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 .
Application Status
The amendment filed May 3, 2024 is acknowledged. Claims 103-122 are pending and under examination.
Specification
The use of the term TALEN® and MegaTALTM which are trade names or marks used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 103-112, 118 and 120 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 103 recites “A composition for selectively modifying… wherein the composition is administered to a heterologous mixture…” Claim 103 is directed to a composition, i.e., a product, but then also recites the active step of “administering”. A single claim which claims both a product and the method steps of using the product is indefinite. See MPEP 2173.05(p).II. In this case, “administering to a heterologous mixture of cells” is not merely a capability of the composition, but instead is directed to actions of an individual using the composition.
Claims 104-112 are rejected for depending from claim 103 and not remedying the indefiniteness.
Claims 107, 109, 118 and 120 contains the trademark/trade name megaTAL, TALEN and/or TALENs. 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 nucleases that comprise a transcription activator-like effector domain and, accordingly, the identification/description is indefinite. Although TALEN is an acronym for transcription activator-like effector nucleases, and megaTAL is used to describe a fusion protein between a transcription activator-like effector domain and a meganuclease domain, they are still trademarked terms, rendering the claims indefinite.
To remedy the indefiniteness, it is suggested to delete “(TALENs)” from the claims. It is suggested to delete “megaTAL” from each of the claims and instead use only SEQ ID NOs for at least claims 107 and 118.
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 r-e 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 103-106 and 108-112 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-25 of U.S. Patent No. 11566061. Claims 105, 109 are rejected in view of Saltzman (US 20170283830 A1, priority to February 16, 2016). Claims 107-108 is rejected in view of Stephan (WO 2014153114 A1). Claim 110 is rejected in view of Stasi (Stasi et al., Blood (2009), 113: 6392-6402).
Patented claim 19 recites A composition, comprising… an effective amount of a nanoparticle, wherein the nanoparticle comprises (i) a polynucleotide encoding a T cell receptor (TCR) that specifically binds the vaccine antigen (i.e., a nucleic acid); and (ii) a binding fragment of an anti-CD4 or anti-CD8 antibody exposed on the surface of the nanoparticle (i.e., an antibody). Patented claims 22-23 recite wherein the polynucleotide is encapsulated within a positively-charged polymer matrix, which is PBAE. Patented claims 24-25 recite wherein the positively-charged polymer matrix is surrounded by a negatively-charged coating, which comprises polyglutamic acid (PGA). Thus, patented claim 25 encompasses a nanoparticle comprising a nucleic acid within a positively-charged polymer and surrounded by the negatively-charged PGA and having an antibody exposed on the surface. Patented claims 1 and 9-12 recites a method administering a nanoparticle comprising a polynucleotide encapsulated in PBAE, surrounded by PGA, and comprising an antibody binding fragment exposed on the surface of the nanoparticle. Patented claim 17 recites a kit for practicing the method of claim 1 comprising the negatively charged polymer (i.e., PGA) covalently linked to the binding fragment of the antibody.
Regarding claims 103-104, 106, 111-112, it would have been obvious to one skilled in the art before the effective filing date of the claimed invention to have covalently linked the antibody binding fragment to the PGA in the composition claims. It would have amounted to the simple combination of claimed limitations. The skilled artisan would have predicted that the composition claims could comprise the PGA-antibody conjugate and been motivated to have done so because the patented kit claims recite such a conjugate for use in the patented method claims which also use nanoparticles comprising PBAE-capsulated nucleic acids surrounded by a PGA/antibody composite.
Regarding claims 105 and 109, Saltzman teaches delivering DNA-encoding gene editing agents such as TALENs in nanoparticles (Abstract). Saltzman teaches including functional molecules, such as PGA having 15-50 kDa ([0218]) and hematopoietic-cell targeting molecules ([0211]), to nanoparticles ([0207]). It would have been obvious to one skilled in the art to have modified the patented nanocarrier composition by specifically including polynucleotides that encoding TALENs and PGA that is 15 kDa. It would have amounted to the simple combination of known elements by known means to yield predictable results. The skilled artisan would have predicted that TALEN-encoding nucleic acid could be included in the patented composition and been motivated to have done so because Saltzman suggests that gene editing nucleases such as TALENs can be delivered to hematopoietic cells via functionalized nanoparticles. The skilled artisan would have been motivated to have specifically used 15 kDa PGA since Saltzman discloses that size for functionalized nanoparticles.
Regarding claims 108, Stephan teaches nanoparticles comprising polynucleotides and with lymphocyte-directing agents on the surface (Fig 2). Stephan teaches polynucleotides delivered by nanocarriers includes mRNA (embodiment 15). It would have been obvious to one skilled in the art to have modified the patented nanocarrier composition by specifically including mRNA as the nucleic acid. It would have amounted to the simple combination of known elements by known means to yield predictable results. The skilled artisan would have predicted that mRNA could be included in the patented composition and been motivated to have done so because there are only two options for polynucleotides that encode proteins – DNA and mRNA – and Stephan teaches mRNA delivery by lymphocyte-directed nanoparticles.
Regarding claim 110, Stasi teaches delivering CCR4-encoding polynucleotides to peripheral blood mononuclear cells (i.e., cells of hematopoietic origin) for the purpose of expressing CCR4 in T-lymphocytes (Abstract). Stasi teaches T-cells that express CCR4 have improved targeting/homing and antitumor activity (Abstract). It would have been obvious to one skilled in the art to have modified the patented nanocarrier composition by also including a polynucleotide encoding CCR4. It would have amounted to the simple combination of known elements by known means to yield predictable results. The skilled artisan would have predicted that CCR4-encoding polynucleotides could be included in the patented composition and been motivated to have done so because the patented claims also demonstrate that any polynucleotide can be included and Stasi teaches expressing CCR4 in T-cells increases their homing activity.
Claims 103-122 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of U.S. Patent No. 11872195.
Patented claim 1 recites a method comprising adding 12 kDa to 18 kDa polyglutamic acid (PGA) conjugated to selected cell targeting ligands that bind the selected cell population of hematopoietic origin to a first solution comprising nucleic acid encapsulated within poly(β-amino ester) (PBAE) to form a second solution, ii) incubating the second solution wherein selected cell-targeted synthetic nanocarriers form within 5 minutes of the adding and comprise A) the nucleic acid encapsulated within the PBAE; B) a coating comprising the PGA on the outer surface of the PBAE; and C) the selected cell targeting ligands extending from the outer surface of the coating and conjugated to the PGA within the coating. Patented claim 7 recites wherein the selected cell targeting ligands comprise a CD4 binding domain or a CD8 binding domain (i.e., an antibody). Therefore, patented claim 7 anticipates examined claims 103-106, 112-113, 116-117 and 122.
Patented claim 2 recites wherein the nucleic acid encodes a megaTAL as set forth in SEQ ID NO: 1 or comprises a sequence as set forth in SEQ ID NO: 37. Patented claim 3 recites wherein the nucleic acid is synthetic mRNA. Patented claim 5 recites wherein the nucleic acid encodes a phenotype-altering protein selected from FOXO1, LKB1, TCF7, EOMES, ID2, TERT, CCR2b, and CCR4. Patented claim 6 recites wherein the selected cell population of hematopoietic origin is selected from T cells, natural killer cells, monocytes, macrophages, dendritic cells, B cells, or hematopoietic stem cells.
Regarding claims 107-111 and 118-121, it would have been obvious to one skilled in the art before the effective filing date of the claimed invention to have combined the limitations of one or more of patented claims 2-3 and 5-6, into the method and composition of patented claim 7. It would have amounted to the simple combination of patented limitations by known means to yield predictable results. Because the limitations of patented claims 2-3 and 5-6 are merely the sequence of the polynucleotides, and it is clear from the patented claims that any polynucleotide can be encapsulated with the PBAE it would have been entirely predictable to have done so.
Regarding claims 114-115, it also would have been obvious to let the solutions incubate for 5 minutes at room temperature because (i) the patented claims recite that the nanoparticle components can self-assemble in 5 minutes and (ii) determining the temperature at which the components self-assemble is considered routine optimization of the patented method.
Claims 103-122 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of U.S. Patent No. 10188749.
Patented claim 1 recites A method of selectively modifying a selected cell population of hematopoietic origin comprising: (a) forming selected cell-targeted synthetic nanocarriers by (i) adding polyglutamic acid (PGA) conjugated to selected cell targeting ligands that bind the selected cell population of hematopoietic origin to a solution comprising nucleic acid encapsulated within a positively-charged carrier comprising poly(β-amino ester); and (ii) incubating the solution wherein selected cell-targeted synthetic nanocarriers form within 5 minutes of the adding and comprise (A) nucleic acid encapsulated within the positively-charged carrier comprising poly(β-amino ester); (B) a neutrally or negatively-charged coating comprising about a 15 kDa PGA on the outer surface of the positively-charged carrier; and (C) the selected cell targeting ligands extending from the outer surface of the neutrally or negatively-charged coating and conjugated to PGA within the neutrally or negatively-charged coating; and (b) administering the formed selected cell-targeted synthetic nanocarriers to a heterogenous mixture of ex vivo cells comprising the selected cell population of hematopoietic origin within a serum-free media thereby selectively modifying the selected cell population of hematopoietic origin. Patented claim 7 recites wherein the selected cell targeting ligand comprises a CD4 binding domain or a CD8 binding domain. Therefore, patented claim 7 anticipates examined claims 103-106, 112-113, 116-117 and 122.
Patented claim 2 recites wherein the nucleic acid encodes a megaTAL as set forth in SEQ ID NO: 1 or comprises a sequence as set forth in SEQ ID NO: 37. Patented claim 3 recites wherein the nucleic acid is synthetic mRNA. Patented claim 5 recites wherein the nucleic acid encodes a phenotype-altering protein selected from FOXO1, LKB1, TCF7, EOMES, ID2, TERT, CCR2b, and CCR4. Patented claim 6 recites wherein the selected cell population of hematopoietic origin is selected from T cells, natural killer cells, monocytes, macrophages, dendritic cells, B cells, or hematopoietic stem cells.
Regarding claims 107-111 and 118-121, it would have been obvious to one skilled in the art before the effective filing date of the claimed invention to have combined the limitations of one or more of patented claims 2-3 and 5-6, into the method and composition of patented claim 7. It would have amounted to the simple combination of patented limitations by known means to yield predictable results. Because the limitations of patented claims 2-3 and 5-6 are merely the sequence of the polynucleotides, and it is clear from the patented claims that any polynucleotide can be encapsulated with the PBAE it would have been entirely predictable to have done so.
Regarding claims 114-115, it also would have been obvious to let the solutions incubate for 5 minutes at room temperature because (i) the patented claims recite that the nanoparticle components can self-assemble in 5 minutes and (ii) determining the temperature at which the components self-assemble is considered routine optimization of the patented method.
Claims 103-106, 108, 111-112 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 148-153, 156-161, 173, 175-179 of copending Application No. 17044779. Claim 105 is rejected in view of Saltzman (US 20170283830 A1, priority to February 16, 2016).
Copending claim 148 recites injecting (i.e., administering) a first therapeutically effective amount of a nanoparticle to the subject wherein the nanoparticle results in expression of a chimeric antigen receptor (CAR) or a T cell receptor (TCR) selectively by T cells following the injecting…; wherein the nanoparticle comprises:(i) in vitro transcribed (IVT) mRNA encoding the CAR or TCR (i.e., a nucleic acid) encapsulated within a positively-charged polymer core; (ii) a neutral or negatively-charged polymer coating on the outer surface of the positively-charged core; and (iii) CD3, CD4 and/or COB single chain variable fragment (scFv) binding domains covalently linked to the neutral or negatively-charged polymer of the coating (i.e., an antibody-polymer conjugate). Copending claim 153 recites wherein the positively-charged polymer core comprises poly-(p-amino ester) (PBAE) and the negatively-charged coating comprises polyglutamic acid (PGA). Therefore, copending claim 153 anticipates examined claims 103-104, 106, 108, 111-112.
Regarding claim 105, Saltzman teaches delivering DNA in nanoparticles (Abstract). Saltzman teaches including functional molecules, such as PGA having 15-50 kDa ([0218]) and hematopoietic-cell targeting molecules ([0211]), to nanoparticles ([0207]). It would have been obvious to one skilled in the art to have modified the patented nanocarrier composition by specifically using PGA that is 15 kDa. It would have amounted to the simple combination of known elements by known means to yield predictable results. The skilled artisan would have been motivated to have specifically used 15 kDa PGA since Saltzman discloses that size for functionalized nanoparticles.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 103-106, 108, 111-112 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 148-153, 156-161, 173, 175-179 of copending Application No. 19559743. Claim 105 is rejected in view of Saltzman (US 20170283830 A1, priority to February 16, 2016).
Copending claim 1 recites injecting a first therapeutically effective amount of a nanoparticle to the subject wherein the nanoparticle results in expression of a chimeric antigen receptor (CAR) or a T cell receptor (TCR) selectively by T cells following the injecting…; wherein the first nanoparticle comprises: (i) in vitro transcribed (IVT) mRNA encoding the CAR or TCR encapsulated within a positively-charged polymer core; (ii) a neutral or negatively-charged polymer coating on the outer surface of the positively-charged core; and (iii) CD3, CD4 and/or CD8 single chain variable fragment (scFv) binding domains covalently linked to the neutral or negatively-charged polymer of the coating (i.e., an antibody-polymer conjugate) wherein the scFv binding domains extend from the surface of the coating thereby treating the subject in need thereof. Copending claim 6 recites wherein the positively-charged polymer core comprises poly-(β-amino ester) (PBAE) and the negatively-charged coating comprises polyglutamic acid (PGA). Therefore, copending claim 6 anticipates examined claims 103-104, 106, 108, 111-112.
Regarding claim 105, Saltzman teaches delivering DNA in nanoparticles (Abstract). Saltzman teaches including functional molecules, such as PGA having 15-50 kDa ([0218]) and hematopoietic-cell targeting molecules ([0211]), to nanoparticles ([0207]). It would have been obvious to one skilled in the art to have modified the patented nanocarrier composition by specifically using PGA that is 15 kDa. It would have amounted to the simple combination of known elements by known means to yield predictable results. The skilled artisan would have been motivated to have specifically used 15 kDa PGA since Saltzman discloses that size for functionalized nanoparticles.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims are allowable.
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/CATHERINE KONOPKA/Primary Examiner, Art Unit 1635
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