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 .
DETAILED ACTION
Acknowledgement is hereby made of receipt and entry of the communication filed on July 07, 2023. Claims 1-3, 5-6, 14, 19-22, 24-25, 33, 38, 50, 56, 62, 79 and 87-88 are pending and are currently examined.
Claim Objection
Claims 2, 5, 21 and 24 are objected to because of the following informalities: The phrase “… the nucleic acid encoding…” should be “the nucleic acid encodes”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112 (b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION. —The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-3, 5-6, 14, 19-22, 24-25, 33, 38, 50, 56, 62, 79 and 87-88 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
These claims recite “biologically active fragment” that renders the claims indefinite. It is unclear what the “biologically active fragment” refers to. One of ordinary skill in the art will not know the metes and bounds of the claims.
Regarding claims 6, 14, 25, 33, 38, 50, 56 and 88, the phrase "optionally" renders the claims indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(h).
The term optionally means "not required or mandatory". For example, a composition comprising A, B, C, and optionally D means that component D can or cannot be present (D is not required to be present). In the rejected claim, however, it appears the use of "optionally" is an attempt to define "preferred" embodiments or limitations. For example, claim 88 states “…the subject is a mammal, optionally a human, a primate, or a rodent, optionally a human…”, in this instance, the term optionally does not make sense given the definition of optionally (not required or mandatory). Accordingly, one of ordinary skill in the art will not know the metes and bounds of the claim.
Regarding claim 38, it recites a term “…efficient spread…” that renders the claim indefinite. It is not clear what the standard is for a “efficient spread”. Therefore, one of ordinary skill in the art will not know the metes and bounds if a particular spread is efficient.
Claim Rejections - 35 USC § 112 (Enablement)
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.
Claims 62 and 87 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 enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims.
Claims 62 and 87 contain subject matter which was not described in the specification in such a way as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims. Enablement is considered in view of the Wands factors (MPEP 2164.01(a)) (1) the nature of the invention, (2) the state of the prior art, (3) the breadth of the claims, (4) the amount of guidance in the specification, (5) the presence or absence of working examples, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) and the quantity of experimentation necessary.
A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557,1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993).
Claims 62 and 87 are directed to a method for identifying an agent that prevents and/or treats SARS- CoV-2 infection, and a method of preventing and/or treating SARS-CoV-2 infection in a subject comprising administering to the subject a therapeutically effective amount of an immunogenic composition comprising the rVSV-SARS-CoV-2 S as claimed, respectively.
The instant specification discloses a method for constructing the rVSV-SARS-CoV-2 S as claimed (See Example 1, [0173] to [0191]) and Example 2, [0192] to [0193]) and identifies the entry of the rVSV-SARS-CoV-2 S resembling the authentic agent (See Examples 3-6). At the same time, the instant specification also discloses that the rVSV-SARS-CoV-2 S can be used to rapidly and faithfully assess the neutralizing activities of large panels of COVID (See Examples 7-8). However, the instant specification does not provide experimental supports to demonstrate a method that the rVSV-SARS-CoV-2 S can be used for identifying an agent that prevents SARS- CoV-2 infection. Also, the instant specification does not provide experimental supports to demonstrate that the rVSV-SARS-CoV-2 S can be used to prevent SARS-CoV-2 infection in a subject.
Accordingly, when all the aforementioned factors are considered in total, it would require undue experimentation for one skilled in the art to practice the full scope of claimed invention as defined by instant claims 62 and 87.
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.
Claims 1-3, 5-6, 14, 19-22, 24-25, 33, 38, 62 and 79 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Dieterle et al. (bioRxiv preprint doi: https://doi.org/10.1101/2020.05.20.105247; this version posted May 20, 2020).
The base claim 1 is directed to a recombinant vesicular stomatitis virus (VSV) vector comprising a nucleic acid encoding spike glycoprotein S of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), or biologically active fragment.
The base claim 20 is directed to a recombinant vesicular stomatitis virus (VSV) comprising a genome which comprises a nucleic acid encoding spike glycoprotein S of SARS-CoV-2, or biologically active fragment.
Dieterle et al. teaches the base claim 1 by stating that a plasmid encoding the VSV antigenome was modified to replace its native glycoprotein, G, with the full-length wild-type S glycoprotein gene of the Wuhan-Hu-1 isolate of SARS-CoV-2 (GenBank MN908947.3) (See page 21, paragraph 3), where the plasmid is a type of vector.
Dieterle et al. teaches the base claim 20 by stating that to generate a replication-competent rVSV expressing SARS-CoV-2 S, they replaced the open reading frame of the native VSV entry glycoprotein gene, G, with that of the SARS-CoV-2 S (Wuhan-Hu-1 isolate) (Fig. 1A). They also introduced a sequence encoding the enhanced green
fluorescent protein (eGFP) as an independent transcriptional unit at the first position of the VSV genome (See page 6, paragraph 1; Fig 1 and below), which also teaches the claims 14 and 33 for encoding a reporter gene eGFP, claim 19 for a rVSV generated from the recombinant VSV vector and claim 38 for the rVSV is replication-competent.
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Regarding claims 2 and 21, Dieterle et al. teaches that the plasmid encoding the VSV antigenome was modified to replace its native glycoprotein, G, with the full-length wild-type S glycoprotein gene of the Wuhan-Hu-1 isolate of SARS-CoV-2 (See page 21. Paragraph 3).
Regarding claims 3 and 22, the spike protein encoded by Wuhan-Hu-1 isolate of SARS-CoV-2 (GenBank MN908947.3) (See page 21. Paragraph 3), QHD43416.1, is identical to the claimed SEQ ID NO: 1. (See Table 1 below).
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Regarding claims 5-6 and 24-25, Dieterle et al. teaches that rVSV vector contains the Spike mutation such as C1250 (See page 9 and Table S1).
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Regarding claims 62 and 79, Dieterle et al. teaches a method for identifying an agent that prevents and/or treats SARS- CoV-2 infection by stating that they compared the capacities of human antisera derived from 40 COVID-19 convalescent donors to block infection by rVSV-SARS-CoV-2 S and authentic SARS-CoV-2 in a microneutralization format (See page 13, paragraph 2), where the rVSV-SARS-CoV-2 S is used to infect Vero cells (See page 21, paragraph 3) and the infection is inhibited by the antisera (See Fig. S2, page 15 and below), where there is a control sera as well.
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Accordingly, Dieterle et al. teaches each and every aspect of the claims 1-3, 5-6, 14, 19-22, 24-25, 33, 38, 62 and 79.
Claims 1-3, 5-6, 14, 19-22, 24-25, 33, 38, 62 and 79 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Case et al. (bioRxiv preprint doi: https://doi.org/10.1101/2020.05.18.102038; this version posted May 18, 2020.).
The base claim 1 is directed to a recombinant vesicular stomatitis virus (VSV) vector comprising a nucleic acid encoding spike glycoprotein S of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), or biologically active fragment.
The base claim 20 is directed to a recombinant vesicular stomatitis virus (VSV) comprising a genome which comprises a nucleic acid encoding spike glycoprotein S of SARS-CoV-2, or biologically active fragment.
Case et al. teaches the base claims 1 and 20 by stating BSRT7/5 cells were infected with vaccinia virus vTF7-3, transfected with plasmids allowing T7-driven expression of VSV N, P, L, and G, and an infectious molecular cDNA of VSV-SARS-CoV-2-SAA to produce replication competent VSV-SARS-CoV-2-SAA, (See page 15, paragraph 3; page 17, paragraph 1; Page 13, paragraph 1 and Figure 1A-Case et al. below), which also teaches the claims 14 for the eGFP, claim 19 for a VSV particles generated from the VSV vector, and claims 33-34 for replacing the VSV G protein with the SARS-COV-2 spike protein. Case et al. also discloses that the S gene of SARS-CoV-2 isolate Wuhan-Hu-1 (GenBank MN908947.3) was synthesized in two and inserted into an infectious molecular clone of VSV (Whelan et al., 1995) as previously (Carette et al., 2011; Jae et al., 2014). Modifications to the cytoplasmic tail were assembled identically. Other plasmids were previously described: VSV N, P, L and G expression plasmids (Stanifer et al., 2011; Whelan et al., 1995) (See page 17,
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paragraph 1).
Regarding claims 2-3 and 21-22, Case et al. teaches using wild-type S gene of SARS-CoV-2 (GenBank MN908947.3) to insert to VSV plasmid (See page 17, paragraph 1), where the spike protein encoded by the MN908947.3, QHD43416.1, is identical to the SEQ ID NO: 1 (See Table 1 below).
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Regarding claims 5-6 and 24-25 Case et al. teaches that modifications to the cytoplasmic tail were assembled identically to make the constructs as: VSV-SARS-CoV-2-SΔ21 and VSV-SARS-CoV-2-SAA (See Figure 1A-Case et al. above), where the C1253 is deleted in the construct VSV-SARS-CoV-2-SΔ21, which is a mutation of C1253 as claimed in claim 6-(a) and claim 25-(a). Also, the mutant SAA is capable of facilitating replication of VSV-SARS-CoV-2-SAA (See page 15, paragraph 3) that teaches claim 6-(c) and claim 25-(c).
Regarding claim 62, Case et al. teaches the neutralization of VSV-SARS-CoV-2-SΔ21 and SARS-CoV-2 by human antibodies that include tested a subset of these mAbs (304, 306, 309, and 315) for their ability to inhibit VSV-SARS-CoV-2-SΔ21 and SARS-CoV-2 infections on Vero E6 cells (See page 7, paragraph 3 and Fig. 3-A-B and below Figure 3A-Case et al.), which teaches contacting cells (infection) and antibodies (agent) reducing the VSV-SARS-CoV-2-SΔ21 infection to demonstrate that the antibody can precent/treat SARS-COV-2 infection.
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Regarding claim 79, Case et al. teaches that neutralization of VSV-SARS-CoV-2-SΔ21 and SARS-CoV-2 by human immune serum. They obtained 42 serum samples from 20 individuals at different time points after the onset of COVID-19 symptoms (Table 1), tested each sample for neutralization of VSV-SARS-CoV-2-SΔ21 and SARS-CoV-2 on Vero E6 cells and observed that sera with ELISA negative or indeterminate results generally showed low inhibitory titers (EC50 <1/100) (See page 8, paragraph 3), where the control level is the ELISA IgG pre-screening data and the contacting (infecting) cell is Vero E6 and the EC50 is a determining factor by calculation and the result in Table 1 (See page 26) showing the level of the subject being exposure to the
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SARS-COV-2.
Accordingly, Case et al. teaches each and every aspect of the claims 1-3, 5-6, 14, 19-22, 24-25, 33, 38, 62 and 79.
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 50-56 are rejected under 35 U.S.C. 103 as being unpatentable over Case et al. (bioRxiv preprint doi: https://doi.org/10.1101/2020.05.18.102038; this version posted May 18, 2020.) as applied to claims 1-3, 5-6, 14, 19-22, 24-25, 33, 38, 62 and 79 above.
Claims 50 and 56 require an immunogenic composition, a kit, or a device comprising the recombinant VSV.
Case et al. teaches a recombinant VSV/vector expressing the SARS-CoV-2 S protein that can be incorporated into infectious VSV particles to infect cells and can be neutralized by the human antibodies and Human immune serum. However. Case et al. does not explicitly point out a composition, a kit or device.
However, the concept of packaging components into a kit/device/composition is well known and routine in the art. For example, Case et al. discloses a detailed method for generating the VSV-SARS-CoV-2-S construct, and applying it for infecting cells, testing for anti-S or anti-RBD antibodies and performing neutralization assay. It would have been obvious to one of ordinary skill in the art at the time the invention was made to package components into a kit. One would be motivated to do this for commercial exploitation of the invention by providing convenience for the end user. Thus, the claimed invention is obvious over Case’s research. According to MPEP § 2112.01(III), “Where the only difference between a prior art product and a claimed product is printed matter that is not functionally related to the product, the content of the printed matter will not distinguish the claimed product from the prior art. In re Ngai, ** > 367 F.3d 1336, 1339, 70 USPQ2d 1862, 1864 (Fed. Cir. 2004) < (Claim at issue was a kit requiring instructions and a buffer agent. The Federal Circuit held that the claim was anticipated by a prior art reference that taught a kit that included instructions and a buffer agent, even though the content of the instructions differed.). See also In re Gulack, 703 F.2d 1381, 1385-86, 217 USPQ 401, 404 (Fed. Cir. 1983) (“Where the printed matter is not functionally related to the substrate, the printed matter will not distinguish the invention from the prior art in terms of patentability….[T]he critical question is whether there exists any new and unobvious functional relationship between the printed matter and the substrate." ).”
Claims 87-88 are rejected under 35 U.S.C. 103 as being unpatentable over Case et al. (bioRxiv preprint doi: https://doi.org/10.1101/2020.05.18.102038; this version posted May 18, 2020.) as applied to claims 1-3, 5-6, 14, 19-22, 24-25, 33, 38, 62 and 79 above, and further in view of Yahalom-Ronen et al. (bioRxiv preprint doi: https://doi.org/10.1101/2020.06.18.160655; this version posted June 19, 2020).
Regarding claims 87 and 89, they are directed to a method of preventing and/or treating SARS-CoV-2 infection in a subject comprising administering to the subject a therapeutically effective amount of an immunogenic composition comprising the VSV vector/composition.
Although Case et al. does not explicitly teach the administration of the VSV-SARS-CoV-2-S/SΔ21, Case et al. teaches that VSV-SARS-CoV-2-SΔ21, despite the structural differences of the virion, provides a useful tool for screening antibodies, entry-based antiviral agents, and vaccine responses against SARS2-CoV-2 (See page 11, paragraph 1).
Nevertheless, Yahalom-Ronen et al. teaches claim 87 by disclosing injecting/administrating therapeutically effective amount of rVSV-ΔG-spike, in which the glycoprotein of VSV was replaced by the spike protein of the SARS-CoV-2, into golden Syrian hamsters that induces antibodies that effectively bind and neutralize the infectious SARS-CoV-2 virus (See page 11; page 12, paragraph 3), where the subject is a mammal (e.g., a rodent) as claimed in claim 88.
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 Case and Yahalom-Ronen to arrive at an invention as claimed. One of skill in the art would have been motivated to introduce the administering regimen of Yahalom-Ronen into Case’s study because Yahalom-Ronen discloses that a single dose of recombinant VSV-ΔG-spike vaccine provides protection against SARS-CoV-2 challenge (See e.g., Title), and there would be a reasonable expectation of success to develop a method of preventing and/or treating SARS-CoV-2 infection in a subject comprising administering the VSV-ΔG-spike of Yahalom-Ronen and VSV-eGFP-SARS-CoV-2-S of Case.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RUIXUE WANG whose telephone number is (571)272-7960. The examiner can normally be reached Monday-Friday 8:00 am..
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/RUIXUE WANG/Examiner, Art Unit 1672
/NICOLE KINSEY WHITE/Primary Examiner, Art Unit 1672