DETAILED ACTION
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 elections without traverse in response to an Election of Species Requirement in the reply filed on 08/05/2025 is acknowledged, the elections being: a dimeric soluble CD4 comprising SEQ ID NO: 9; a T cell-responsive promoter comprising a CMV promoter; one small RNA targeting Vif, Tat, or CCR5 comprising SEQ ID NO: 62; a therapeutic cargo portion comprising a nucleotide sequence comprising SEQ ID NO: 1.
Claims 1-8 and 10-32 read on the elected invention and are examined on the merits herein.
As SEQ ID NOs: 1 and 9 were found to be allowable over the prior art, the Examiner expanded the search to include the remaining species of dimeric soluble CD4 and therapeutic cargo portion comprising a nucleotide sequence; this expanded search included SEQ ID NOs: 2-8, 10, 76-78, 80-85, 87.
Priority
The instant application is a national stage entry under 35 U.S.C. § 371 of PCT/US2021/020721 (filed 03/03/2021). Acknowledgement is made of Applicants’ claim for benefit of U.S. Provisional Application No. 62/984,716 (filed 03/03/2020).
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-3, 8, 14, 19, and 23-27 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Zeng, et al. (US 2021/0275589).
Zeng, et al. teaches immune cells comprising a chimeric receptor, a chimeric co-receptor, and/or a co-receptor (Abstract).
Regarding claims 1-3, 8, 14, 19: Zeng, et al. teaches an engineered immune cell comprising a chimeric receptor (par. 0013), wherein the chimeric receptor is a chimeric antigen receptor (CAR) (par. 0138). Zeng, et al. further teaches an embodiment wherein the CAR comprises an anti-CCR5 binding moiety (par. 0142, pg. 14), wherein the anti-CCR5 binding moiety comprises siRNA for inactivation of the CCR5 gene (par. 0035). The anti-CCR5 CAR may further comprise a broadly neutralizing antibody (bNAb), such as VRC01 or 3BNC117 (par. 0142, pg. 15). Further disclosed is a vector comprising nucleic acid(s) encoding the chimeric receptor (par. 0197), wherein the vector is a viral vector comprising a CMV promoter (pars. 0200, 0203).
The viral vector comprising nucleic acids encoding the anti-CCR5 CAR further comprising VRC01 or 3BNC117 and a CMV promoter reads on: the viral vector comprising a therapeutic cargo portion, wherein the therapeutic cargo portion comprises a nucleotide sequence that encodes at least one soluble exogenous factor capable of inhibiting HIV infection, and a T cell-responsive promoter that regulates expression of the nucleotide sequence limitation recited in claim 1; the wherein the at least one soluble exogenous factor comprises an anti-HIV antibody limitation recited in claim 2; the wherein the anti-HIV antibody is a VRC01 antibody or a 3BNC117 antibody limitation recited in claim 3; the wherein the T cell-responsive promoter comprises a CMV promoter limitation recited in claim 8; the wherein the therapeutic cargo portion further comprises at least one small RNA that targets CCR5 limitation recited in claim 14; and the wherein the T cell-responsive promoter comprises a CMV promoter limitation recited in claim 19.
Regarding claims 23-27: Following the above discussion, Zeng, et al. teaches the CAR gene controlled by an EF1α promoter in pLVX vectors; 293T cells were transfected with the CAR plasmid, 2nd generation lentiviral packaging plasmid, and a VSV-G envelope coding plasmid (par. 0423). Virus supernatant was harvested at 48h and 72h post-transfection (par. 0423). Pan T cells enriched from a peripheral blood mononuclear cell population were activated for 48h then incubated with the lentivirus before CAR-T cell expansion (par. 0424); anti-CCR5 CAR-T cells were used as effector cells in SHIV infection assays, with CD4 T cells as the target cells (par. 0426). The anti-CCR5 CAR-T cell reads on the modified cell comprising a lymphocyte infected with a lentiviral particle capable of infecting a target cell limitation recited in claim 23, and the VSV-G envelope coding plasmid reads on the envelope protein capable of infecting the lymphocyte limitation recited in claim 23. As the EF1α promoter reads on the T cell responsive promoter limitation recited in claim 1, the CAR gene controlled by an EF1α promoter in pLVX vectors reads on the viral vector of claim 1 limitation recited in claim 23. Additionally, as pan T cell populations necessarily comprise CD4+ T cells, this reads on the modified cell comprising a lymphocyte limitation recited in claim 24, the wherein the lymphocyte comprises a T cell limitation recited in claim 25, the wherein the lymphocyte is a T cell, and wherein the T cell comprises a CD4 T cell limitation recited in claim 26, as well as the wherein the T cell is a CD4 T cell limitation recited in claim 27.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-5, 8, 14, 17-19, and 23-27 are rejected under 35 U.S.C. 103 as being unpatentable over Zeng, et al. (US 2021/0275589) in view of Haim, et al. (PLoS Pathog. 2009), further in view of Falkenhagen, et al. (BMC Biotechnol. 2016).
The teachings of Zeng, et al. are set forth above. Claims 1-3, 8, 14, 19, and 23-27 are anticipated by Zeng, et al.
Haim, et al. teaches soluble forms of CD4 inhibit HIV-1 entry into CD4-expressing cells (Abstract).
Regarding claims 4-5, 17-18: It is set forth above the anti-CCR5 CAR taught by Zeng, et al. (pars. 0035, 0142) anticipates the viral vector of claims 1 and 14. Zeng, et al. does not teach the therapeutic cargo portion of the viral vector as comprising a soluble CD4 protein or fragment thereof.
However, Haim, et al. teaches a four-domain soluble CD4 (sCD4) expressed in 293 cells after transfection (pg. 2; col. 2, par. 2); this reads on the wherein the at least one soluble exogenous factor comprises a soluble CD4 protein or a fragment thereof limitation recited in claim 4, the wherein the soluble CD4 or a fragment thereof comprises a dimeric soluble CD4 limitation recited in claim 5, the wherein the at least one soluble exogenous factor comprises a soluble CD4 protein or a fragment thereof limitation recited in claim 17, and the wherein the soluble CD4 or a fragment thereof comprises a dimeric soluble CD4 limitation recited in claim 18.
It would have been prima facie obvious to a person having ordinary skill in the art to have modified the viral vector taught by Zeng, et al. by including the sCD4 taught by Haim, et al. This conclusion of obviousness is based on the ‘teaching, suggestion, or motivation rationale’. Haim, et al. teaches after engagement of sCD4, HIV-1 undergoes a transient phase of activation, during which attachment to cells expressing CCR5 allows entry to occur; but this activated state is short-lived and followed by seemingly irreversible structural rearrangements and loss of infectivity (pg. 7; cols. 1-2, par. 1). Therefore, a person having ordinary skill in the art would have been motivated to include the sCD4 as taught by Haim, et al. in the anti-CCR5 viral vector taught by Zeng, et al., for the loss of infectivity taught by Haim, et al. Further, as Falkenhagen, et al. teaches sCD4 cloned into a lentiviral vector to generate pLV-CMV-sCD4 (pg. 2; col. 2, par. 4), a person having ordinary skill in the art would have more than a reasonable expectation of success in modifying the viral vector to include sCD4.
Thus, the limitations of claims 4-5 and 17-18 are rendered obvious.
Claims 1-3, 8, 10-11, 14, 19-20, and 23-27 are rejected under 35 U.S.C. 103 as being unpatentable over Zeng, et al. (US 2021/0275589), in view of Raikur, et al. (Oncoimmunology. 2018), and Zhang, et al. (J Gene Med. 2005).
The teachings of Zeng, et al. are set forth above. Claims 1-3, 8, 14, 19, and 23-27 are anticipated by Zeng, et al.
Raikur, et al. teaches anti-CD5 antigen binding domains in NK and CRISPR-edited T cell lines (Title). Zhang, et al. teaches modifications in the basic and/or hydrophobic domains of the IL-2 signal peptide (Abstract).
Regarding claims 10-11, 20: It is set forth above the anti-CCR5 CAR taught by Zeng, et al. (pars. 0035, 0142) anticipates the viral vector of claims 1 and 14. Zeng, et al. does not teach the therapeutic cargo portion of the viral vector as comprising a secretory signal operably linked to the nucleotide sequence that encodes the soluble exogenous factor.
However, Raikur, et al. teaches CARs comprising an interleukin-2 (IL-2) signal peptide (pg. 2; Fig. 1 description); this reads on the wherein the therapeutic cargo portion further comprises a secretory signal operably linked to the nucleotide sequence that encodes the soluble exogenous factor limitation recited in claim 10, the wherein the secretory signal comprises an IL-2 secretory signal limitation recited in claim 11, and the wherein the therapeutic cargo portion further comprises a secretory signal operably linked to the nucleotide sequence that encodes the soluble exogenous factor limitation recited in claim 20.
It would have been prima facie obvious to a person having ordinary skill in the art to have modified the anti-CCR5 CAR taught by Zeng, et al. by including the IL-2 signal peptide taught by Raikur, et al. This conclusion of obviousness is based on the ‘teaching, suggestion, or motivation rationale’. Zhang, et al. teaches a modified IL-2 signal peptide augments protein secretion both in vitro and in vivo (Abstract: Conclusions); further, as evidenced by both Zhang, et al. and Raikur, et al., the use of IL-2 as a signal peptide is well-known in the art. Therefore, a person having ordinary skill in the art would have more than a reasonable expectation of success in modifying the anti-CCR5 CAR of Zeng, et al. by including a secretory signal sequence encoding for an IL-2 signal peptide.
Thus, the limitations of claims 10-11 and 20 are rendered obvious.
Claims 1-3, 8, 14-16, 19, and 21-27 are rejected under 35 U.S.C. 103 as being unpatentable over Zeng, et al. (US 2021/0275589), in view of Pauza, et al. (US 2018/0010147).
The teachings of Zeng, et al. are set forth above. Claims 1-3, 8, 14, 19, and 23-27 are anticipated by Zeng, et al.
Pauza, et al. teaches immunization and immunotherapy for the treatment or prevention of HIV (Abstract).
Regarding claims 15-16, 21-22: It is set forth above the anti-CCR5 CAR taught by Zeng, et al. (pars. 0035, 0142) anticipates the viral vector of claim 14. Zeng, et al. does not teach the one small RNA as comprising either SEQ ID NOs: 62 or 65, nor having at least 80% sequence identity thereto, as required by the limitations recited in the instant claims.
However, Pauza, et al. teaches a viral delivery system including a lentiviral particle containing a small RNA capable of inhibiting CCR5, wherein the small RNA comprises a microRNA cluster (par. 0090); further disclosed is an embodiment wherein the microRNA cluster comprises SEQ ID NO: 31 (par. 0093). As SEQ ID NO: 31 shares 100% sequence identity with instant SEQ ID NOs: 62 and 65, this reads on the wherein the at least one small RNA comprises a sequence having at least 80% sequence identity to SEQ ID NO: 62 limitation recited in claim 15, the wherein the at least one small RNA comprises SEQ ID NO: 62 limitation recited in claim 16, the wherein the at least one small RNA comprises a sequence having at least 80% sequence identity to SEQ ID NO: 65 limitation recited in claim 21, and the wherein the at least one small RNA comprises SEQ ID NO: 65 limitation recited in claim 22. See end of Office action for sequence alignments.
It would have been prima facie obvious to a person having ordinary skill in the art to have modified the anti-CCR5 CAR taught by Zeng, et al. by substituting the siRNA against CCR5 with the microRNA cluster against CCR5 encoded by SEQ ID NO: 31, as taught by Pauza, et al. This conclusion of obviousness is based on the ‘substitution rationale’; the use of the microRNA cluster in place of the siRNA is a predictable use of prior art elements according to their established functions of inhibiting gene expression, leading to the predictable result of inhibition of CCR5. This rationale aligns with the principle of a simple substitution of one known element for another to obtain predictable results; see MPEP 2143(I)(B).
Thus, the limitations recited in claims 15-16 and 21-22 are rendered obvious.
Claims 28-32 are rejected under 35 U.S.C. 103 as being unpatentable over Pauza, et al. (US 2018/0010147), in view of Zeng, et al. (US 2021/0275589).
The teachings of Pauza, et al. and Zeng, et al. are set forth above.
Regarding claims 28-29: Pauza, et al. teaches a lentiviral vector system for expressing a lentiviral particle, wherein the target of interest is chemokine receptor CCR5; further disclosing an embodiment wherein the system comprises a lentiviral vector, an envelope plasmid, a first helper plasmid for expressing the gag and pol genes, and a second helper plasmid expressing the rev gene (par. 0025). This reads on the viral delivery system comprising at least one helper plasmid comprising nucleotide sequences for expressing a functional protein derived from each of a Gag, Pol, and Rev gene; and an envelope plasmid comprising a DNA sequence for expressing an envelope protein capable of infecting a target cell limitations recited in claim 28, as well as the wherein the at least one helper plasmid comprises first and second helper plasmids, wherein the first helper plasmid encodes nucleotide sequences for expressing functional proteins derived from the Gag and the Pol genes, and the second helper plasmid encodes a nucleotide sequence for expressing a protein derived from the rev gene limitations recited in claim 29.
Pauza, et al. does not teach the lentiviral vector as the viral vector of claim 1, as required by the remaining limitations of the instant claims. However, it is set forth above Zeng, et al. teaches a lentiviral vector comprising an anti-CCR5 CAR that anticipates the viral vector of claim 1 (pars. 0035, 0142).
It would have been prima facie obvious to a person having ordinary skill in the art to have modified the lentiviral vector system of Pauza, et al. by substituting the lentiviral vector wherein the target of interest is CCR5 with the lentiviral vector comprising the anti-CCR5 CAR, as taught by Zeng, et al. This conclusion of obviousness is based on the ‘substitution rationale’; the use of the anti-CCR5 CAR lentiviral vector in place of the lentiviral vector targeting CCR5 is a predictable use of prior art elements according to their established functions of delivering genetic material into a cell, leading to the predictable result of modulating the activity of CCR5 by expressing the lentiviral particle. This rationale aligns with the principle of a simple substitution of one known element for another to obtain predictable results; see MPEP 2143(I)(B).
Thus, the limitations recited in claims 28-29 are rendered obvious.
Regarding claims 30-32: Pauza, et al. teaches a method wherein PBMCs isolated from a subject infected with HIV are contacted with a therapeutically effective amount of a stimulatory agent ex vivo, transduced with a lentiviral particle comprising a small RNA capable of inhibiting CCR5, and cultured from 1 to 35 days (par. 0085); this reads on the method of treating HIV, the method comprising contacting PBMC isolated from a subject with a therapeutically effective amount of a stimulatory agent, wherein the contacting is carried out ex vivo; transducing the PBMC ex vivo with a lentiviral particle comprising an envelope protein capable of infecting the PBMC, and culturing the transduced PBMC for at least 1 day limitations recited in claim 30. Pauza, et al. further teaches infusing the transduced PBMC into the subject (par. 0085); this reads on the limitations recited in claim 31. Additionally, Pauza, et al. teaches the stimulatory agent comprises a gag peptide or HIV vaccine (par. 0085); this reads on the limitations recited in claim 32.
Pauza, et al. does not explicitly teach the lentiviral particle as comprising the viral vector of claim 1, as required by the remaining limitations of the instant claims. However, it is set forth above Zeng, et al. teaches a lentiviral particle comprising an anti-CCR5 CAR that anticipates the viral vector of claim 1 (pars. 0035, 0142).
It would have been prima facie obvious to a person having ordinary skill in the art to have modified the method of Pauza, et al. by substituting the lentiviral particle comprising a small RNA capable of inhibiting CCR5 with the lentiviral particle comprising the anti-CCR5 CAR, as taught by Zeng, et al. This conclusion of obviousness is based on the ‘substitution rationale’; the use of the lentiviral particle comprising a small RNA capable of inhibiting CCR5 in place of the lentiviral particle comprising the anti-CCR5 CAR is a predictable use of prior art elements according to their established functions of delivering genetic material into a cell, leading to the predictable result of transducing a population of PBMCs. This rationale aligns with the principle of a simple substitution of one known element for another to obtain predictable results; see MPEP 2143(I)(B).
Thus, the limitations recited in claims 30-32 are rendered obvious.
Nonstatutory Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
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Claims 1-3, 8, 14-16, 19, 21-27, and 30 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of U.S. Patent No. 10,036,038 in view of Zeng, et al. (US 2021/0275589), as evidenced by Boncompain, et al. (Sci Adv. 2019), Scheid, et al. (Nature. 2016), and Qin (PLoS One. 2010).
The teachings of Zeng, et al. are set forth above.
Regarding the instant claims:
The claims of U.S. Patent No. 10,036,038 recite a lentiviral vector comprising small RNA that targets CCR5, as well as compositions and methods of use thereof. Claims 1-3, 8, 14-16, 19, 21-27, and 30 of the instant application differ in the soluble exogenous factor of the lentiviral vector and T cell-responsive promoter only, the soluble exogenous factor of the instant claims being an anti-HIV antibody (e.g., 3BNC117). As inclusion of an anti-HIV antibody 3BNC117 and T cell-responsive promoter would have been prima facie obvious to a person having ordinary skill in the art, the instant claims are thus rejected over the claims of U.S. Patent No. 10,036,038.
The case for obviousness is set forth below, followed by a brief comparison of claims.
U.S. Patent No. 10,036,038 teaches a lentiviral vector, wherein the therapeutic cargo portion comprises small RNA that targets CCR5, i.e., an encoded microRNA cluster comprising patented SEQ ID NO: 31. U.S. Patent No. 10,036,038 does not teach the therapeutic cargo portion as additionally comprising at least one soluble exogenous factor capable of inhibiting HIV infection, as required by the instant claims.
However, Zeng, et al. teaches an anti-CCR5 CAR comprising 3BNC117 and a CMV promoter (pars. 0035, 0142); the 3BNC117 reads on the at least one soluble exogenous factor capable of inhibiting HIV infection limitation while the CMV promoter reads on the T cell-responsive promoter limitation recited in the instant claims.
Regarding the at least one soluble exogenous factor capable of inhibiting HIV infection:
U.S. Patent No. 10,036,038 targets CCR5 by using microRNA to inhibit its expression. As evidenced by Boncompain, et al., HIV-1 entry into cells is initiated by the interaction of its surface envelope glycoprotein, gp120, with two host cell surface receptors: CD4 and a co-receptor; Boncompain, et al. further discloses CCR5 is the principal co-receptor for R5-tropic strains responsible for the transmission and establishment of HIV-1 infection (pg. 1; col. 1, par. 2). As evidenced by Scheid, et al., 3BNC117 is a broad and potent neutralizing antibody against the CD4 binding site of the HIV-1 Env protein (Abstract); 3BNC117 increased autologous antibody responses in HIV-1-infected individuals and enhanced clearance of infected cells in humans and humanized mice (pg. 1; col. 1, par. 2).
It would have been prima facie obvious to a person having ordinary skill in the art to have modified the lentiviral vector of U.S. Patent No. 10,036,038 by including the bNAb 3BNC117, as taught by Zeng, et al. This conclusion of obviousness is based on the ‘combining known alternatives rationale’. The combination of targeting the required initial CD4 receptor (i.e., the 3BNC117 taught by Zeng, et al.) and the principal co-receptor CCR5 as the required second receptor (i.e., the microRNA for inhibition of CCR5 taught by U.S. Patent No. 10,036,038), using methods for delivery of genetic material into a cell well-known in the art (i.e., the lentiviral vector), is a predictable use of known alternatives for inhibiting CD4 and CCR5 expression, leading to the predictable result of expression inhibition. This rationale aligns with the principle of combining known prior art elements according to known methods to yield predictable results; see MPEP 2143(I)(A).
Regarding the T cell-responsive promoter:
It would have been prima facie obvious to a person having ordinary skill in the art to have modified the lentiviral vector of U.S. Patent No. 10,036,038 by including the CMV promoter, as taught by Zeng, et al. This conclusion of obviousness is based on the ‘combining known prior art elements rationale’; the combination of a nucleic acid molecule encoding for a target of interest with a promoter for driving the expression thereof within a lentiviral vector is a predictable use of combining prior art elements for driving expression of the nucleic acid molecule within a cell. As evidenced by Qin, et al., constitutive promoters are used routinely to drive ectopic gene expression, wherein the CMV promoter is a commonly used promoter for mammalian systems (Abstract); thus, a person having ordinary skill in the art would have more than a reasonable expectation of success in incorporating the CMV promoter into the lentiviral vector of U.S. Patent No. 10,036,038. This rationale aligns with the principle of combining known prior art elements according to known methods to yield predictable results; see MPEP 2143(I)(A).
Patented claims 1-3 of U.S. Patent No. 10,036,038 are drawn to SEQ ID NO: 31, which comprises instant SEQ ID NOs: 62 and 65; see end of Office action for sequence alignments. Thus, the modified vector of U.S. Patent No. 10,036,038 set forth above reads on instant claims 1-3, 8, 14-16, 19, and 21-22.
Patented claims 4-5 of U.S. Patent No. 10,036,038 are drawn to a lentiviral particle produced by a packaging cell and capable of infecting a target cell, the lentiviral particle comprising an envelope protein capable of infecting the target cell; and an encoded microRNA cluster encoded by SEQ ID NO: 31; this reads on instant claim 23.
Patented claims 8-11 of U.S. Patent No. 10,036,038 are drawn to a modified cell comprising a primary T cell infected with the lentiviral particle, wherein the modified cell is a primary CD4+ T cell; this reads on instant claims 24-27.
Patented claims 12-18 of U.S. Patent No. 10,036,038 are drawn to a method of treating cells infected with HIV, comprising isolating PBMC from a subject infected with HIV and contacting the PBMC ex vivo with a therapeutically effective amount of a stimulatory agent, transducing the PBMC ex vivo with the lentiviral particle, culturing the transduced PBMC for at least about 1 day; this reads on instant claim 30.
Claim 1 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending Application No. 18/227,775 in view of Zeng, et al. (US 2021/0275589), as evidenced by Boncompain, et al. (Sci Adv. 2019) and Scheid, et al. (Nature. 2016).
The teachings of Zeng, et al., are set forth above.
Regarding claim 1: Claim 1 of copending Application No. 18/227,775 recites a viral vector comprising a therapeutic cargo portion, wherein the therapeutic cargo portion comprises a nucleotide sequence that encodes at least one soluble exogenous factor, and a T cell-responsive promoter that regulates expression of the nucleotide sequence; this reads on the identical limitations recited in instant claim 1. Claim 1 of copending Application No. 18/227,775 does not recite the at least one soluble exogenous factor as capable of inhibiting HIV infection, as required by the remaining limitation recited in instant claim 1.
However, Zeng, et al. teaches an anti-CCR5 CAR comprising 3BNC117 and a CMV promoter (pars. 0035, 0142); the 3BNC117 reads on the at least one soluble exogenous factor capable of inhibiting HIV infection limitation recited in instant claim 1.
As evidenced by Boncompain, et al., HIV-1 infects immune cells, in particular CD4+ T cells, via cell-cell interactions between its surface envelope glycoprotein gp120 with two host cell surface receptors: CD4 and a coreceptor (pg. 1; col. 1, par. 2). As evidenced by Scheid, et al., 3BNC117 is a broad and potent neutralizing antibody against the CD4 binding site of the HIV-1 Env protein (Abstract); 3BNC117 increased autologous antibody responses in HIV-1-infected individuals and enhanced clearance of infected cells in humans and humanized mice (pg. 1; col. 1, par. 2).
Therefore, it would have been prima facie obvious to a person having ordinary skill in the art to have modified the viral vector of copending claim 1 of Application No. 18/227,775 by including the bNAb 3BNC117, as taught by Zeng, et al. This conclusion of obviousness is based on the ‘teaching, suggestion, or motivation rationale’; one would have been motivated to include 3BNC117 for the reasons disclosed by Boncompain, et al., namely to inhibit HIV-1 from infecting CD4+ T cells. Further, as Zeng, et al. teaches a viral vector comprising bNAb 3BNC117 and a T cell-responsive promoter, one skilled in the art would have more than a reasonable expectation of success.
Thus, the limitations of instant claim 1 are rendered obvious by copending Application No. 18/227,775 in view of Zeng, et al.
This is a provisional nonstatutory double patenting rejection.
Claims 30-32 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 8 of U.S. Patent No. 11,980,663 and claims 1 and 4 of copending Application No. 18/227,768, each in view of Zeng, et al. (US 2021/0275589), and as evidenced by Boncompain, et al. (Sci Adv. 2019) and Scheid, et al. (Nature. 2016).
The teachings of Zeng, et al. are set forth above.
Regarding claims 30-32: Claim 1 of U.S. Patent No. 11,980,663 recites a method of treating HIV in a HIV+ subject, comprising:
immunizing a subject with a therapeutically effective amount of an HIV vaccine;
purifying PBMC obtained from the subject;
contacting the PBMC ex vivo with a therapeutically effective amount of an HIV vaccine;
transducing the PBMC ex vivo with a viral delivery system that comprises a microRNA cluster encoding:
(i) at least one microRNA capable of inhibiting the production of chemokine receptor CCR5 and at least one microRNA capable of inhibiting the production of HIV tat gene,
(ii) at least one microRNA capable of inhibiting the production of HIV tat gene and at least one microRNA capable of inhibiting the production of HIV vif gene or
(iii) at least one microRNA capable of inhibiting the production of chemokine receptor CCR5, at least one microRNA capable of inhibiting the production of HIV tat gene and at least one microRNA capable of inhibiting the production of HIV vif gene;
culturing the transduced PBMC for about 1 to about 35 days; and
infusing the transduced PBMC into the subject,
wherein the subject receives a cyclophosphamide pre-treatment prior to infusing the transduced PBMC.
Copending claims 1 and 4 of U.S. Application No. 18/227,768 recite the same steps outlined above.
It is set forth above the viral vector of the instant application is rendered obvious over U.S. Patent No. 10,036,038 in view of Zeng, et al. For the same reasons, the method of patented claim 1 of U.S. Patent No. 11,980,663 and the method of copending claims 1 and 4 of U.S. Application No. 18/227,768 likewise renders obvious instant claims 30-32.
Allowable Subject Matter
Claims 6-7 and 12-13 are allowed. SEQ ID NOs: 1-10, 76-78, 80-85, 87 are free of the prior art.
Conclusion
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/GINA PRONZATI/Examiner, Art Unit 1633
/ALLISON M FOX/Primary Examiner, Art Unit 1633
SEQUENCE ALIGNMENTS
Query (instant SEQ ID NO: 62) vs. Subject (Pauza, et al.; patented SEQ ID NO: 31)
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189
597
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Query (instant SEQ ID NO: 65) vs. Subject (Pauza, et al.; patented SEQ ID NO: 31)
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400
591
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