DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Election/Restrictions
Applicant's election with traverse of Group I, claims 12-26 and 36, in the reply filed on 9/19/2025 is acknowledged. The traversal is on the ground(s) that a search into prior art with regard to the invention of the different groups is so related that separate significant search efforts are unnecessary. The subject matter of each of the claim groups is linked by a common inventive concept, namely a Nipah virus envelope pseudotyped lentivirus particle comprising NiV-F lacking residues 525-546 of SEQ ID NO: 1, and NiV-G that is either wild type or has a deletion in its cytoplasmic tail, and which pseudotyped lentiviral particle has increased viral transduction titer compared to wild type counterparts. Accordingly, there is no serious search burden on the Examiner to collectively examine the different claim groups of the subject application. This is not found persuasive because, as discussed in the restriction requirement filed on 9/19/2025, there is a serious search burden, as demonstrated by the divergent subject matter, different classification, and requirement of a different field of search for the inventive groups.
The requirement is still deemed proper and is therefore made FINAL.
Claims 27-35 and 37-46 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 9/19/2025.
Claims 12-26 and 36 are under examination on the merits.
Information Disclosure Statement
The Information Disclosure Statements (IDSs) submitted on 5/16/2023 are in compliance with 37 CFR 1.97. Accordingly, the references cited in the IDSs are being considered by the examiner.
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Priority
This application is a CON of US Application 16/120,055 filed on 8/31/2018, now U.S. Patent No. 11576982, which is a CON of US Application 15/330,826 filed on 11/7/2016, now U.S. Patent No. 10,064,958, which is a CON of U.S. Application 14/387,371 filed on 9/23/2014, now U.S. Patent No. 9,486,539, which is a 35 U.S.C. 371 national stage filing of International Application No. PCT/US2013/032197 filed on March 15, 2013. Applicant’s claim for the benefit of prior-filed parent provisional application 61/734,580 filed on March 26, 2012, under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) is acknowledged.
Thus, the earliest possible priority date for the instant application is March 26, 2012.
Drawings
Color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
The patent or application file contains at least one drawing executed in color (Figs. 6 and 7). Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
Claim Objections
Claims 12 and 15 are objected to because of the following informalities: on lines 7-8, the claims recite “a cytoplasmic tail lacking amino residues 525-546”, rather than “a cytoplasmic tail lacking amino acid residues 525-546”. Appropriate 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.
Claim 25 is 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 25 recites the limitation "the nucleic acid effective for treating cancer" in line 2. There is insufficient antecedent basis for this limitation in the claim.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of pre-AIA 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) the invention was known or used by others in this country, or patented or described in a printed publication in this or a foreign country, before the invention thereof by the applicant for a patent.
Claims 12, 14, 22, and 24 are rejected under 35 U.S.C. 102(a) as being anticipated by Khetawat, et al. (Virol J. 2010 Nov 12;7:312. doi: 10.1186/1743-422X-7-312. PMID: 21073718; hereinafter referred to as “Khetawat”).
The claimed invention encompasses a method of delivering a nucleic acid to a cell, the method comprising contacting a Nipah virus (NiV) envelope pseudotyped lentivirus particle comprising a nucleic acid for delivery with cells, wherein the NiV pseudotyped lentivirus particle comprises Nipah Virus fusion (NiV-F) and Nipah Virus attachment (NiV-G) proteins, wherein the NiV-F protein comprises a deletion in its cytoplasmic tail relative to a wild type NiV-F sequence, wherein the NiV-F protein comprises a cytoplasmic tail lacking amino residues 525-546 of SEQ ID NO: 1, wherein the NiV-G protein is wild-type NiV-G or is a NiV-G protein that has a cytoplasmic tail truncation comprising a deletion in its cytoplasmic tail relative to wild-type NiV-G sequence, and wherein the NiV envelope pseudotyped lentivirus particle has increased viral transduction titer compared to a lentivirus particle pseudotyped with wild-type NiV-F and wild-type NiV-G (claim 12). In a specific embodiment, the contacting is in vitro (claim 13). In a different embodiment, the nucleic acid for delivery encodes a payload chosen from: a gene therapy payload, a payload that is toxic to the cell, or an ephrin antagonist (claim 22).
The Prior Art
Khetawat discloses a new and readily adaptable, reporter-gene containing, lentivirus-based pseudotyping system which utilizes functional F and G envelope glycoproteins of henipaviruses; NiV and HeV (p. 7, col. 2, last para.), falling within the scope of a Nipah virus envelope pseudotyped lentivirus particle comprising NiV-F and NiV-G glycoproteins. Khetawat also discloses that previous studies have demonstrated that efficient incorporation of heterologous envelope glycoproteins into HIV-1 or murine leukemia virus (MLV) particles often depended on the removal of part or all of the cytoplasmic tail domains from the pseudotyping glycoproteins (p. 5, col. 1). Khetawat generated a series of seven cytoplasmic tail truncation mutations in F glycoprotein, designated FΔCt1 to FΔCt7, by introducing stop codons into the coding sequence of the NiV F gene (Fig. 4; p. 5, cols. 1-2, bridging para.). These mutants included deletion of residues 518-546 of the C-terminus (Fig. 4). Additionally, Khetawat discloses that functional retrovirus particles pseudotyped with henipavirus F and G glycoproteins displayed proper target cell tropism and entry and infection was dependent on the presence of the HeV and NiV receptors ephrinB2 or B3 on target cells (Abstract). The pseudotyped lentiviruses pseudotyped with F and G envelope glycoproteins of NiV encoded either a luciferase or GFP reporter gene in the HIV-1 genome (p. 2, col. 2, para. 3). Khetawat further discloses that the henipaviruses bind and infect their host cells by a specific attachment step to the cell surface expressed proteins ephrin-B2 and -B3, and that upon receptor binding, the viral attachment glycoprotein triggers conformational changes in the F glycoprotein (p. 9, para. 2). Increased viral transduction is an inherent property of the pseudotyped lentivirus of Khetawat. See MPEP §2112.02(I)
Therefore, claims 12, 14, 22, and 24 are anticipated by Khetawat.
Claim Rejections - 35 USC § 103
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under pre-AIA 35 U.S.C. 103(a) are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
Claims 12-15, 22, 23-26, and 36 are rejected under 35 U.S.C. 103 as being unpatentable over Morizono (Nat Med. 2005 Mar;11(3):346-52. doi: 10.1038/nm1192. Epub 2005 Feb 13. PMID: 15711560; hereinafter referred to as “Morizono”) in view of Khetawat (supra).
The claimed invention encompasses a method of delivering a nucleic acid to a cell, the method comprising contacting a Nipah virus (NiV) envelope pseudotyped lentivirus particle comprising a nucleic acid for delivery with cells, wherein the NiV pseudotyped lentivirus particle comprises Nipah Virus fusion (NiV-F) and Nipah Virus attachment (NiV-G) proteins, wherein the NiV-F protein comprises a deletion in its cytoplasmic tail relative to a wild type NiV-F sequence, wherein the NiV-F protein comprises a cytoplasmic tail lacking amino residues 525-546 of SEQ ID NO: 1, wherein the NiV-G protein is wild-type NiV-G or is a NiV-G protein that has a cytoplasmic tail truncation comprising a deletion in its cytoplasmic tail relative to wild-type NiV-G sequence, and wherein the NiV envelope pseudotyped lentivirus particle has increased viral transduction titer compared to a lentivirus particle pseudotyped with wild-type NiV-F and wild-type NiV-G (claim 12). In specific embodiments, the contacting is in vitro (claim 13) or in vivo (claim 14). In a particular embodiment, the viral transduction titer is increased greater than 2-fold (claim 24).
The claimed invention also encompasses an embodiment where the method comprises administering a therapeutically effective amount of a NiV pseudotyped lentivirus particle comprising a nucleic acid for delivery to a subject (claim 15). In one embodiment, the administration of the NiV envelope pseudotyped lentivirus particle comprising the nucleic acid is effective for treating cancer (claim 25). Alternatively, the NiV envelope pseudotyped lentivirus particle is administered intravenously (claim 26).
In a specific embodiment, the contacting is in vivo (claim 14).
In a different embodiment, the nucleic acid for delivery encodes a payload chosen from: a gene therapy payload, a payload that is toxic to the cell, or an ephrin antagonist (claim 22). Another embodiment encompasses a method wherein the NiV-G comprises a single chain variable fragment (scFV) directed against a cell surface molecule other than ephrinB2 and/or B3 (claim 23).
Another embodiment of the claimed invention encompasses a method of administering a pharmaceutical composition comprising a Nipah virus (NiV) envelope pseudotyped lentivirus particle, wherein the NiV pseudotyped lentivirus particle comprises Nipah virus fusion (NiV-F) and Nipah virus attachment (NiV-G) proteins, wherein the NiV-F protein comprises a deletion in its cytoplasmic tail relative to a wildtype NiV-F sequence, wherein the NiV-F protein comprises a deletion in its cytoplasmic tail relative to a wild type NiV-F sequence, wherein the NiV-F protein comprises a cytoplasmic tail lacking amino acid residues 525-546 of SEQ ID NO: 1, wherein the NiV-G protein is wild-type NiV-G or is a NiV-G protein that has a cytoplasmic tail truncation comprising a deletion in its cytoplasmic tail relative to wild type NiV-G sequence, and wherein the NiV envelope pseudotyped lentivirus particle has increased viral transduction titer compared to a lentivirus particle pseudotyped with wild-type NiV-F and wild-type NiV-G, the method comprising systemically administering a therapeutically effective amount of the NiV pseudotyped lentivirus particle to a subject in need thereof (claim 36).
The Prior Art
Morizono discloses that targeted gene transduction to specific tissues and organs through intravenous injection would be the ultimate preferred method of gene delivery, and reports successful targeting in a living animal through intravenous injection of a lentiviral vector pseudotyped with a modified chimeric Sindbis virus envelope, which has a high titer and high targeting specificity, with low nonspecific infectivity in liver and spleen (Abstract, Figs. 1-3). Morizono specifically discloses oncoretroviral and lentiviral gene-targeting systems based on antibody-mediated specific binding of a modified chimeric Sindbis virus envelope (p. 346, col. 2, para. 2), which resulted in higher levels of infectivity in liver and spleen cells, which may be in part due to the high-affinity laminin receptor and heparin sulfate being among the known receptors of Sindbis virus, and the wide distribution of the receptors (p. 346, col. 2, para. 3). Morizono further discloses that in a mouse cancer model of metastatic melanoma, where human P-glycoprotein was ectopically expressed on the surface of melanoma cells and targeted by the pseudotyped lentivirus, an antibody specific for P-glycoprotein could be conjugated and successfully target metastatic melanoma cells (Abstract). The lentiviral vectors bore luciferase reporter genes, allowing for assessment of the location of infection in mice (p. 348, cols. 1-2, bridging para.). Morizono also discloses that future clinical application would probably be more effective with chimeric, recombinant, single-chain antibody sequences or specific ligand or peptide sequences (p. 350, col. 2, para 4). Morizono further discloses that pseudotyped virions successfully targeted metastatic melanoma cells growing in the lung after systemic administration by tail vein injection (Abstract). Morizono also states that inserting ligands, peptides or single-chain antibodies into the retroviral receptor binding envelope subunit has been the most common approach used to alter or restrict the host range of retroviral vectors (p. 346, col. 2, para. 1).
However, Morizono does not disclose a Nipah virus envelope pseudotyped lentiviral vector.
The teachings of Khetawat are described above.
It would have been obvious to one of ordinary skill in the art to modify the methods taught by Morizono to utilize the Niv-F and NiV-G pseudotyped lentivirus disclosed by Khetawat. Khetawat discloses lentiviral vectors pseudotyped with NiV F and G proteins and the ability of the NiV envelope proteins to confer fusion activity to the lentiviral particle. One of ordinary skill in the art would have been motivated to confer fusion activity to the lentiviral particle disclosed by Morizono to target metastatic melanoma or other specific tissues or cell types. There would be a reasonable expectation of success because Morizono discloses treatment with pseudotyped lentiviral particles and Khetawat teaches pseudotyping of lentiviral particles with NiV-G and NiV-F proteins.
Therefore, claims 12-15, 22-26, and 36 were prima facie obvious before the priority date of the instant invention.
Claim 20 is rejected under 35 U.S.C. 103 as being unpatentable over Morizono and Khetawat (supra), as applied to claims 12-15, 22-26, and 36 above, in further view of Aguilar et al. (J Virol. 2007 May;81(9):4520-32. doi: 10.1128/JVI.02205-06. Epub 2007 Feb 14. PMID: 17301148; hereinafter referred to as “Aguilar”).
In another embodiment, the NiV-F protein or NiV-G protein further comprises a hyperfusogenic mutation (claim 20).
The Prior Art
The teachings of Morizono and Khetawat are described above. However, they do not disclose a NiV-F protein or NiV-G protein that further comprises a hyperfusogenic mutation.
Aguilar discloses a tribasic KKR motif in the membrane adjacent region of NiV-F that is important for modulating cell-cell fusion, wherein K1A mutation increased fusion 5.5-fold (Abstract; Fig. 1; Table 1). Aguilar discloses that its results suggest that the hyperfusogenicity phenotype of K1A is governed by the rate of 6HB formation during fusion pore formation, resulting in increased fusion kinetics (Fig 6; p. 4529, col. 2, para. 2).
It would have been obvious to one of ordinary skill in the art to modify the methods taught by Morizono to utilize the NiV-F and NiV-G pseudotyped lentivirus disclosed by Khetawat bearing a K1A mutation in NiV-F that is hyperfusogenic. Aguilar discloses that K1A mutation increases fusion 5-5fold relative to wild-type NiV-F, resulting in increased fusion kinetics. One of ordinary skill in the art would have been motivated to make a more fusogenic pseudotyped lentivirus. There would be a reasonable expectation of success because Morizono and Khetawat demonstrate use of pseudotyped lentiviral particles, even NiV-F and NiV-G pseudotyped lentiviral particles in the case of Khetawat, and Aguilar demonstrates the single K1A mutation in NiV-F confers the hyperfusogenic phenotype.
Therefore, claim 20 was prima facie obvious before the priority date of the instant invention.
Claim 20 is rejected under 35 U.S.C. 103 as being unpatentable over Khetawat (supra), as applied to claims 12, 14, 22, and 24 above, in further view of Aguilar et al. (supra).
In another embodiment, the NiV-F protein or NiV-G protein further comprises a hyperfusogenic mutation (claim 20).
The Prior Art
The teachings of Khetawat are described above. However, they do not disclose a NiV-F protein or NiV-G protein that further comprises a hyperfusogenic mutation.
Aguilar discloses a tribasic KKR motif in the membrane adjacent region of NiV-F that is important for modulating cell-cell fusion, wherein K1A mutation increased fusion 5.5-fold (Abstract; Fig. 1; Table 1). Aguilar discloses that its results suggest that the hyperfusogenicity phenotype of K1A is governed by the rate of 6HB formation during fusion pore formation, resulting in increased fusion kinetics (Fig 6; p. 4529, col. 2, para. 2).
It would have been obvious to one of ordinary skill in the art to modify the methods and compositions taught by Khetawat to utilize the NiV-F and NiV-G pseudotyped lentivirus disclosed by Khetawat bearing a K1A mutation in NiV-F that is hyperfusogenic. Aguilar discloses that K1A mutation increases fusion 5.5-fold relative to wild-type NiV-F, resulting in increased fusion kinetics. One of ordinary skill in the art would have been motivated to make a more fusogenic pseudotyped lentivirus. There would be a reasonable expectation of success because Khetawat demonstrates use NiV-F and NiV-G pseudotyped lentiviral particles, and Aguilar demonstrates the single K1A mutation in NiV-F confers the hyperfusogenic phenotype.
Therefore, claim 20 was prima facie obvious before the priority date of the instant invention.
Claim 21 is rejected under 35 U.S.C. 103 as being unpatentable over Morizono and Khetawat (supra), as applied to claims 12-15, 22-26, and 36 above, in further view of Xu et al. (Proc Natl Acad Sci U S A. 2008 Jul 22;105(29):9953-8. doi: 10.1073/pnas.0804797105. Epub 2008 Jul 16. PMID: 18632560; hereinafter referred to as “Xu”).
Alternatively, the NiV-G protein further comprises a mutation that abrogates ephrinB2 and B3 binding (claim 21).
The Prior Art
The teachings of Morizono and Khetawat are described above. Morizono further describes ablating residual infectivity by targeting domains reported to affect binding to target cells (p. 348, col. 1, para. 1). However, they do not disclose a the NiV-G protein further comprising a mutation that abrogates ephrinB2 and B3 binding.
Xu discloses that henipavirus G glycoproteins engage the highly conserved ephrin-B2 and ephrin-B3 cell surface proteins as their entry receptors (Abstract), resolves the crystal structure of NiV-G alone or bound to ephrin-B3 (Figs 1-3), and identifies several NiV-G residues critical for ephrin-B3 binding (Fig. 5). NiV-G E501, E533, and R242 form salt bridges with ephrin-B3 (Fig. 5a), and an intricate hydrogen bond network further stabilized the NiV-G/ephrin complex (p. 9955, col. 1, para. 1).
It would have been obvious to one of ordinary skill in the art to modify the methods taught by Morizono to utilize the NiV-F and NiV-G pseudotyped lentivirus disclosed by Khetawat, with one or more residues critical for NiV-G binding ephrin (identified in Xu) mutated to abrogate NiV-G’s ephrin binding capacity. Morizono describes ablating residual infectivity by targeting domains reported to affect binding to target cells (p. 348, col. 1, para. 1). One of ordinary skill in the art would have been motivated to ablate residual infectivity of target cells, as described by Morizono.
Therefore, claim 21 was prima facie obvious before the priority date of the instant invention.
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 12-15, 20, 22, 24-26 and 36 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 of U.S. Patent No. 9486539 B2 in view of Khetawat, Morizono, Aguilar, and Xu (supra). Although the claims at issue are not identical, they are not patentably distinct from each other. Each set of claims involves a Nipah virus envelope pseudotyped lentivirus particle comprising NiV-F and NiV-G proteins, wherein the NiV-F glycoprotein has a cytoplasmic tail truncation (instant claims 12 & 15, ‘539 claims 1 and 3). Although 539’s claims require “deletion of amino acid residues 525-544 of SEQ ID NO: 1” (‘539 claims 1 and 3), whereas the instant claims require “the NiV-F protein comprises a cytoplasmic tail lacking amino acid residues 525-546 of SEQ ID NO: 1”, in view of Khetawat teaching deletion of residues 518-546 of NiV-F, the instant claims’ deletion of amino acid residues 525-546 of NiV-F is obvious. Notably, ‘539 does not specifically encompass a deletion of at least 30 contiguous amino acids from NiV-G, however, it does disclose a number of truncated NiV-G mutants with deletion of contiguous amino acids (‘539 claim 3).
Not all of the claimed limitations of the instant claims are contemplated by ‘539, such as contacting a cell with the lentiviral vector in vivo (instant claim 14), a hyperfusogenic mutation to NiV-F or NiV-G (instant claim 20), the NiV-G protein further comprising a mutation that abrogates ephrinB2 and B3 binding (instant claim 21), the nucleic acid for delivery encodes a payload chosen from: a gene therapy payload, a payload that is toxic to the cell, or an ephrin antagonist (instant claim 22), the NiV-G comprises a single chain variable fragment (scFv) directed against a cell surface molecule other than ephrinB2 and/or B3 (instant claim 23), the administration of the NiV envelope lentivirus particle comprising the nucleic acid is effective for treating cancer (instant claim 25), or the NiV envelope pseudotyped lentivirus particle is administered intravenously (instantly claim 26); however, they would be obvious in view of Khetawat, Morizono, Aguilar, and Xu.
The teachings of Khetawat, Morizono, Aguilar, and Xu are described in detail above in rejections under 35 U.S.C. §§102 & 103.
The instant claims would have been obvious to one of ordinary skill in the art, based on ‘539 in view of the teachings of Khetawat, Morizono, Aguilar, and Xu. Therefore, Claims 12-15, 20, 22, 24-26 and 36 were prima facie obvious to one of ordinary skill in the art based on ‘539 in view of the teachings of Khetawat, Morizono, Aguilar, and Xu.
Claims 12-15, 20, 22, 24-26 and 36 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No. 10064958 B2 in view of Khetawat, Morizono, Aguilar, and Xu (supra). Although the claims at issue are not identical, they are not patentably distinct from each other. Each set of claims involves methods of delivering a Nipah virus envelope pseudotyped lentivirus particle comprising NiV-F and NiV-G proteins, wherein the NiV-F glycoprotein has a cytoplasmic tail truncation (i.e., instant claims 12, 15, & 36, ‘958 claims 1, 5, 7, and 17). Although 958’s claims say “deletion of amino acid residues 525-544 of SEQ ID NO: 1” (‘958 claims 1, 5, 7, and 17), in view of Khetawat teaching deletion of residues 518-546 of NiV-F, the instant claims’ deletion of amino acid residues 525-546 of NiV-F is obvious.
Not all of the claimed limitations are contemplated by the instant claims are specifically contemplated by ‘958, such as a hyperfusogenic mutation to NiV-F or NiV-G (instant claim 20), the NiV-G protein further comprising a mutation that abrogates ephrinB2 and B3 binding (instant claim 21), the nucleic acid for delivery encodes a payload chosen from: a gene therapy payload, a payload that is toxic to the cell, or an ephrin antagonist (instant claim 22), or the NiV-G comprises a single chain variable fragment (scFv) directed against a cell surface molecule other than ephrinB2 and/or B3 (instant claim 23); however, they would be obvious in view of Khetawat, Morizono, Aguilar, and Xu.
The teachings of Khetawat, Morizono, Aguilar, and Xu are described in detail above in rejections under 35 U.S.C. §§102 & 103.
The instant claims would have been obvious to one of ordinary skill in the art, based on ‘958 in view of the teachings of Khetawat, Morizono, Aguilar, and Xu. Therefore, Claims 12-15, 20, 22, 24-26 and 36 were prima facie obvious to one of ordinary skill in the art based on ‘958 in view of the teachings of Khetawat, Morizono, Aguilar, and Xu.
Claims 12-20, 22, 24-26 and 36 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No. 11576982 B2 in view of Khetawat (supra). Although the claims at issue are not identical, they are not patentably distinct from each other. Further, each set of claims encompasses a NiV envelope pseudotyped lentivirus particle comprising NiV-F and NiV-G, which can be truncated with a deletion of amino acid residues 525-546 of SEQ ID NO: 1 of the cytoplasmic tail of NiV-F (instant claim 12, ‘982 claim 1), and the NiV-G protein comprises a deletion of at least 10, 15, 20, or 30 contiguous amino acid residues from the cytoplasmic tail (instant claims 16-19, ‘982 claims 3-6). Additionally, the pseudotyped lentivirus particle exhibits a transduction titer at least 2-fold higher compared to a NiV envelope pseudotyped lentivirus particle with wild-type NiV-F and NiV-G (instant claims 12 and 24, ‘982 claims 1 and 2). Each of set claims encompasses the NiV-F protein or NiV-G protein comprising a hyperfusogenic mutation, (instant claim 20, ‘982 claim 8), or the NiV-G protein further comprises a mutation that abrogates ephrinB2 and B3 binding (instant claim 21, ‘982 claim 9). Additionally, each set of claims encompasses the pseudotyped lentivirus particle comprising a nucleic acid encoding a payload chosen from: a gene therapy payload, a payload that is toxic to a cell, or an ephrin antagonist (instant claim 22, ‘982 claim 12). Alternatively, each set of claims includes the NiV-G comprising a single chain variable fragment (scFV) directed against a cell surface molecule other than ephrinB2 and/or B3 (instant claim 23, ‘982 claims 13-14).
The instant and ‘982 claims differ in that the instant claims are a method of use, whereas ‘982 claims are drawn to a Nipah virus envelope pseudotyped lentivirus particle, the patented invention still renders obvious the instant invention because ‘982 suggests viral transduction and “for delivery to a cell” (i.e.,‘982 claims 1-2 and 15-17).
Therefore, Claims 12-20, 22, 24-26 and 36 were prima facie obvious to one of ordinary skill in the art based on ‘982 in view of the teachings of Khetawat.
Conclusion
No claim is allowed.
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/JEFFREY MARK SIFFORD/Examiner, Art Unit 1671
/BENJAMIN P BLUMEL/Primary Examiner, Art Unit 1671