a second RNA which encoding the antigen.
Further these claims significantly overlap with claims 18 and 39 of the instant application which recites the CAR cells can be made ex vivo or in vivo. These claims also significantly overlap with instant claims 2 and 27 which wherein the cells are formulated as lipoplex formulations.
It is noted that claim 12 of the patent teaches the limitation of the antigen being expressed in APCs of instant claims 1 and 24 and claim 18 of the patent teaches the limitation of the antigen binding to the CART cells to facilitate expansion of instant claim 1 and 24, Further claims 12 and 18 of the patent do not depend of each other, however, as outlined by Reinhard above these claims can be used in combination with each other to meet the full scope of limitations of instant claims 1 and 24.
The patent fails to teach the administration of a second RNA which encodes a peptide which comprises a binding moiety for the CAR and a binding moiety to the target antigen, and wherein the second peptide is expressed in the cells of the subject of claim 1 and 24.
Cho however, teaches the treatment of xenograft mice cancer models with breast cancer cells which express HER2 (target antigen) with CAR T cells wherein the CAR expresses have leucine zipper tag to allows for the changing of target antigen named the zipCAR and the administration of a polypeptide which binds to both the binding moiety to the CARs leucine zipper tag and the HER2 target antigen named the zipFv as outlined above.
Cho fails to teach the delivery of the second peptide/polypeptide as an RNA encoding the peptide/polypeptide of instant claims 1 and 24.
Stadler, however, in regards to claims 1 and 24 teaches the delivery of a bispecific fusion protein in the form of an mRNA to overcome problems such as poor solubility and aggregation during storage and the short half-life in serum requiring continuous delivery, as well as intravenous injection to allow for the mRNA to be translated by the subjects’ cells as outlined above.
Thus the U.S. Patent teaches a method of stimulating an immune response in a subject by in vivo transfection of effector cells to express a CAR and further wherein the subject is further administered a RNA liposome complex which encodes for an antigen, Reinhard teaches the combination of the cognate antigen being expressed on antigen presenting cells and facilitating immune effector cell expansion, Cho teaches the administration of another fusion protein which binds to the CAR and the target antigen allowing for the development of a universal CAR system and Stadler teaches administering the bispecific fusion protein as an RNA would improve its half-life and manufacturing process. Therefore, a person of ordinary skill in the art before the effective filling date of the claimed invention would have found it obvious to combine the methods of the copending application with the teachings of Reinhard, Cho, and Stadler with a reasonable expectation of success to adapt the method of stimulating an immune response with CAR cells and a cognate antigen with the goals of further developing a universal CAR.
Claims 1, 2, 18, 24, 27, and 39 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1,6, 9, 11, 17, and 18 of U.S. Patent No. 10,799,534 in view of Reinhard et al., Cho et al. and Stadler et al.
Claim 1 of the patent recites claim to a method of stimulating an immune response to target a cell population or tissue expressing an antigen in a mammal, consisting of transfecting administering T cell which have been genetically modified to express CAR targeted to the antigen and administering a nucleic acid which is an RNA disposed in liposomes and encodes the antigen.
Claim 6 of the patent which depends on claim 1 further recites the nucleic acid encoding the antigen is expressed in the cells of the mammal to provide the antigen.
Claim 9 of the patent which depends on claim 1 further recites the antigen encoded by the second nucleic acid is expressed in antigen presenting cells.
Claim 11 of the patent which depends on claim 1 further recites the second nucleic acid when expressed in the cells of the mammal bind to the T cells expressing the CAR resulting in stimulation, priming and/or expansion of the T cells.
Claim 17 of the patent recites claim to a method of treating a mammal that has a disease, disorder, or condition associated with expression or elevated expression of an antigen, consisting of transfecting administering T cell which have been genetically modified to express CAR targeted to the antigen and administering a nucleic acid which is an RNA disposed in liposomes and encodes the antigen.
Claim 18 of the patent which depends on claim 17 further recites the disease, disorder, or condition is cancer.
These claims significantly overlap with claims 1 and 24 of the instant application which recites a method of treating a disease disorder or condition characterized by cell expressing a target antigen comprising providing a CAR and administering a second RNA which encoding the antigen.
Further these claims significantly overlap with claims 18 and 39 of the instant application which recites the CAR cells can be made ex vivo or in vivo. These claims also significantly overlap with instant claims 2 and 27 which wherein the cells are formulated as lipoplex formulations.
It is noted that claim 9 of the patent teaches the limitation of the antigen being expressed in APCs of instant claims 1 and 24 and claim 11 of the patent teaches the limitation of the antigen binding to the CART cells to facilitate expansion of instant claim 1 and 24, Further claims 9 and 11 of the patent do not depend of each other, however, as outlined by Reinhard above these claims can be used in combination with each other to meet the full scope of limitations of instant claims 1 and 24.
The patent fails to teach the administration of a second RNA which encodes a peptide which comprises a binding moiety for the CAR and a binding moiety to the target antigen, and wherein the second peptide is expressed in the cells of the subject of claim 1 and 24.
Cho however, teaches the treatment of xenograft mice cancer models with breast cancer cells which express HER2 (target antigen) with CAR T cells wherein the CAR expresses have leucine zipper tag to allows for the changing of target antigen named the zipCAR and the administration of a polypeptide which binds to both the binding moiety to the CARs leucine zipper tag and the HER2 target antigen named the zipFv as outlined above.
Cho fails to teach the delivery of the second peptide/polypeptide as an RNA encoding the peptide/polypeptide of instant claims 1 and 24.
Stadler, however, in regards to claims 1 and 24 teaches the delivery of a bispecific fusion protein in the form of an mRNA to overcome problems such as poor solubility and aggregation during storage and the short half-life in serum requiring continuous delivery, as well as intravenous injection to allow for the mRNA to be translated by the subjects’ cells as outlined above.
Thus the U.S. Patent teaches a method of stimulating an immune response in a subject by delivery of effector cells expressing a CAR and further wherein the subject is further administered a RNA liposome complex which encodes for an antigen, Reinhard teaches the combination of the cognate antigen being expressed on antigen presenting cells and facilitating immune effector cell expansion, Cho teaches the administration of another fusion protein which binds to the CAR and the target antigen allowing for the development of a universal CAR system and Stadler teaches administering the bispecific fusion protein as an RNA would improve its half-life and manufacturing process. Therefore, a person of ordinary skill in the art before the effective filling date of the claimed invention would have found it obvious to combine the methods of the copending application with the teachings of Reinhard, Cho, and Stadler with a reasonable expectation of success to adapt the method of stimulating an immune response with CAR cells and a cognate antigen with the goals of further developing a universal CAR.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DASIA A ALDARONDO whose telephone number is (571)272-1977. The examiner can normally be reached on Monday-Thursday from 8am to 6pm.
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/D.A.A/Examiner, Art Unit 1647 /JOANNE HAMA/Supervisory Patent Examiner, Art Unit 1647
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