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 .
Claims 1-8, 12, 14-25, 27, 35, 37, 46, and 55-59 are pending and currently under consideration.
Claim Objections
Claim 14 is objected to because of an apparent typographical error. Claims 14 recites “…does not specifically binding TCR.” The term “binding” should be replaced by “bind.” Proper correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 3-8, 12, 15-17, and 19-23 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 3-5, 16, and 17 are rejected because claims 3-5 and 17 recites “…wherein the virus endoplasmic reticulum resident protein is….” There is insufficient antecedent basis for ” the virus endoplasmic reticulum resident protein” in the claims.
Claims 6-8, 12, and 19-23 are rejected because it is unclear how, or if, limitations in parenthesis following “e.g.” or “including” limit the claims. The metes-and-bounds of the claims are unclear.
Claims 7, 8, and 12 because claim 7 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 the source of a product and, accordingly, the identification/description is indefinite.
Claim 15 is rejected because it is unclear how, or if, limitations following the term “preferably” limit the claim. The metes-and-bounds of the claim are unclear.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1, 7, 8, 25, 27, 35, 55, and 56 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Burrone et al (WO 2012/070008 A2; 5/31/2012; 8/1/23 IDS).
Burrone et al teaches “degradins” (line 18 on page 8, in particular) for inactivation of target proteins, wherein degradins are chimeric proteins comprising (i) an endoplasmic reticulum-associated degradation (ERAD) mechanism (lines 1-3 on page 9, in particular) such as a portion of SEL1L and (ii) a targeting domain that binds a target protein (lines 23-26 on page 7 and lines 2-6 on page 8, in particular). Burrone et al further teaches said degradins wherein the targeting domain is an scFv (line 16 on page 12, in particular). Burrone et al further teaches said degradins wherein the target protein is a pathogenic protein, a tumor-associated protein, a virus-associated protein, or a protein associated with neurodegenerative disease (pages 24-25, in particular). Burrone et al teaches nucleic acid expression vectors encoding said degradins (page 20 and Figure 1, in particular), expression of said degradins by said vectors in engineered host cells (lines 8-12 on page 21, in particular), and wherein promoters are uses to direct expression of said vectors in a tissue specific manner (line 5 on page 23 and paragraph spanning pages 27-28, in particular). Burrone et al further teaches pharmaceutical compositions comprising said nucleic acid vectors encoding degradins that can be administered to a patient (lines 1-16 on page 28, in particular).
Claim Rejections - 35 USC § 102
Claim(s) 1, 2, 8, 12, 14 , 25, 27, 35, 55, and 56 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Coffield et al (Nature Biotechnology, 2003, 21(11): 1321-1327).
Coffield et al teaches “degrakine” for inactivation of a chemokine receptor protein, wherein the degrakine is a chimeric protein that comprises (i) an endoplasmic reticulum-associated degradation (ERAD) mechanism that is VpuC (C terminal region of an HIV-1 protein that specifically targets CD4 for degradation in the ER by binding with b-TrCP-Skp1 protein, which leads to CD4 ubiquitination and degradation) and (ii) SDF-1a (CXCL12) that targets the chemokine receptor CXCR4 that is used to “harness Vpu’s proteolytic targeting capability to degrade new receptors” (right column on page 1321 and Figure 1, in particular). In particular regards to claim 6, Coffield et al further teaches VpuC of the degrakine recruits proteosome (Figure 1, in particular). One of skill in the art would recognize CXCR4 is an immune function-related protein and an immune stimulatory/co-stimulatory molecule. One of skill in the art would further recognize SDF-1a (CXCL12) binds CXCR4 and does not specifically bind TCR. Coffield et al further teaches a nucleic acid vector encoding the derakine under the control of a promoter that expresses the derakine in engineered host cells (Figure 1, in particular).
Claim Rejections - 35 USC § 102
Claim(s) 1, 2, 8, 12, 14, 15 , 25, 27, 35, 55, and 56 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Sester et al (Journal of Virology, 2013, 87(11): 6104-6717; 8/1/23 IDS).
Sester et al teaches “EKE”, which is a chimeric protein comprising luminal and cytoplasmic domains of E3/19K flanking MHC-I Kd transmembrane domain that comprises (i) an endoplasmic reticulum-associated degradation (ERAD) mechanism that is a cytoplasmic domain of E3/19K and (ii) a luminal domain of E3/19K that targets MHC-I and MHC-I-related chain A and B molecules (Abstract and Figure 1, in particular). One of skill in the art would recognize MHC-I-related chain A and B are immune function-related proteins and antigen-presenting molecules that are not TCR. Sester et al further teaches expression vectors comprising promoters and nucleic acids encoding EKE expressed in recombinant host cells (right column on page 6105 and paragraph spanning pages 6106-6107, in particular). Sester et al further teaches “EEE”, which comprises (i) an endoplasmic reticulum-associated degradation (ERAD) mechanism that is a cytoplasmic domain of E3/19K and (ii) a luminal domain of E3/19K that targets MHC-I-related chain A and B greatly downregulates both MICA/B and HLA cell surface expression (Abstract and Figures 1, 7, and 10, in particular).
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, 7, 8, 12, 14, 15, 18-25, 27, 35, 37, 55, and 56 are rejected under 35 U.S.C. 103(a) as being unpatentable over Torikai et al (Blood, 2013, 122(8): 1341-1349) in view of Ma et al (WO 2017/112877 A1; 6/29/17), Burrone et al (WO 2012/070008 A2; 5/31/2012; 8/1/23 IDS), and Sester et al (Journal of Virology, 2013, 87(11): 6104-6717; 8/1/23 IDS).
Torikai et al teaches therapies using donor-derived (allogenic) cells are advantageous compared to patient-derived cells because the ability to manufacture and validate therapeutic and fully-functional cell preparations in advance improves safety, consistency, and availability (left column on page 1341, in particular). However, Torikai et al teaches a challenge of using allogenic cells in a therapy of a patient is immune responses to the infused cells by due to host-derived T-cells of the patient recognizing mismatched HLAs present on the allogenic cells, as compared to HLAs of the patient (left column on page 1341, in particular). Torikai et al further suggests avoiding such an immune response by eliminating expression of HLAs on donor-derived cells (paragraph spanning columns on page 1341, in particular). Torikai et al further discusses means of reducing HLA expression on cells to escape T-cell recognition include using viral proteins to inhibit HLA folding and surface display, using Cre-LoxP to disrupt HLA class I expression, using siRNA to target HLA heavy chains, and using a nuclease to target HLA-A locus (right column on page 1341, in particular). Torikai et al such TCR-edited T cells ameliorate graft-versus-host disease (left column on page 1345, in particular).
Torikai et al does not specifically teach a chimeric protein construct comprising an ERAD mechanism protein binding domain and a targeting domain. However, these deficiencies are made up in the teachings of Ma et al, Burrone et al, and Sester et al.
Ma et al teaches a method of treating cancer comprising administering a cell comprising a chimeric antigen receptor (lines 1-9 on page 3, in particular). Ma et al further teaches said cell expresses the chimeric antigen receptor using polynucleotide bicistronic or multicistronic expression vectors comprising expression control sequences operatively linked to sequences to be expressed within the cell, such as a T-cell, using proteolytic cleavage sites (encoding cleavage peptide/linker) between genes (paragraph spanning pages 24-25 and lines 12-24 on page 25, in particular).
Burrone et al teaches “degradins” (line 18 on page 8, in particular) for inactivation of target proteins, wherein degradins are chimeric proteins comprising (i) an endoplasmic reticulum-associated degradation (ERAD) mechanism (lines 1-3 on page 9, in particular) such as a portion of SEL1L and (ii) a targeting domain that binds a target protein (lines 23-26 on page 7 and lines 2-6 on page 8, in particular). Burrone et al further teaches said degradins wherein the targeting domain is an scFv (line 16 on page 12, in particular). Burrone et al further teaches said degradins wherein the target protein is a pathogenic protein, a tumor-associated protein, a virus-associated protein, or a protein associated with neurodegenerative disease (pages 24-25, in particular). Burrone et al teaches nucleic acid expression vectors encoding said degradins (page 20 and Figure 1, in particular), expression of said degradins by said vectors in engineered host cells (lines 8-12 on page 21, in particular), and wherein promoters are uses to direct expression of said vectors in a tissue specific manner (line 5 on page 23 and paragraph spanning pages 27-28, in particular). Burrone et al further teaches pharmaceutical compositions comprising said nucleic acid vectors encoding degradins that can be administered to a patient (lines 1-16 on page 28, in particular).
Sester et al teaches “EKE”, which is a chimeric protein comprising luminal and cytoplasmic domains of E3/19K flanking MHC-I Kd transmembrane domain that comprises (i) an endoplasmic reticulum-associated degradation (ERAD) mechanism that is a cytoplasmic domain of E3/19K and (ii) a luminal domain of E3/19K that targets MHC-I and MHC-I-related chain A and B molecules that targets MHC-I-related chain A and B downregulates both MICA/B and HLA cell surface expression (Abstract and Figures 1, 7, and 10, in particular). One of skill in the art would recognize MHC-I-related chain A and B are immune function-related proteins and antigen-presenting molecules that are not TCR. Sester et al further teaches expression vectors comprising promoters and nucleic acids encoding EKE expressed in recombinant host cells (right column on page 6105 and paragraph spanning pages 6106-6107, in particular). Sester et al further teaches “EEE”, which comprises (i) an endoplasmic reticulum-associated degradation (ERAD) mechanism that is a cytoplasmic domain of E3/19K and (ii) a luminal domain of E3/19K that targets MHC-I-related chain A and B greatly downregulates both MICA/B and HLA cell surface expression (Abstract and Figures 1, 7, and 10, in particular).
One of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform a combined method of treating a patient with cancer comprising administering an allogenic cell of Ma et al comprising a chimeric antigen receptor of Ma et al, wherein the cell comprises a multicistronic vector of Ma et al comprising a sequence encoding the chimeric antigen receptor driven by a expression control sequence linked via a sequence encoding a cleavable linker to a sequence encoding a protein that reduces surface expression of HLA on the allogenic cell (such as “EKE” and “EEE”), resulting in an allogenic cell expressing a therapeutic chimeric antigen receptor and a protein that reduces surface expression of HLA on the allogenic cell because Torikai et al teaches therapies using donor-derived (allogenic) cells are advantageous compared to patient-derived cells because the ability to manufacture and validate therapeutic and fully-functional cell preparations in advance improves safety, consistency, and availability (left column on page 1341, in particular), Torikai et al teaches a challenge of using allogenic cells in a therapy of a patient is immune responses to the infused cells due to host-derived T-cells of the patient recognizing mismatched HLAs present on the allogenic cells (left column on page 1341, in particular), Torikai et al suggests avoiding such an immune response by eliminating expression of HLAs on donor-derived cells (paragraph spanning columns on page 1341, in particular), and Sester et al teaches “EKE” and “EEE” as two proteins that reduces HLA surface expression on cells expressing EKE or EEE. This is an example of some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to combine prior art reference teachings to arrive at the claimed invention.
Further, one of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform said combined method wherein, in place of “EKE” or “EEE” the sequence encoding a protein that reduces surface expression of HLA of the combined method encodes a chimeric protein comprising the luminal and transmembrane domain of “EEE” and SEL1L of Burrone et al substituted in place of the cytoplasmic region of “EEE” because both the cytoplasmic region of EEE and SEL1L of Burrone et al have been shown to function by targeting proteins to the endoplasmic reticulum. This is an example of a simple substitution of one known element for another to obtain predictable results.
Alternatively, one of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform said combined method wherein, in place of “EKE” or “EEE” the sequence encoding a protein that reduces surface expression of HLA of the combined method encodes a degrading of Burrone et al comprising an scFv that specifically binds HLA as the targeting mechanism and SEL1L of Burrone et al as the ERAD mechanism because the combined method intends to reduce surface expression of HLA and degradins targeting HLA would reduce surface expression of HLA by targeting HLA for degradation. This is an example of some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to combine prior art reference teachings to arrive at the claimed invention.
Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, absent unexpected results.
Claim Rejections - 35 USC § 103
Claim(s) 1, 2, 7, 8, 12, 14, 15, 18-25, 27, 35, 37, 46, and 55-59 is/are rejected under 35 U.S.C. 103 as being unpatentable over Torikai et al (Blood, 2013, 122(8): 1341-1349) in view of Ma et al (WO 2017/112877 A1; 6/29/17), Burrone et al (WO 2012/070008 A2; 5/31/2012; 8/1/23 IDS), and Sester et al (Journal of Virology, 2013, 87(11): 6104-6717; 8/1/23 IDS) as applied to claims 1, 2, 7, 8, 12, 14, 15, 18-25, 27, 35, 37, 55, and 56 above, and further in view of Levine et al (Molecular Therapy: Methods & Clinical Development, 2017, 4: 92-101).
Teachings of Torikai et al, Ma et al, Burrone et al, and Sester et al are discussed above.
Torikai et al, Ma et al, Burrone et al, and Sester et al do not specifically teach a kit comprising chimeric antigen receptor-expressing T-cells (CAR-T cells) of the combined method wherein the cells are in a pharmaceutically acceptable medium. However, these deficiencies are made up in the teachings of Levine et al.
Levine et al teaches CAR-T cells are cryopreserved in infusible medium (same as “pharmaceutically acceptable medium”) and transported frozen to centers to treat patients (right column on page 93, in particular).
One of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to generate a kit comprising the CAR-T cells of the combined method cryopreserved in infusible medium to ship frozen to centers to treat patients in order to deliver cells of the combined method to patients for treatment because Levine et al teaches CAR-T cells are cryopreserved in infusible medium (same as “pharmaceutically acceptable medium”) and transported frozen to centers to treat patients (right column on page 93, in particular). Further, generating a “kit” for a given method provides two services: 1) a variety of different reagents have been assembled and pre-mixed specifically for a defined set of experiments. Thus, one need not purchase gram quantities of numerous different reagents when each of which may be needed in only microgram amounts, when beginning a series of experiments. When one considers all of the unused chemicals that typically accumulate in weighing rooms, desiccators, and freezers, one quickly realizes that it is actually far more expensive for a small number of users to prepare most buffer solutions from the basic reagents. In actuality, a kit format saves money and resources for everyone by dramatically reducing waste. 2) The other service provided in a kit is quality control. Therefore, it would have been prima facie obvious to one having ordinary skill in the art at the time the invention was made to combine the reagents of a method into a kit format since a kit provides a quality control, saves money, and saves resources. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, absent unexpected results.
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, 8, 12, 14-15, 18-25, 27, 35, 37, 46, and 55-59 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 and 13-20 of copending Application No. 18/293291 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the pending claims are drawn to products that are species of the instant claims and methods of using said products (see module “(3)” of copending claim 1 and copending dependent claims, in particular).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
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/SEAN E AEDER/Primary Examiner, Art Unit 1642