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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on Dec. 02, 2025.
DETAILED ACTION
Acknowledgement is hereby made of receipt and entry of the communication filed on Dec. 02, 2025. Claims 1, 3-7, 9-14, 17-18, 20-26, 28 and 30 are pending and are currently examined.
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.
(Previous rejection- withdrawn) Claims 11, 18 and 26 were rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point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.
This rejection is withdrawn in view of the amendment filed on Dec. 02, 2025.
Claim Rejections - 35 USC § 112 (Written Description)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
(New rejection) Claims 1, 3-7, 9-14, 17-18, 20-26, 28 and 30 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The amended base claims 1 and 14, and the claims 3-7 and 9 are directed to a lentiviral vector system/particle comprising a plasmid, wherein one of the nucleic acid sequences comprised in the plasmid encodes the woodchuck hepatitis virus post-transcriptional regulatory element (WPRE) that comprises the sequence of SEQ ID NO: 1, or a variant thereof, at least a portion of the 5' long terminal repeat comprises at least one of SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5 and/or SEQ ID NO:6, or a variant thereof, at least a portion of the 3' terminal repeat comprises at least one of SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6 and/or SEQ ID NO:7, or a variant thereof, an encapsidation element comprises SEQ ID NO: 10 and/or SEQ ID NO: 13, or a variant thereof, the nucleic acid sequence encoding an RRE comprises SEQ ID NO: 14, or a variant thereof and the nucleic acid sequence encoding a gag polyprotein and a gag-pol polyprotein comprises SEQ ID NO:24, or a variant thereof.
The written description rejection is made because the claims are interpreted as drawn to a variant of SEQ ID NO: 1, SEQ ID NOs: 3-7, SEQ ID NOs: 10 and 13-14, and SEQ ID NO: 24, which are not necessary represented as the claimed molecule WPRE, promoter, LTRs, encapsidation element, RRE and gag and gag-pol.
To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116. However, a showing of possession alone does not cure the lack of a written description. Enzo Biochem, Inc. v. Gen-Probe, Inc., 323 F.3d 956, 969-70, 63 USPQ2d 1609, 1617 (Fed. Cir. 2002). For example, it is now well accepted that a satisfactory description may be found in originally-filed claims or any other portion of the originally-filed specification. See In re Koller, 613 F.2d 819, 204 USPQ 702 (CCPA 1980); In re Gardner, 475 F.2d 1389, 177 USPQ 396 (CCPA 1973); In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976). However, that does not mean that all originally-filed claims have adequate written support. The specification must still be examined to assess whether an originally-filed claim has adequate support in the written disclosure and/or the drawings. See MPEP 2163. I.
In Regents of the University of California v. Eli Lilly and Co. 119 F.3d 1559, 43 USPQ2d 1398 (Fed. Cir. 1997), the Court decided that adequate written description of genetic material "requires a precise definition, such as by structure, formula, chemical name, or physical properties, not a mere wish or plan for obtaining the claimed chemical invention." Id. 43 USPQ2d at 1404 (quoting Fiefs, 984 F.2d at 1171, 25 USPQ2d at 1606). In AbbVie Deutschland GMBH & Co. v. Janssen Biotech, Inc. (Court of Appeals, Federal Circuit 2014), the Court ruled that “[W]ith the written description of a genus, however, merely drawing a fence around a perceived genus is not a description of the genus. One needs to show that one has truly invented the genus, i.e., that one has conceived and described sufficient representative species encompassing the breadth of the genus. Otherwise, one has only a research plan, leaving it to others to explore the unknown contours of the claimed genus. See Ariad, 598 F.3d at 1353 (The written description requirement guards against claims that “merely recite a description of the problem to be solved while claiming all solutions to it and . . . cover any compound later actually invented and determined to fall within the claim' s functional boundaries.”).”
The instant specification discloses the definition of the “variant” as “By "variant" of a sequence, we include insertions, deletions and substitutions, either conservative or non-conservative. In particular, we include variants of the nucleotide sequence where such changes do not substantially alter the biological activity of the nucleic acid sequence or of the product encoded by the nucleic acid sequence. A skilled person would know that such sequences can be altered without the loss of biological activity… Moreover, small deletions within non-functional regions of the protein can also be tolerated and hence are considered "variants" for the purpose of the present invention. The experimental procedures described herein can be readily adopted by the skilled person to determine whether a "variant" can still function” (See the instant specification [0092]). However, the variant of SEQ ID NO: 1 can also be a different gene/protein or. For example, the SEQ ID NO: 11 of Xiao et al. (US 11,566,223 B2, patented on Jan, 31, 2023, Filed on May 30, 2018) shares 99.7% identical to the claimed SEQ ID NO: 1, where the SEQ ID NO: 11 encodes CD20 CAR (See Xiao et al., Table 1, column 51-52; Table A below) nut not the WPRE.
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Therefore, the specification does not provide evidence to support if the variant of WPRE, variant promoter, variant LTRs, variant encapsidation element, variant RRE and variant gag and gag-pol are the same or can function the same as unmodified WPRE, promoter, LTRs, encapsidation element, RRE and gag and gag-pol plays as claimed.
The court clearly states in Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, that "applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the 'written description' inquiry, whatever is now claimed." (See page 1117).
As discussed above, the skilled artisan cannot envision the detailed components of the claims. Therefore, the full breadth of the claims does not meet the written description provision of 35 U.S.C. 112, first paragraph.
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.
(Previous rejection- withdrawn) Claims 1, 14, 17, 18, 20-24 and 30 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Charneau et al. (EP2385107 A1, date of filing, Mar. 05, 2010) as evidenced by USDA-CFSPH-2015.
This rejection is withdrawn in view of the amendment file on Dec. 02, 2025.
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.
(New Rejection-necessitated by amendment) Claims 1, 10-11, 14, 17, 18, 20-24, 26 and 30 are rejected under 35 U.S.C. 103 as being unpatentable over Charneau et al. (EP2385107 A1, date of filing, Mar. 05, 2010) as evidenced by USDA-CFSPH-2015 and in view of Girones et al. (Proc Natl Acad Sci U S A. 1989 Mar;86(6):1846-9).
The amended base claim 1 is directed to a lentiviral vector system comprising a plasmid, wherein the plasmid comprises a nucleic acid sequence encoding a promoter, a nucleic acid sequence encoding an encapsidation element, a nucleic acid sequence encoding a rev-responsive element (RRE), a site for the insertion of a nucleic acid for transfer, a woodchuck hepatitis virus post- transcriptional regulatory element (WPRE), and at least a portion of a 5' terminal repeat and at least a portion of a 3' terminal repeat;
wherein the nucleic acid sequence encoding an encapsidation element and the nucleic acid sequence encoding at least a portion of a 5' terminal repeat and at least a portion of a 3' terminal repeat are small ruminant lentivirus nucleic acid sequences;
wherein the lentiviral vector system further comprises a packaging plasmid comprising a nucleic acid sequence encoding a gag polyprotein and a gag-pol polyprotein; and
wherein the WPRE comprises the sequence of SEQ ID NO: 1, or a variant thereof.
Base claim 14 is directed to a lentiviral vector particle derived from a small ruminant lentivirus, wherein the lentiviral vector particle comprises a nucleic acid sequence encoding an encapsidation element, a nucleic acid sequence encoding a rev-responsive element (RRE), a nucleic acid sequence for transfer, a woodchuck hepatitis virus post-transcriptional regulatory element (WPRE), and at least a portion of a 5' terminal repeat and at least a portion of a 3' terminal repeat;
wherein the nucleic acid sequence encoding an encapsidation element and the nucleic acid sequence encoding at least a portion of a 5' terminal repeat and at least a portion of a 3' terminal repeat are small ruminant lentivirus nucleic acid sequences, and
wherein the WPRE comprises the sequence of SEQ ID NO: 1, or a variant thereof.
Charneau et al. teaches that the "vector genome" of the lentiviral vector particles is a recombinant vector which also comprises the polynucleotide or transgene of interest encoding the polypeptide(s) of malaria parasite. The lentiviral-based sequence and polynucleotide/transgene of the vector genome are borne by a plasmid vector thus giving rise to the "transfer vector" also referred to as "sequence vector” (See [0021]). Charneau et al. discloses that the plasmid/transfer vector comprises a promoter, an encapsidation element, Rev-responsive element (RRE), WPRE, 5’-LTR and 3’ LTR (See [0090] to [0094]), where the encapsidation element is the region of psi (Ψ) in the vector genome [See [0092]-[0094]) and the original 5’ LTR and 3’ LTR sequences of the lentivirus are used in the vector genome, but the 3’-LTR at least is modified with respect to the 3’LTR of the original lentivirus at least in the U3 region which for example can be deleted or partially deleted for the enhancer. The 5’LTR may also be modified, especially in its promoter region where for example a Tat-independent promoter may be substituted for the U3 endogenous promoter (See [0078]). Also, Charneau et al. teaches that the lentiviral vector particles are the product recovered from co-transfection of mammalian cells with a vector plasmid and an encapsidation plasmid comprising lentiviral gag-pol packaging sequences suitable for the production of integration-competent vector particles (See e.g.[0066]), and discloses that in order to obtain lentiviral vectors according to the invention, the vector genome (as a vector plasmid) must be encapsidated in particles or pseudo-particles. Accordingly, lentiviral proteins, except the envelope proteins, have to be provided in trans to the vector genome in the producing system together with the vector genome having recourse to at least one encapsidation plasmid carrying the gag gene (See [0097]). Charneau et al. also teaches that the promoters may also be used in regulatory expression sequences involved in the expression of gag-pol derived proteins from the encapsidation plasmids (See [0060]), which teaches a plasmid in the lentiviral vector system contains gag protein and gag-pol protein. Charneau et al. also teaches that the lentiviral vector providing the necessary sequences for the vector genome can be originating from lentiviruses such as HIV, EIAV, CAEV, VISNA, FIV, BIV, SIV, HIV-2, HIV-O which are capable of transfecting human cells (See e.g.[0075]), which teaches that the viral vector system is from a lentivirus. Because the CAEV and VISNA belong to the small ruminant lentivirus, the lentiviral vector system used in Charneau can be the small ruminant lentivirus if CAEV and VISNA are selected to be used (claim 14). The evidence of CAEV and VISNA belonging to the small ruminant lentivirus can be demonstrated by the USDA-CFSPH-2015. USDA teaches that Small ruminant lentivirus (SRLVs) belong to the genus Lentivirus in the family Retroviridae (subfamily Orthoretrovirinae). Two of these viruses have been known for many years: maedi-visna virus (MVV), which mainly causes the diseases maedi and visna in sheep, and caprine arthritis encephalitis virus (CAEV), which primarily causes arthritis and encephalitis in goats (See page 1, paragraph 2).
Accordingly, Charneau et al. teaches a lentiviral vector system, which includes a plasmid comprising the nucleic acid sequence encoding the promoter, encapsidation element, RRE, WPRE and both 5’- and 3’-LTR. Also, Charneau et al. teaches an encapsidation plasmid encoding a gag polyprotein and a gag-pol polyprotein, where the nucleic acid sequence can be the small ruminant lentivirus nucleic acid sequences such as CAEV and VISNA.
As for the amended phrase “a lentiviral vector system”, although Charneau et al. does not specifically use the exact phrase, Charneau et al. teaches a lentiviral vector particle that comprises the same elements as claimed, therefore, the lentiviral vector particles of Charneau teaches a lentiviral vector system/lentiviral vector particles as claimed in the base claims 1 and 14.
As for the limitation “wherein the WPRE comprises the sequence of SEQ ID NO: 1, or a variant thereof” amended in the base claims 1 and 14, SEQ ID NO: 1 is free of art, however, a variant of SEQ ID NO: 1 is taught by Girones’s study. Girones et al. completes nucleotide sequence of a molecular clone of woodchuck hepatitis virus that is infectious in the natural host and demonstrates that this genome is infectious when transfected directly into the livers of susceptible woodchucks. This recombinant should prove useful in attempts to understand hepadnavirus replication and gene expression (See Abstract; page 1849, left column, paragraph 2). The sequence reported in their paper is being deposited in the EMBL/GenBank data base (accession no. J04514; https://www.ncbi.nlm.nih.gov/nuccore/J04514). The sequence of J04514 shares 99.7% identity with the claimed SEQ ID NO: 1, where the J04514 has two nucleotides missed (595bp -596bp) less than SEQ ID NO: 1. The sequence comparison is shown in Table B below.
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It would have been prima facie obvious for one having ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Charneau and Girones to arrive at an invention as claimed. One of skill in the art would have been motivated to use known WPRE variants of SEQ ID NO: 1, including the WPRE variant of Girones, to use in the construct of Charneau and construct a lentiviral vector system and/or lentiviral vector particle as claimed (See MPEP 2144.06: Substituting equivalents known for the same purpose). There would be a reasonable expectation of success to construct such a lentiviral vector system/particle comprising the variant of SEQ ID NO: 1 as claimed based on the techniques taught by Charneau and Girones.
Thus, the invention as a whole was clearly prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Regarding claims 10 and 11, they require a lentiviral vector system according to claim 8 further comprising an additional plasmid comprising a nucleic acid sequence encoding an envelope protein, where the envelope protein is derived from a vesicular stomatitis virus (VSG).
Charneau et al. teaches that the lentiviral vector particles are the product recovered from a stable cell line with a VSV-G envelope expression plasmid comprising a polynucleotide encoding a VSV-G envelope protein or envelope protein, wherein said polynucleotide is under the control of regulating expression sequences, in particular regulatory expression sequences comprising an inducible promoter (See e.g. [0067]).
Regarding claim 17, it requires that a method of transducing a cell, said method comprising contacting a cell to be transduced with a lentiviral vector particle derived from a small ruminant lentivirus according to claim 14.
Charneau et al. teaches that the plasmid containing this construct is used for transfection or for transduction of cells suitable for the preparation of particles (See [0059]).
Regarding claim 18, it requires a method of raising an immune response in an animal, said method comprising administering an immunogenic amount of a lentiviral vector particle derived from a small ruminant lentivirus according to claim 14 to an animal.
Charneau et al. teaches that the lentiviral vector particles, compositions comprising the same or the combination of compounds of the invention, when administered to a host in needs thereof, especially to a mammalian in particular to a human host, elicit an immune response (See [0152]). Charneau et al. also teaches that the lentiviral vector particles or the combination of compounds of the invention is especially used in a particular embodiment for the prophylactic immunization against malaria parasite infection or against parasite-induced pathology in mammalian, host, especially in a human host (See [0161]).
Regarding claim 20, it is directed to an immunogenic composition or vaccine comprising the lentiviral vector particle according to claim 14.
Charneau et al. teaches that their invention provides a novel lentiviral-based vector, as a new platform for the preparation or development of malaria vaccine (See [0012]), and also teaches that in a particular embodiment of the invention, a composition of lentiviral vector particles is prepared wherein said lentiviral vector particles are formulated with a suitable administration vehicle for use for prophylactic immunization against malaria parasite infection or against parasite-induced pathology in a mammalian host, especially in a human host (See [0154]).
Regarding claims 21 and 22, they require the immunogenic composition or vaccine further comprises pharmaceutically acceptable and/or sterile excipients, carriers and/or diluents, and further comprises or is admixed with an antigen, a polypeptide and/or an adjuvant respectively.
Charneau et al. teaches that the lentiviral vector particles or the combination of compounds may be used in association with an adjuvant compound suitable for administration to a mammalian, especially a human host, and/or with an immunostimulant compound, together with an appropriate delivery vehicle (See [0170]). Charneau et al. teaches a composition of lentiviral vector particles is prepared wherein said lentiviral vector particles are formulated with a suitable administration vehicle for use for prophylactic immunization against malaria parasite infection or against parasite-induced pathology in a mammalian host, especially in a human host (See [0154]).
Regarding claim 23, it requires that the site for the insertion of the nucleic acid for transfer is adjacent to the WPRE.
Charneau et al. teaches claim 23 by the following construct such as plasmid pTRIP-ΔU3-CMV-Hep17 CO-WPRE (See [0185]; Figure 13 of the Restriction map, page 146 and below). The map shows that the codon optimized (CO, see [0038]) Hep 17 (hepatocyte erythrocyte protein, see [0030]) gene is inserted next to WPRE.
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Regarding claim 24, it requires that at least a portion of the 5' long terminal repeat is between the nucleic acid sequence encoding a promoter and the site for the insertion of a nucleic acid for transfer.
Charneau et al. teaches that a codon optimized transfer gene such as circumsporozoite protein (CSP), Hep17 and merozoite surface protein-1 (MSP1) is inserted downstream of the 5’ LTR (See e.g.[0043], Figures 11 to 16, pages 145-147), and the 5’ LTR has the internal U3 promoter region upstream (See Figures 11-16, pages 145-147), where the U3 region of the LTR 5’ can be replaced by a non-lentiviral U3 or by a promoter suitable to drive tat-independent primary transcription (See [0091]).
Regarding claim 26, Charneau et al. teaches that the invention relates to lentiviral vector particles pseudotyped with a determined heterologous viral envelope protein or viral envelope protein originating from an RNA virus and which comprise in its genome at least one recombinant polynucleotide encoding at least one polypeptide(s) carrying epitope(s) of an antigen of a Plasmodium parasite capable of infecting a mammalian host. The lentiviral vector particles are used in order to elicit an immunological response against malaria parasites (See Abstract), which indicates the vector system further contain a therapeutic gene. Charneau et al. also teaches that in a particular embodiment, the DNA flap is inserted upstream of the polynucleotide encoding the polypeptide of a malaria antigen (See [0080]), and codon optimization can improve the efficiency of the transfer of the polynucleotide encoding the polypeptide of an antigen of the malaria parasite (transgene) in the genome of the transduced cells of the host (See [101]). Here the descriptions indicate the lentiviral vector system further comprises a nucleic acid for transfer at said site for insertion.
Regarding claim 30, Charneau et al. teaches that their invention provides a novel lentiviral-based vector, as a new platform for the preparation or development of malaria vaccine for human application (See e.g. [0012]).
(New rejection) Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over Charneau et al. (EP2385107 A1, date of filing, Mar. 05, 2010) as evidenced by USDA-CFSPH-2015 and in view of Girones et al. (Proc Natl Acad Sci U S A. 1989 Mar;86(6):1846-9) as applied on claims 1, 10-11, 14, 17, 18, 20-24, 26 and 30 above, and in view of Raney et al. (US 2006/0246421 A1, publication date: Nov. 2, 2006).
Claim 3 is directed to the nucleic acid sequence encoding a promoter comprises SEQ ID NO: 2, or a variant thereof.
Relevance of Chaeneau et al. is set forth above, However, it is silent on a promoter comprises SEQ ID NO: 2, or a variant.
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Raney et al. describes compounds and methods for inhibiting hepatitis c virus replication and teaches that the adenoviral vectors are produced using commercially available methods and materials, including the pAdEasy-1 vector system from Stratagene (La Jolla, Calif.) (64, 65). The D290A NS3 DNA is cloned behind the cauliflower mosaic virus (CMV) promoter in pShuttle-CMV (64) (SEQ ID NO:5) in E. coli. The CMV promoter is nucleotides 345-932 of SEQ ID NO:5 (See 0234), where the SEQ ID NO: 5 shares 98.8% identify with the claimed SEQ ID NO: 2 (See Table C below), which can be considered as a “variant thereof”.
It would have been prima facie obvious for one having ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Charneau and Raney to arrive at an invention as claimed. One of skill in the art would have been motivated to use known promoters, including the promoter of Raney, to substitute for the promoter of Charneau and construct a lentiviral vector system as claimed (See MPEP 2144.06: Substituting equivalents known for the same purpose). There would be a reasonable expectation of success to construct such a lentiviral vector system/particle comprising the variant of SEQ ID NO: 1 as claimed based on the techniques taught by Charneau and Raney.
(New Rejection-necessitated by amendment) Claims 4-5 are rejected under 35 U.S.C. 103 as being unpatentable over Charneau et al. (EP2385107 A1, date of filing, Mar. 05, 2010) as evidenced by USDA-CFSPH-2015 and in view of Girones et al. (Proc Natl Acad Sci U S A. 1989 Mar;86(6):1846-9) as applied on claims 1, 10-11, 14, 17, 18, 20-24, 26 and 30 above, and in view of GenBank: L06906.1 of Visna/Maedi virus strain kv1772, complete genome.
Claims 4-5 are directed to at least a portion of the 5' long terminal repeat comprises at least one of SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5 and/or SEQ ID NO:6, or a variant, and at least a portion of the 3' terminal repeat comprises at least one of SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6 and/or SEQ ID NO:7, or a variant, respectively.
Relevance of Chaeneau et al. is set forth above. However, it is silent on the both 5’ LTR and 3’ LTR comprise at least one of SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO: 6 and SEQ ID NO: 7.
The Visna/Maedi virus strain kv1772, complete genome, is referred as GenBank: L06906.1. After sequence analysis, GenBank: L06906.1. contains the full-length of the SEQ ID NO: 4 as claimed within the regions at 8852 bp to 9105 bp (See Table 3, below). Based on the sequence features, the repeat_ region of 8852…9105 is the long terminal repeat (LTR) sequences.
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It would have been prima facie obvious for one having ordinary skill in the art before the effective filing date of the claimed invention to select a LTR known in the art such as GenBank: L06906.1 as the LTR sequences of Charneau, which contains the SEQ ID NO: 4 as claimed. One of skill in the art would have been motivated to use the known Visna LTR sequence of GenBank: L06906.1 as the nucleic acid sequence to encode such as RRE, WPRE and LTR, and there would be a reasonable expectation of success to construct a lentiviral vector system comprise the nucleic acid sequence encoding an SEQ ID NO: 4 of the small ruminant lentivirus nucleic acid sequences as claimed.
(New Rejection-necessitated by amendment) Claims 6-7 and 12-13 are rejected under 35 U.S.C. 103 as being unpatentable over Charneau et al. (EP2385107 A1, date of filing, Mar. 05, 2010) as evidenced by USDA-CFSPH-2015 and in view of Girones et al. (Proc Natl Acad Sci U S A. 1989 Mar;86(6):1846-9) as applied on claims 1, 10-11, 14, 17, 18, 20-24, 26 and 30 above, and in view of Foley et al. (WO2006/074963 A2, published on July 20, 2006).
Claim 6 is directed to the nucleic acid sequence encoding an encapsidation element comprises SEQ ID NO: 10 and/or SEQ ID NO: 13, or a variant thereof.
Claim 7 is directed the nucleic acid sequence encoding an RRE comprises SEQ ID NO: 14, or variant thereof.
Relevance of Chaeneau et al. is set forth above. However, it is silent on the encapsidation element comprises SEQ ID NO: 10 and/or SEQ ID NO: 13, and RRE SEQ ID NO: 14.
Foley et al. teaches a new recombinant lentiviral gene transfer system that comprises plasmids comprising a nucleic acid sequence encoding polyprotein Visna lentivirus (VLV) Gag, Pol, Vif, Rev, and Tat proteins, useful for ribozyme-mediated repair of a target RNA (See page 5), where the Gag-leader sequence is SEQ ID NO. 16 (See e.g. page 20, paragraph 2) and the Gag-Leader (Gag-L) containing a packaging signal (See page 14, paragraph 4), where the packaging signal is also known as the Ψ RNA packaging signal or core encapsidation signal (ΨCES). The SEQ ID NO. 16 is identical to the claimed SEQ ID NO: 10 as follows (See Table 1 below):
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As for claim 7, Foley et al. teaches the nucleotide sequence of pBR322dtVLVt-f3Gal is listed in SEQ_ID No. 9 (See page 21, paragraph 6 and Table 2 below), which contains the claimed RRE SEQ ID NO: 14 at its regions of 3221bp to 3422bp that is the region of RRE/protein bind Rev response element (See page 49 <221> to ,223>).
It would have been prima facie obvious for one having ordinary skill in the art before the effective filing date of the claimed invention to use encapsidation elements known in the art such as SEQ ID NO: 16 of Foley as the encapsidation element of Charneau, which is identical to SEQ ID NO: 10 as claimed, and to use the RRE known in the art such as SEQ ID NO: 9 of Foley as the RRE of Charneau, which contains the SEQ ID NO: 14 as claimed. One of skill in the art would have been motivated to use the known Visna packaging signal sequence that is contained in the gag-leader (Gag-L) sequence of SEQ ID NO: 16, and use the known Visna virus RRE of SEQ ID NO: 9, and there would be a reasonable expectation of success to construct a plasmid comprise the nucleic acid sequence encoding an encapsidation element comprises SEQ ID NO: 10 of the small ruminant lentivirus nucleic acid sequences as claimed, and also including the RRE of SEQ ID NO: 14 of the small ruminant lentivirus nucleic acid sequences as claimed.
Regarding claims 12 and 13, they require system further comprising an additional plasmid comprising a nucleic acid sequence encoding a rev protein, where the nucleic acid sequence encoding the rev protein is a small ruminant lentivirus nucleic acid sequence.
Relevance of Chaeneau et al. is set forth above. However, it is silent on the lentiviral vector system further comprising an additional plasmid comprising a nucleic acid sequence encoding a rev protein and the rev protein is a small ruminant lentivirus nucleic acid sequence.
Foley et al. teaches a fourth plasmid comprising sequences encoding VLV Vif, ReV, and Tat (See Abstract), where VLV (Visna lentivirus) is a small ruminant lentivirus (Claim 13). Foley et al. further teaches that the proteins Pol, Vif, Rev and Tat are required for the proper function of the recombinant lentiviral gene transfer system, and the Pol, accessory (Vif, Rev and Tat) and structural protein coding sequences (Gag) are separated from the transfer plasmid on 3 separate plasmids. By separating the genome of the construct over a number of plasmids the risk of the production of a replication competent retrovirus from the inventive gene transfer construct is reduced, as the number of recombination events, required is increased (See page 5).
It would have been prima facie obvious for one having ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Charneau and Foley to arrive at an invention as claimed. Because Foley teaches separating the genome of the construct can reduce the risk of recombination events. One of skill in the art would have been motivated to apply the fourth plasmid containing REV protein gene into Charneau’s invention, and there would be a reasonable expectation of success to construct a lentiviral vector system further comprising plasmid expressing a REV protein.
(New rejection) Claim 9 is rejected under 35 U.S.C. 103 as being unpatentable over Charneau et al. (EP2385107 A1, date of filing, Mar. 05, 2010) as evidenced by USDA-CFSPH-2015 and in view of Girones et al. (Proc Natl Acad Sci U S A. 1989 Mar;86(6):1846-9) as applied on claims 1, 10-11, 14, 17, 18, 20-24, 26 and 30 above, and in view of M31646-NCBI ( https://www.ncbi.nlm.nih.gov/nuccore/M31646.1).
Claim 9 is directed to the nucleic acid sequence encoding a gag polyprotein and a gag-pol polyprotein comprises SEQ ID NO:24, or a variant thereof.
Relevance of Chaeneau et al. is set forth above, However, it is silent on a promoter comprises SEQ ID NO: 24, or a variant.
M31646-NCBI teaches the complete genome; envelope protein; gag protein; pol polyprotein; reverse transcriptase; tat protein and discloses that the CDS region for gag polyprotein is at 520bp to 1860bp, and the CDS for Pol polyprotein is from 2076bp to 5051bp (See page 1), where the Gag and Pol sequence share 74.9% identity to the claimed 24 (See Table D below). Although the sequence differences are presented , it is a sequence encoding the Gag and Pol that can be a “variant thereof” of the claimed SEQ ID
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NO: 24.
It would have been prima facie obvious for one having ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Charneau and M31646-NCBI to arrive at an invention as claimed. One of skill in the art would have been motivated to use the known variant of the SEQ ID NO: 24 of M31646-NCBI to substitute the Gag and Pol of Charneau and construct a lentiviral vector system as claimed (See MPEP 2144.06: Substituting equivalents known for the same purpose). There would be a reasonable expectation of success to construct such a lentiviral vector system/particle comprising the variant of SEQ ID NO: 1 as claimed based on the techniques taught by Charneau and the sequences released by M31646-NCBI.
Claims 25 is rejected under 35 U.S.C. 103 as being unpatentable over Charneau et al. (EP2385107 A1, date of filing, Mar. 05, 2010) as evidenced by USDA-CFSPH-2015 and in view of Girones et al. (Proc Natl Acad Sci U S A. 1989 Mar;86(6):1846-9) as applied on claims 1, 10-11, 14, 17, 18, 20-24, 26 and 30 above and further as evidenced by Mendiloa et al. (Biomed Res Int. 2019 May 12;2019:4279573).
Regarding claim 25, it requires that the lentiviral vector system according to claim1, wherein the portion of the 3' long terminal repeat does not contain a TATA box nucleic acid sequence.
Charneau et al. does not explicitly use the term of “TATA box” in their invention, but Charneau et al. teaches that in another particular embodiment, the 3’ LTR region is devoid of the U3 region (delta U3) (See e.g. [0090]). It is a common knowledge in the art that the TATA box is situated within the U3 region of the 3’ LTR. This is evidenced in Mendiloa et al. which teaches that the TATA box is located in the U3 region and it is an important element as a promoter of transcription (See page 7, left column, paragraph 1).
(New Rejection-necessitated by amendment) Claim 28 is rejected under 35 U.S.C. 103 as being unpatentable over Charneau et al. (EP2385107 A1, date of filing, Mar. 05, 2010) as evidenced by USDA-CFSPH-2015 and in view of Girones et al. (Proc Natl Acad Sci U S A. 1989 Mar;86(6):1846-9) as applied on claims 1, 10-11, 14, 17, 18, 20-24, 26 and 30 above, and in view of Bray et al. (Proc Natl Acad Sci U S A. 1994 Feb 15;91(4):1256-60) and Wodrich et al. (Nucleic Acids Res. 2000 Feb 15;28(4):901-10).
Claim 28 is directed to a lentiviral vector system according to claim 1, wherein the packaging plasmid comprises a nucleic acid sequence encoding one or more Mason Pfizer monkey virus constitutive transport elements (CTE) downstream of the nucleic acid sequence encoding the gag and gag-pol polyproteins.
Relevance of claim 1 and claim 8 are set forth above. However, they are silent on a Mason Pfizer monkey virus constitutive transport elements (CTE) at downstream of the nucleic acid sequence encoding the gag and gag-pol polyproteins.
Bray et al. describes a small element from the Mason-Pfizer monkey virus (MPMV) genome that makes HIV-1 expression and replication Rev-independent, and teaches that MPMV element is also able to efficiently substitute for Rev in expression of Gag/Pol and Env proteins from subgenomic constructs. It might be possible to exploit this element in the development of an HIV vaccine (See Abstract) because Bray et al. teaches to use the MPMV element have been able to generate a variant of HIV-1 that replicates with an attenuated phenotype in tissue culture cells (See page 1260, left column, paragraph 7). Bray et al. names the MPMV element as CTE (constitutive transport element) (See page 1260, left column, paragraph 2). The construct of the CTE at the downstream of Gag/Pol taught by Bray as follows:
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Wodrich et al. teaches that multimer copies of the MPMV CTE (constitutive transport elements) leads to enhanced Rev-independent HIV-I Gag production in a context-dependent way. Wodrich et al. discloses that gag polyprotein (Pr55) expression can be significantly elevated if multiple copies of the Mason-Pfizer CTE were incorporated into the gag-pol expression plasmid compared to a single copy of the CTE, which may circumvent the requirement of the rev/RRE post-transcriptional control systems in vector production (See e.g. page 903, right column, paragraph 4; Figure 1, page 904 and Figure 2, page 905; table 1 and below).
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It would have been prima facie obvious for one having ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings from Charneau, Bray and Wodrich to arrive at an invention as claimed. Charneau teaches a packing plasmid comprising Gag and Gag-Pol, which is one of the vectors that is used to generate the Lentiviral particles for therapy and vaccine application. Bray and Wodrich teach inserting the MPMV CTE under the downstream of gag and gag-pol and disclose the benefit as attenuating the virus and also enhance the expression of Gag/Pol. Therefore, one of skill in the art would have been motivated to apply the MPMV CTE and its cloning method into Charneau’s invention, and there would be a reasonable expectation of success to construct a lentiviral vector system as claimed.
Allowable Subject Matter
The nucleic acid sequence SEQ ID Nos: 1-2 and 24 are free of prior art.
Responses to Applicant’s Remarks
Applicant’s arguments filed on Dec. 02, 2025 has been received and fully considered.
Applicant’s argument on rejection under 35 U.S.C. § 112 is considered and the rejection is withdrawn for claim 26.
Applicant’s arguments on rejection under 35 U.S.C. § 102 is considered and the rejection is withdrawn.
Applicant’s argument on rejections under 35 U.S.C. § 103 based on the SEQ ID NO: 1 newly added in the base claims 1 and 14 are not found persuasive. Although the SEQ ID NO: 1 is free of art, the limitation “variant thereof” of SEQ ID NO:1 raised a new rejection under 35 U.S.C. § 112, and the new prior arts are cited for teaching the variant of SEQ ID NO: 1 as well.
Conclusion
No claims are allowed.
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/RUIXUE WANG/Examiner, Art Unit 1672
/NICOLE KINSEY WHITE/ Primary Examiner, Art Unit 1672