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
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office Action has been withdrawn pursuant to 37 CFR 1.114.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 October 13, 2025 has been entered.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
This action is in response to the papers filed on October 13, 2025. Claims 1, 3 – 8, 11 – 13, 20, 27, 114 -119, 121 - 123 are currently pending. Claims 1, 3, 4, and 119 have been amended in the Applicant’s amendment filed 29 April, 2025. Claim 120 has been canceled, and claims 121 – 123 have been added in the Applicant’s amendment filed 13 October, 2025.
Applicant's election without traverse of Group I, claims 1 – 8, 11 – 13, 20, 27 – 28, directed to a nucleic acid comprising a nucleotide sequence encoding a VLP; and the election of Species without traverse as follows was previously acknowledged:
Species (A): wherein the lentiviral gag protein is a human immnunodeficiency virus gag polyprotein (instant claim 5)
Species (B): wherein the retroviral gag polyprotein is a lentiviral gag polyprotein (instant claim 4)
Species (C): wherein the therapeutic polypeptide is a CRISPR/Cas effector polypeptide (instant claim 12),
Species (C-a): wherein the polypeptide is a type II CRISPR/Cas effector polypeptide (instant claim 13);
Species (D): wherein the site comprises an amino acid sequence selected from the group consisting of…..Seq ID NO: 890 (instant claim 28), in the reply filed November 21, 2024.
Claims 2, 6, 7, 8, 11 and 20, 114, 115, 117, and 118 (claim 2 now canceled) were previously withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected species, there being no allowable generic or linking claim.
The restriction requirement was previously made FINAL. Note that election of the invention was made without traverse.
Therefore, claims 1, 3 – 5, 12 – 13, 27, 116, 119, and 121 - -123 are under consideration to which the following grounds of rejection are applicable.
Please Note: The examiner acknowledges receiving the Declaration under 37 C.F.R. § 1.132 filed on October 13, 2025 and executed by Dr. Jennifer R. Hamilton.
Priority
The present application filed May 21, 2021, is a 35 U.S.C. 371 national stage filing of International Application No. PCT/US19/61778, filed November 15, 2019, which claims the benefit of Provisional Application 62/889,867, filed August 21, 2019, which claims the benefit of Provisional Application 62/843,139, filed May 3, 2019, which claims the benefit of Provisional Application 62/768,508, filed November 16, 2018.
Thus, the earliest possible priority for the instant application is November 16, 2018.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on October 13, 2025. has been considered. An initialed copy of the IDS accompanies this Office Action.
Withdrawn Objections/Rejections
Claim Rejection - 35 USC § 112(b)
The rejection of claims 1, 3 – 5, 12 – 13, 27, 116, and 119 is withdrawn 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.
The claims have been amended to no longer be indefinite.
In view of the withdrawn rejection, Applicant’s arguments are moot.
Claim Rejection - 35 USC § 103
The rejection of claims 1, 3 – 5, 12 – 13, 27, 116, and 119 under 35 U.S.C. 103 as being unpatentable over Ohlmann et al. (hereinafter referred to as “Ohlmann”) (WO2017068077, published April 27, 2017), as applied to claims 1, 3 – 5, 12 – 13, 27, and 116 above, and further in view of Hübner W. et al.. (hereinafter referred to as “Hubner”) (Hübner W. et al. Sequence of human immunodeficiency virus type 1 (HIV-1) Gag localization and oligomerization monitored with live confocal imaging of a replication-competent, fluorescently tagged HIV-1. J Virol. 2007 Nov;81(22):12596-607. Doi: 10.1128/JVI.01088-07. Epub 2007 Aug 29. PMID: 17728233; PMCID: PMC2168995.) is withdrawn.
The Applicant has convinced the Examiner that there is no advantageous reason one of ordinary skill in the art would combine Ohlmann and Hubner. Ohlmann teaches a HIV based system, comprising a cleavage site, and thus, one of ordinary skill in the art, would not replace this cleavage site with the cleavage site as taught by Hubner. Additionally, the Applicant has filed a Declaration teaching the same.
In view of the withdrawn rejection, Applicant’s argument is moot.
New Objections/Rejections
Claim Rejection - 35 USC § 103
Claims 1, 3 – 5, 12 – 13, 27, 116, 119, and 122 - 123 are rejected under 35 U.S.C. 103 as being unpatentable over Ohlmann et al. (hereinafter referred to as “Ohlmann”) (WO2017068077, published April 27, 2017), and further in view of Luo et al. (hereinafter referred to as “Luo”) (US 20180200188 A1, published July 19, 2018). This is a new rejection necessitated by the response filed October 13, 2025.
Regarding claims 1, 119, and 122-123, Ohlmann teaches gene targeting by methods using viral-derived vector systems related to Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and components thereof (pg. 1, lines 5 – 7). Ohlmann teaches that the GAG-Cas9 vector consists of the fusion of the MLV-GAG polyprotein with the codon-optimized Cas9 sequence from Streptococcus pyogenes (pg. 6, lines 16 – 17) (interpreted as a retroviral GAG protein and a therapeutic peptide, instant claim 1). Ohlmann teaches a HIV-1 GAG-Cas9 vector, wherein the GAG comprises a MA, CA, and NC (Fig. 14A) (interpreted as a retroviral gag protein comprising a MA protein, a CA protein, and a NC polypeptide, and a therapeutic polypeptide). Ohlmann teaches the fusion protein comprises a proteolysis cleavage site located between the viral structural protein moiety and the Cas protein moiety, typically between the Gag protein moiety and the Cas9 protein moiety (pg. 29, lines 10 – 12) (interpreted as one or more heterologous protease cleavage sites and a CRISPR/Cas polypeptide, instant claims 1, 119, and 123). Ohlmann teaches Fig. 1B, wherein fusion polypeptide comprises, in N-terminal to C-terminal order, MA-CA-NC-Cas 9.
Ohlmann does not specifically exemplify that one of the heterologous protease cleavage site comprises Seq ID NO. 882 (claims 1, 119, and 122-123).
Regarding claims 1, 119, and 122-123, Luo teaches a purified or isolated peptide consisting of the amino acid sequence as set forth in any one of SEQ ID NO: 1 that can be used for eliciting an immune response against HIV-1 (Claims 1 and 7) (Please Note: Seq ID No: 1 is 100% identical to instant Seq ID No. 882). Luo teaches this highly conserved HIV-1 protease cleavage site of Seq ID No. 1, such that immune responses against these cleavage sites (“immune response to the 12 protease cleavage sites.” e.g, SEQ ID NOS: 1-12) are advantageous (Paragraph [0030], abstract, para [0007]). Luo teaches that when an immune response is elicited against this cleavage site, the host immune response may destroy the virus before it can establish itself permanently in the host, and immune response that generate unwanted inflammatory responses are avoided (Paragraph [0030]). Luo teaches that the nucleic acid may be inserted into an expression system (Paragraph [0052]).
In view of the benefits of generating an immune response against an HIV cleavage site of SEQ ID NO: 1 as taught by Luo, it would have been prima facia obvious for one of ordinary skill in the art to modify the GAG-Cas9 vector, which comprise the protease cleavage site, SSLYPALTP, as taught by Ohlmann, with the HIV-1 protease cleavage site, SQNYPIVQ (Seq ID No. 1) as taught by Luo, with a reasonable expectation of success in creating a vector that will cleave HIV in the target cell and generate an immune reaction against HIV. It would have been prima facia obvious to combine the cited sources because Ohlmann teaches the GAG-Cas vector, that comprises the GAG protein for the HIV-1, which is composed of the MA and CA regions, and the protease cleavage site, but does not teach this HIV-1 specific protease cleavage site; and Hubner teaches the HIV-1 protease cleavage site that can be inserted into a vector, and teaches that this cleavage site can destroy the virus before it can be established permanently in the host, and unwanted inflammatory responses are avoided.
Regarding claim 4, the combined teachings of Ohlmann and Hubner render obvious claim 1. Moreover, Ohlmann teaches the host range of retroviral vectors includes lentiviral vectors (pg. 21, line 15) (referring to instant claim 4).
Regarding claim 5, the combined teachings of Ohlmann and Hubner render obvious claim 1. Moreover, Ohlmann teaches a HIV-1 GAG-Cas9 vector, wherein the GAG comprises a MA, CA, and NC (Fig. 14A).
Regarding claims 12, 13, and 116, the combined teachings of Ohlmann and Hubner render obvious claim 1. Moreover, Ohlamann teaches that the Cas protein can be a type II Cas protein, specifically a Cas9 protein (pg. 26, line 23 and pg. 27, lines 4 - 5).
Regarding claim 27, the combine teachings of Ohlmann and Hubner render obvious claim 1. Moreover, Ohlmann teaches the GAG-Cas9 amino acid sequence (Seq ID No. 22), which comprises the amino acids “PKKKRKV” (referring to the nuclear localization sequence, instant claim 27). (Please Note: “PKKKRKV” is a 100% identical to the NLS sequence with Seq ID No. 909, as taught in paragraph [0442] of the as-Filed Specification).
Please Note: Claim 121 is free of art.
Conclusion
Claims 1, 3 – 8, 11 – 13, 20, 27, 114 -119, and 122 remain rejected.
Claim 121 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to VYOMA SHAILESH THAKKER whose telephone number is (571)272-2954. The examiner can normally be reached M-F 8:30 - 5:30 EST.
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/VYOMA SHUBHAM TIWARI/Examiner, Art Unit 1634
/MARIA G LEAVITT/ Supervisory Patent Examiner, Art Unit 1634