DETAILED ACTION
Claims 1-20 from the claim set filed 3/23/20223 are pending. Claims 21-22 are cancelled. Claims 15-20 are withdrawn. Claims 1-14 are being examined on the merits herein.
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 .
Election/Restrictions
Applicant's election with traverse of Group I, claims 1-16 in the reply filed on January 6, 2026 is acknowledged. The traversal is on the ground(s) that the identified technical feature is both novel and non-obvious over the cited art and further that the search and examination of the entire application could be made without serious burden.
Upon further thought and consideration, Examiner agrees the disclosure of Sirion alone (i.e., the previously applied prior art) does not teach the instant invention. However, the disclosures of Sirion and Zhang, as evidenced by Goyvaerts, do teach the instant invention and as such the technical feature is not novel and non-obvious. Please see the 103 rejection of claim 1 below for specific details and reasoning.
In regards to Applicant remarks concerning search burden, Examiner respectfully notes the discussion of unity of invention under the Patent Cooperation Treaty Articles and Rules as it is applied as an International Searching Authority, International Preliminary Examining Authority, and in applications entering the National Stage under 35 U.S.C. 371 as a Designated or Elected Office in the U.S. Patent and Trademark Office is covered in M.P.E.P. §1850 and is dictated by PCT Rules 13.1 and 13.2. See M.P.E.P. §801. Burden is not a consideration in a finding of lack of inventive unity; rather, according to M.P.E.P. §1850, the only consideration is whether the inventions share a special technical feature.
As such, Applicants’ traversal has been carefully considered, but fails to be persuasive in establishing the impropriety of the restriction requirement and thus, the requirement is still deemed proper and is therefore made FINAL.
In regards to the election of species, a phone call was made on 1/28/2026 to Applicant’s representative (Joel Armstrong, Reg No. 36,430) to discuss the election of species and to further clarify what the office action filed on 11/6/2025 was requiring. Subsequently, Applicant’s representative authorized the election of species (a), claims 10-13, via a phone call on 1/29/2026.
Thus, claims 1-14 will be examined on the merits herein.
Claims 15-20 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.
Priority
A claim for benefit of a prior-filed application under 35 U.S.C. 119(a)-(f) or under 35
U.S.C. 120, 121, 365(a)-(c), 386 (a) or 386(c) has been made. The effective filing date of the
present application is September 30, 2020.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on March 23, 2023 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Drawings
The drawings are objected to because the drawings are indicated by “Figure” rather than “FIG.” as required by 37 C.F.R § 1.84 (u)(1) (see also MPEP § 608.02 (V)). The different views must be numbered in consecutive Arabic numerals, starting with 1, independent of the numbering of the sheets and, if possible, in the order in which they appear on the drawing sheet(s). Partial views intended to form one complete view, on one or several sheets, must be identified by the same number followed by a capital letter. View numbers must be preceded by the abbreviation “FIG.” Where only a single view is used in an application to illustrate the claimed invention, it must not be numbered and the abbreviation “FIG.” must not appear.
Appropriate correction is required.
Double Patenting
Claims 1-4, 6-12, and 14-16 are provisionally rejected on the grounds of nonstatutory double patenting as being unpatentable over claims 32-35, 37, and 39-46 of copending Application No. 18/730,924 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because claims 32-35, 37, and 39-46 of the reference application anticipate claims 1-4, 6-12, and 14-16 of the instant application.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Instant Application
18/730,924
Claim 1: A group of viral vectors, comprising:
a first viral vector, wherein the first viral vector carries a first nucleic acid molecule, and the first nucleic acid molecule encodes an envelope protein;
at least a second viral vector, wherein the second viral vector carries a second nucleic acid molecule, the second nucleic acid molecule encodes at least one fusion protein, the fusion protein includes at least one single-chain antibody and the C-terminal domain of the envelope protein, the C-terminal domain of the envelope protein includes a transmembrane region and a intracellular region of the envelope protein, the C-terminus of the at least one single-chain antibody connects with the N-terminus of the C-terminal domain of the envelope protein, the single-chain antibody targets a specific antigen;
the first nucleic acid molecule and the second nucleic acid molecule are arranged to express the envelope protein and the fusion protein, and the envelope protein and the fusion protein are in a non-fusion form.
Claim 2: The viral vectors according to claim 1, wherein the viral vectors are retrovirus vectors, lentivirus vectors or other enveloped virus vectors.
Claim 3: The viral vectors according to claim 1, wherein the enveloped virus comprises at least one selected from: Bornaviridae, Nyamaviridae, Arenaviridae, Filoviridae, Hantaviridae, Nairoviridae, Orthomyxoviridae, Paramyxoviridae, Bunyaviridae, Phenuiviridae, Rhabdoviridae, Arteriviridae, Coronaviridae, Flaviviridae, Togaviridae, Hepadnaviridae, Spumavirus, Iridoviridae, Herpesviridae, Poxviridae, and Deltavirus; optionally, the envelope protein is an envelope G glycoprotein or a mutant of envelope G glycoprotein of vesicular stomatitis virus of the Rhabdoviridae.
Claim 4: The viral vectors according to claim 3, wherein the mutant of the envelope G glycoprotein has K47Q and R354Q mutations; optionally, the mutant of the envelope G glycoprotein has the amino acid sequence shown in SEQ ID NO: 1.
Claim 6: The viral vectors according to claim 1, wherein the fusion protein further comprises a first connecting peptide…
Claim 7: The viral vectors according to claim 1, further comprising: a first promoter, which is operably linked to the first nucleic acid molecule; and a second promoter, which is operably linked to the second nucleic acid molecule.
Claim 8: The viral vectors according to claim 7, wherein each of the first promoter and the second promoter is independently selected from CMV, EF-1, and RSV promoters.
Claim 9: The viral vectors according to claim 1, wherein the first nucleic acid molecule has the nucleotide sequence shown in SEQ ID NO: 5
Claim 10: The viral vectors according to claim 1, wherein the first viral vector and the second viral vector are the same vector.
Claim 32: A group of viral vectors, comprising:
a first viral vector, wherein the first viral vector carries a first nucleic acid molecule, and the first nucleic acid molecule encodes an envelope protein;
at least a second viral vector, wherein the second viral vector carries a second nucleic acid molecule, the second nucleic acid molecule encodes at least one fusion protein, the fusion protein includes at least one single chain antibody and the C-terminal domain of the envelope protein; the single chain antibody is capable of binding to CD28 or CD3, the C- terminal domain of the envelope protein includes a transmembrane region and a intracellular region of the envelope protein, the C-terminal of the at least one single chain antibody is connected to the N-terminal of the C-terminal domain of the envelope protein;
the first nucleic acid molecule and the second nucleic acid molecule are arranged to express the envelope protein and the fusion protein, and the envelope protein and the fusion protein are in a non-fusion form.
*Examiner notes CD28 and CD3 are specific antigens, thus claim 32 of ‘924 anticipates claim 1 of the IA.
Claim 33: The viral vectors according to claim 32, wherein the viral vectors are retroviral vectors, lentiviral vectors or other enveloped viral vectors
Claim 34: The viral vectors according to claim 33, wherein the enveloped virus comprises at least one selected from the group consisting of: Bornaviridae, Nyamaviridae, Arenaviridae, Filoviridae, Hantaviridae, Nairoviridae, Orthomyxoviridae, Paramyxoviridae, Bunyaviridae, Phenuiviridae, Rhabdoviridae, Arteriviridae, Coronaviridae, Flaviviridae, Togaviridae, Hepadnaviridae, Spumavirus, Iridoviridae, Herpesviridae, Poxviridae and Deltavirus;optionally, the envelope protein is an envelope G glycoprotein or a mutant variant thereof from a vesicular stomatitis virus belonging to the family Rhabdoviridae; optionally, the envelope G glycoprotein has an amino acid sequence shown in SEQ ID NO:1.
Claim 35: The viral vectors according to claim 34, wherein the mutant of the envelope protein has a mutation that weakens the attachment capacity; optionally, the mutant of the envelope G glycoprotein has K47Q and R354Q mutations; optionally, the mutant of the envelope G glycoprotein has an amino acid sequence shown in SEQ ID NO: 2.
Claim 37: The viral vectors according to claim 32, wherein the fusion protein further comprises a first linking peptide, wherein the N-terminal of the first linking peptide is connected to the C-terminal of the first single chain antibody, and the C-terminal of the first linking peptide is connected to the N-terminal of the second single chain antibody; or…
Claim 39: The viral vectors according to claim 32, wherein the viral vector further comprises: a first promoter, which is operably linked to the first nucleic acid molecule; and a second promoter, which is operably linked to the second nucleic acid molecule; optionally, each of the first promoter and the second promoter is independently selected from CMV, EF-1 or RSV promoters.
Claim 40: The viral vectors according to claim 32, wherein the first nucleic acid molecule has a nucleotide sequence shown in SEQ ID NO: 21…
*Examiner notes SEQ ID NO: 21 and SEQ ID NO: 5 of the instant application have 100% sequence identity
Claim 41: The viral vectors according to claim 32, wherein the first viral vector and the second viral vector are the same vector.
Although not presented in the table above, Examiner notes claim 42 of ‘924 is the same as claim 11 of the instant application (IA), claim 43 of ‘924 is the same as claim 12 of the IA, claim 44 of ‘924 is the same as claim 14 of the IA, claim 45 of ‘924 is the same as claim 15 of the IA, and claim 46 of ‘924 is the same as claim 16 of the IA. Due to claims 17-20 being withdrawn from the instant application, Examiner has not compared said claims.
Therefore, as the table presented supra evidences, claims 32-35, 37, and 39-46 of the reference application anticipate claims 1-4, 6-12, and 14-16 of the instant application.
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.
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.
Claim 3 is rejected under 35 U.S.C. 112(b), as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 3 recites the limitation "the" enveloped virus. Claim 3 depends from claim 1 in which there is no mention of enveloped virus but instead refers to viral vectors carrying envelope proteins or portions of envelope proteins. There is insufficient antecedent basis for this limitation in the claim.
Thus, the claim is properly rejected as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, regards as the invention.
In the interest of compact prosecution, claim 3 is interpreted as “wherein the enveloped protein comprises”. However, despite the above interpretation, such treatment does not relieve Applicant of the responsibility of responding to this rejection. If the actual interpretation of the claims is different than that posited by the Examiner, additional rejections and art may be readily applied in a subsequent final Office action.
Claim 13 is rejected under 35 U.S.C. 112(b), 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 13 recites an example that lends confusion over the intended scope of the claim. As stated in the MPEP 2173.05(d), “If stated in the claims, examples and preferences may lead to confusion over the intended scope of a claim. In those instances where it is not clear whether the claimed narrower range is a limitation, a rejection under 35 U.S.C. 112(b) second paragraph should be made.”
In the present instance, claim 13 recites “preferably, the ratio of the copy number…” which is a narrow range limitation that appears to be a preference or example within the broad recitation of the ratio copy number.
The claim is considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claim. The claim is indefinite because of containing a combination of a broad range and narrow range that appears to be an example or preference and not a true alternative embodiment.
Thus, the claim is properly rejected as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, regards as the invention.
In the interest of compact prosecution, Examiner reads “preferably” as optional. However, despite the above interpretation, such treatment does not relieve Applicant of the responsibility of responding to this rejection. If the actual interpretation of the claims is different than that posited by the Examiner, additional rejections and art may be readily applied in a subsequent final Office action.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1-3, 5-8, 10, 13, and 14 are rejected under 35 U.S.C. 103 as being unpatentable over Sirion Biotech GMBH [henceforth Sirion] (US 2016333374 A1, published November 17, 2016; cited in the International Written Opinion of the International Searching Authority, filed March 23, 2023; PTO 892) in view of Zhang (Zhang et al., Retrovirology (2010), 7:3; PTO 892), as evidenced by Goyvaerts (Goyvaerts et al., Gene Ther (2012), 12(19); PTO 892).
Claim 5 is rejected under 35 USC 103 as being unpatentable over Sirion, in view of Zhang, as evidenced by Goyvaerts, and as further evidenced by Bisig (Bisig et al., Best Practice and Research Clinical Haematology (2012) 25:13-28; PTO 892).
In regards to claims 1-3, Sirion teaches [0001] the present invention relates to a nucleic acid molecule comprising or consisting of a nucleic acid sequence encoding the vesicular stomatitis virus envelope glycoprotein (VSV-G) linked to a (poly)peptide comprising or consisting of a cell membrane-binding domain, said nucleic acid sequence comprising in 5' to 3' direction (a) a first sequence segment encoding an endoplasmic reticulum (ER) signal sequence [denoted as SSHis, Fig 1]; (b) a second sequence segment encoding said (poly)peptide comprising or consisting of a cell membrane-binding domain [denoted as scFv, Fig 1]; (c) a third sequence segment encoding a linker, and (d) a fourth sequence segment encoding said VSV-G (Fig 1). Further, the invention relates to a vector comprising the nucleic acid molecule of the invention, a host cell comprising said vector or nucleic acid molecule, the polypeptide encoded by said nucleic acid molecule and a method of producing the polypeptide encoded by said nucleic acid molecule. In addition, the invention relates to a pseudotyped lentiviral vector particle, a method of transducing a cell as well as a kit comprising various combinations of the nucleic acid molecule [0001].
To summarize Fig 1, Sirion teaches a group of lentiviral vectors (i.e., claim 2). Sirion teaches a first lentiviral vector which carries a first nucleic acid molecule which encodes VSV-G protein (i.e., an envelope protein) (noted as wt-VSV-G) of the Rhabdoviridae family [0036] (i.e., claim 3)and a second lentiviral vector which carries a second nucleic acid molecule which encodes a fusion protein wherein the fusion protein includes one single chain antibody and VSV-G protein, wherein the C-terminus of the single chain antibody connects with the N-terminus of the VSV-G protein through a linker (noted as scFv-VSV-G Fusion).
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Sirion additionally teaches the single chain antibody targets CD30 or EGFR on the cell membrane (i.e., the single-chain antibody targets a specific antigen) [0028].
Sirion further teaches the sequence of the VSV envelope glycoprotein is well-known in the art and includes, in accordance with the invention, a cytoplasmic tail (i.e., an intracellular region), a transmembrane domain and a membrane-proximal extracellular stem region (ectodomain or extracellular domain) that mediates efficient virus budding. VSV-G sequences have been described in the art, e.g., in [54] and the NCBI Reference number of the naturally occurring VSV-G is NP-955548.1 (NCBI Genome Project, 2000) [0036].
As can moreover be seen in Fig 1, Sirion additionally teaches the first nucleic acid molecule and the second nucleic acid molecule are operably linked to the CMV promoter separately and expressed in a non-fusion form.
Sirion does not teach wherein the C-terminus of the single-chain antibody connects with the N-terminus of the C-terminal domain of the envelop protein, but rather teaches wherein the C-terminus of the single chain antibody connects with the N-terminus of the full VSV-G protein.
Zhang teaches of targeted cell transduction being achieved using lentiviral vector particles bearing a membrane-bound form of SCF in conjunction with an independent fusion domain derived from VSV-G (p2, last paragraph column 1-1st paragraph column 2). Zhang teaches an alternative lentiviral vector targeting strategy in which a membrane-bound form of SCF is incorporated into EGFP-encoding lentiviral particles (LV-EGFP) containing a truncated version of the VSV-G glycoprotein (VSV-GS). VSV-GS consists of a truncated ectodomain bearing the membrane-proximal stem region and the native trans-membrane and cytoplasmic domains (Fig 2A). Zhang teaches the VSV-GS protein was previously shown to enhance the cell-cell fusion activity of heterologous Env proteins. Zhang further teaches LV-EGFP particles bearing VSV-GS resulted in specific transduction of 293 cells, thus teaching of cell specific targeting using lentiviral particles displaying human SCF and a fusion domain derived from VSV-G (p3, 1st column, Cell specific targeting).
Zhang, Fig 2A
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In regards to the truncated ectodomain, Examiner notes Zhang teaches the truncated ectodomain bears the membrane-proximal stem region. Examiner further notes, and as a POSITA will appreciate, it is generally considered that the C-terminal domain includes the stem region.
In addition, Examiner notes Goyvaerts teaches of the plasmid pUB6-VSV.GS, and notes said plasmid which encodes the binding-defective, but fusion competent VSV.GS was described by Zhang and is schematically represented in Supplementary Figure 1A (p1138, 2nd column, LV production).
Goyvaerts, Supplementary Fig 1A
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Examiner notes said figure makes clear VSV-GS does not comprise the N-terminal domain of VSVG but rather comprises the stem residues, transmembrane domain and cytoplasmic tail, i.e., the C-terminal domain. Thus, Goyvaerts evidences the VSV-GS of Zhang encompasses the stem region, transmembrane domain and cytoplasmic tail of VSV-G, i.e., the C-terminal domain.
Thus, it would have been obvious to a POSITA, before the effective filing date of the claimed invention, to modify the teachings of Sirion with the teachings of Zhang and Goyvaerts. A POSITA would have been so motivated due to Zhang teaching of the VSV-GS protein showing enhanced cell-cell fusion activity and LV-EGFP particles bearing VSV-GS resulting in specific transduction of 293 cells, and thus teaching of cell specific targeting via VSV-GS. A POSITA would have been motivated to modify the VSV-G envelope protein taught by Sirion to comprise the VSV-GS envelope protein taught by Zhang which comprises solely the C-terminal domain of VSV-G rather than the full length of VSV-G. A POSITA would have had a reasonable expectation of success in combining said teachings due to all working in the field of lentiviral transduction.
Thus, the claims are obvious and are properly rejected.
In regards to claim 5, Sirion teaches the single chain antibody targets CD30 or EGFR on the cell membrane [0028]. As is evidenced by Bisig, and as a POSITA will appreciate, a single chain antibody targeting CD30 is considered to target a cell-specific antigen as CD30 is expressed by B and T immunoblasts and is a hallmark feature of ALCLs and of the primary cutaneous CD30+ T-cell lymphoproliferative disorders (p19, last paragraph).
Thus, the claim is obvious and is properly rejected.
In regards to claim 6, Sirion teaches [0001] the present invention relates to a nucleic acid molecule comprising or consisting of a nucleic acid sequence encoding the vesicular stomatitis virus envelope glycoprotein (VSV-G) linked to a (poly)peptide comprising or consisting of a cell membrane-binding domain, said nucleic acid sequence comprising in 5' to 3' direction (a) a first sequence segment encoding an endoplasmic reticulum (ER) signal sequence [denoted as SSHis, Fig 1]; (b) a second sequence segment encoding said (poly)peptide comprising or consisting of a cell membrane-binding domain [denoted as scFv, Fig 1]; (c) a third sequence segment encoding a linker (i.e., a first connecting peptide) (i.e., claim 6), and (d) a fourth sequence segment encoding said VSV-G (Fig 1).
As noted in the instant specification, [0017] “According to the embodiments of the present invention, the fusion protein further comprises a first connecting peptide. Thereby, the single-chain antibody region is separated from the C-terminal region of the envelope protein to reduce frictional interference between the two.”
Thus, the third segment encoding a linker reads on a first connecting peptide. As such, the claim is obvious and is properly rejected.
In regards to claims 7 and 8, Sirion teaches (Fig 1), the first nucleic acid molecule and the second nucleic acid molecule are operably linked to the CMV promoter separately and expressed in a non-fusion form.
Thus, the claims are obvious and are properly rejected.
In regards to claims 10 and 13, Sirion teaches wherein the first viral vector and the second viral vector are the same vector, i.e., pMD2.G [0165].
Examiner notes the claim language as currently written does not require the first nucleic acid molecule and the second nucleic acid molecule to be carried within the same vector, i.e., both nucleic acid molecules in one vector rather than in two separate vectors, but instead requires the first viral vector and the second viral vector to be the same vector, i.e., the same type of vector such as pMD2. G. Thus, as noted supra, Sirion teaches of pMD2. G.
However, in the interest of compact prosecution, Examiner believes based upon the dependent claims, that Applicant wishes to convey that the first and second nucleic acid molecules are in carried within one viral vector.
Examiner notes Sirion teaches wherein the first nucleic acid molecule and the second nucleic acid molecule are within the same vector. Sirion teaches in accordance with the present invention, a lentivirus vector particle is provided that is pseudotyped with two different types of VSV-G proteins, namely with the fusion protein of the invention described herein above (option (a), i.e., Fig 1 scFv-VSV-G) and with a VSV-G that has not been fused to a cell membrane-binding domain, i.e. a wild-type (wt) VSV-G (option (b), i.e., Fig 1 wt VSV-G). In other words, each individual lentivirus vector particle expresses both modified and wild type VSV-G glycoproteins on its surface [0094]. Sirion teaches it was surprisingly found that pseudotyping with both these VSV-Gs is advantageous over the use of one of these proteins alone. First, the use of 100% of the VSV-G fusion protein of the invention failed to infect cells in cytometric assays, as shown e.g. in Example 4, thus not achieving the intended transduction. Second, as is also shown in the appended examples, a mixture of the inventive molecule with wt molecules led to enhanced infection rates as compared to wild type alone [0095].
Additionally, in regards to claim 13, Sirion teaches in a preferred embodiment of the lentivirus vector particle of the invention, the ratio of (a): (b) exhibited by said pseudotyped lentiviral vector particle in the viral envelope is between 10%:90% and 50%:50% [0096]. Examiner notes 50%:50% reads on a 1:1 ratio. Thus, the claimed ranges of claim 13, i.e., 1:1 – 4:1, overlap. In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). MPEP 2144.05
Thus, the claims are obvious and are properly rejected.
In regards to claim 14, Sirion teaches wherein the first viral vector and the second viral vector are pMD2.G [0165].
Thus, the claim is obvious and is properly rejected.
Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Sirion Biotech GMBH [henceforth Sirion], in view of Zhang, as evidenced by Goyvaerts, and further in view of Nikolic (Nikolic, et al., Nature Communications (2018) 9: 1029; PTO 892).
In regards to claim 4, the above cited references do not teach “wherein the mutant of the envelope G glycoprotein has K47Q and R354Q mutations.
Nikolic teaches of vesicular stomatitis virus (VSV) and its glycoprotein G and notes VSV-G it is widely used to pseudotype other viruses for gene therapy. Nikolic further teaches low-density lipoprotein receptor (LDL-R) serves as the major entry receptor for VSV. Nikolic additionally teaches of two basic residues on G (i.e., VSV-G) which are essential for its interaction with CR2 and CR3 (i.e., two distinct cysteine-rich domains) of LDL-R. Mutating these residues abolishes VSV infectivity even though VSV can use alternative receptors, indicating that all VSV receptors are members of the LDL-R family. Nikolic further teaches these structural insights into the interaction between VSV-G and host cell receptors provide a basis for the design of recombinant viruses with an altered tropism (Abstract).
Nikolic teaches the two basic residues on G which are essential for its interaction with CR2 and CR3 are K47 and R354. Nikolic further teaches of mutating said residues to study their contribution to LDL-R CR binding. Nikolic teaches of the mutants K47Q and R354Q (p7, 2nd column, last paragraph). Nikolic teaches mutants K47Q and R354Q do not bind to either CR2 or CR3 (p8, 1st column, 1st paragraph). Thus, mutants K47Q and R354Q cannot bind to LDL-R receptors. Nikolic additionally teaches said mutants maintain a fusion phenotype similar to that of WT G (p8, 2nd column, 1st paragraph).
Thus, it would have been obvious to a POSITA, before the effective filing date of the claimed invention, to combine the teachings of the above cited references with the teachings of Nikolic. A POSITA would have been so motivated due to the above cited references utilizing single-chain antibodies to target specific antigens. By eliminating the LDL-R binding of VSV-G (as taught by Nikolic), the fusion protein would thus solely bind to the antigens targeted by the single chain antibodies (as taught by the above cited references) thus providing specific cell specificity. A POSITA would thus have found it obvious to utilize a VSV-G mutant comprising K47Q and R354Q, rather than a wild type VSV-G as taught by the above cited references. A POSITA would have further been motivated to combine said teachings due to Nikolic teaching of said VSV-G mutants as a basis for the design of recombinant viruses with an altered tropism. A POSITA would have had a reasonable expectation of success in combining said teachings due to all working in the field of recombinant viruses.
Thus, the claim is obvious and is properly rejected.
Claims 11-12 are rejected under 35 U.S.C. 103 as being unpatentable over Sirion Biotech GMBH [henceforth Sirion], in view of Zhang, as evidenced by Goyvaerts, and further in view of Fan (Fan, M., Addgene Blog (2014), retrieved from (https://blog.addgene.org/plasmids-101-multicistronic-vectors#:~:text=IRES%20Elements,a%20time%20using%20IRES%20elements.) on Feb 3, 2026; PTO 892).
In regards to claim 11, Sirion, Zhang and Goyvaerts teach the viral vector of claim 10. The above cited references do not teach an IRES is arranged between the first and second nucleic acid molecule.
The language of claim 11 reads on a multicistronic vector. As a POSITA will appreciate, and as is taught by Fan, multicistronic vectors commonly include IRES elements between the two genes of interest, i.e., between the first nucleic acid molecule and the second nucleic acid molecule. Fan teaches IRES elements are very useful and commonly found in bicistonic vectors (p2).
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Thus, it would have been obvious to a POSITA, before the effective filing date of the claimed invention, to combine the teachings of Sirion and Zhang with the teachings of Fan in order to have a multicistronic vector (as taught by Fan) expressing the two nucleic acids of the instant invention (as taught by Sirion and Zhang). A POSITA would have been so motivated due to Fan teaching the use of multicistronic vectors is very useful and common. A POSITA would have had a reasonable expectation of success in combining said teachings due to all working in the field of vectors.
Thus, the claim is obvious and is properly rejected.
In regards to claim 12, Sirion, Zhang and Goyvaerts teach the viral vector of claim 10. The above cited references do not teach a third nucleic acid molecule arranged between the first and second nucleic acid molecule, and the third nucleic acid molecule encodes a second connecting peptide and the second connecting peptide can be cleaved.
Fan teaches to overcome some of the disadvantages of the IRES element, scientists have adapted “self-cleaving” 2A peptides into their multicistronic vectors. These peptides are short and produce equimolar levels of multiple genes from the same RNA. Fan teaches the 2A peptide (i.e., a connecting peptide which can be cleaved, i.e., a second connecting peptide which can be cleaved) is located in the place of the IRES, which as is shown above, is located between the first and second nucleic acid molecules (p3).
Thus, it would have been obvious to a POSITA, before the effective filing date of the claimed invention, to combine the teachings of Sirion and Zhang with the teachings of Fan in order to have a multicistronic vector (as taught by Fan) expressing the two nucleic acids of the instant invention (as taught by Sirion and Zhang). A POSITA would have been so motivated due to Fan teaching the use of multicistronic vectors is very useful and common. Further, Fan teaches the use of either an IRES element or a 2A peptide. A POSITA would have had a reasonable expectation of success in combining said teachings due to all working in the field of vectors.
Thus, the claim is obvious and is properly rejected.
Conclusion
In regards to claim 9, Examiner acknowledges, after a thorough sequence search, that there is no prior art teaching 100% identity to SEQ ID NO: 5.
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/KATHERINE R SMALL/Examiner, Art Unit 1633
/EVELYN Y PYLA/Primary Examiner, Art Unit 1633