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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 01/30/2026 has been entered.
Status of the Claims
Claims 16 and 18-28 are currently pending.
Claims 26, 27 and 28 have been withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species and Invention, there being no allowable generic or linking claim.
Claims 1-15, 17, and 29-32 are cancelled.
Claims 16 and 18-25 have been considered on the merits.
Withdrawn Rejections
The 103 rejection made onto claims 16 and 18-25 have been withdrawn in light of the Remarks submitted on 01/30/2026.
New Rejections
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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 16 and 18-22 are rejected under 35 U.S.C. 103 as being unpatentable over Heidmann et al (WO2004087748A1), in view of Gagnepain (Thesis Dissertation, “Evaluation of new lentiviral vector pseudotypes for gene transfer into hematopoietic cells”, 2014), and Lavillette et al (J. of Virology, 2002).
Regarding claim 16, Heidmann teaches a method of obtaining cells which have been infected with stable lentiviral particles pseudotyped with HERV-FRD (a.k.a. syncytin-2) and HERV-W (a.k.a. syncytin- 1) (pg. 42, last para spanning pg. 43). Additionally, Heidmann teaches a “eukaryotic expression vector according to the invention is particularly useful for gene therapy in particular to compensate for disorders resulting in an absence of expression of a lower than normal expression of fusogenic proteins, such as syncytin 2” as required by claim 16, 21, and 22 (pg. 7, para 5). Heidmann teaches that the lentiviral particle is packaged with the Syncytin gene of interest (pg. 45, last para). Heidmann teaches that it can be clearly observed that the HERV-FRD envelope confers infectivity to the virions when expressed in lentiviral particles, which meets the limitations of claim 16 “which have high physical and/or infectious titer(s)” (pg. 45 last para spanning pg. 46).
Regarding claim 18, Heidmann teaches that the method is completed in vitro by contacting cells with the lentiviral particles (Example 2, pg. 34-35).
Regarding claim 19, Heidmann teaches a method of obtaining cells which have been infected with stable lentiviral particles pseudotyped with HERV-FRD (a.k.a. syncytin-2) and HERV-W (a.k.a. syncytin- 1) (pg. 42, last para spanning pg. 43).
Regarding claims 21 and 22, Heidmann teaches a “eukaryotic expression vector according to the invention is particularly useful for gene therapy in particular to compensate for disorders resulting in an absence of expression of a lower than normal expression of fusogenic proteins, such as syncytin 2” (pg. 7, para 5).
Heidmann teaches the titer to range from 1.9 x 101 – 3.6 x 102 CFU/mL. however the requisite information to translate the CFU/ml unit to the claimed TU/ml or ng p24/ml units is not provided by Heidmann, therefore Gagnepain is relied upon below to teach the titer employing comparable units as required by claim 20.
Additionally, Heidmann does not teach that the method is completed on B cells as required by claim 16.
However, Gagnepain teaches a method of pseudo-typing lentiviral vectors with baboon endogenous retrovirus (BaEV; see pgs 239-240) and successfully transducing human quiescent B cells (pg. 242, para 2), BCR stimulated B cells (pg. 242, para 3), and memory B cells (pg. 243, last para). Additionally, Gagnepain teaches that VSV-G-LVs are sensitive to the human complement system that restricts its use in vivo in humans however, the BaEV pseudotyped lentiviral vectors (BaEV-LVs) are resistant to the human complement system which means that “BaEV-LVs could survive in human because we have not developed immune respons against the baboon endogenous retrovirus” (pg. 255, para 2). Gagnepain teaches the pseudotyping of lentiviral vectors for specific use in B cells or hematopoietic cells with various envelope glycoproteins including GALV, RD114, Measles virus, VSV-G, and BaEV (Table 1, pg. 40-41; and Fig. 24 pg. 245). Gagnepain teaches that BaEV-LVs can be produced at significantly higher titers such as 5 x 107 as required by claim 20 (pg. 253, para 2-3).
Although Gagnepain does not disclose the use of endogenous retroviral syncytins in B cells, Lavillette et al teaches the similarities between HERVs, BaEV, and other retroviruses. Lavillette teaches that phylogenetic analysis of HERV-W (syncytin-1) envelope glycoprotein suggested that it shares some relation to a wildly dispersed interference group of retroviruses that includes RD114 and BaEV, among others (pg. 6443, col. 1, para 2). Lavillette teaches that this group of retroviruses all share the use of human sodium-dependent neutral amino acid transporter type 2 (hASCT2), however both HERV-W and BaEV can also use ASCT1, whereas the other retroviruses presented cannot use ASCT1 (pg. 6443, col. 1, para 2-3). Additionally, Lavillette teaches that the HERV-W envelope can be used to pseudotype lentiviral vectors to form infectious virions able to transduce CD4-negative human cells (pg. 6443, col. 1, para 2). Therefore, Lavillette supports that both BaEV and HERV-W both act on hASCT1 and hASCT2 receptors.
One of ordinary skill in the art would find it obvious at the effective filling date to combine the ERV syncytin pseudotyped lentiviral particles of Heidmann with the B cells of Gagnepain based on the teachings of both Gagnepain and Lavillette to arrive at the instant invention. Taken together, Heidmann teaches the method of pseudotyping lentiviral vectors with ERV syncytins, and Gagnepain and Lavillette, provide a reasonable expectation that one of ordinary skill in the art would find the method of infecting B cells with a lentiviral particle pseudotyped with an ERV syncytin, such as HERV-W, obvious to try from a finite number of endogenous retroviral envelope glycoproteins. Additionally, one would have an expectation of success in this combination because Gagnepain teaches successful B cell transduction in multiple B cells of different states employing BaEV-LV and Lavillette teaches the human receptor similarities specifically between HERV-W and BaEV.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the effective time of filing of the invention, especially in the absence of evidence to the contrary.
Claims 16 and 23 is rejected under 35 U.S.C. 103 as being unpatentable over Heidmann et al (WO2004087748A1), in view of Gagnepain (Thesis Dissertation, “Evaluation of new lentiviral vector pseudotypes for gene transfer into hematopoietic cells”, 2014), and Lavillette et al (J. of Virology, 2002), as applied to claims 16 and 18-22 above, and in further view of Frecha et al (Advances in the Field of Lentivector-based Transduction of T and B Lymphocytes for Gene Therapy, 2010).
With regards to claim 23, Heidmann, Gagnepain, and Lavillette teach the limitations of the independent claim 16 above.
Heidmann, Gagnepain, and Lavillette do not teach that the therapeutic gene of interest codes for an immunoglobulin as required by claim 23.
However, Frecha teaches about the expression of transgenes in B cells. Frecha teaches that “transgene expression in B cells is of particular interest as B cells have the potential to induce specific immune activation and tolerance, which could improve genetic vaccination against cancer or autoimmune diseases” (pg. 1749, col 2, para 2).
Additionally, Frecha teaches about a B-cell therapy for AIDS which involves a lentiviral particle encoding for anti-HIV antibodies as required by claims 16 and 23 (Table 2). Frecha teaches that “LVs were used to introduce an anti-HIV antibody coding regions into hematopoietic stem cells and differentiation of the transduced cells into antibody-secreting autologous B cells was achieved with success. Alternatively, lentiviral transduction and reinfusion of autologous B cells would allow a quick and continuous supply of HIV-neutralizing antibodies in vivo” (pg. 1750, col 1, para 1).
One of ordinary skill in the art would find it obvious at the effective filling date of the instant invention to combine the endogenous retroviral syncytin pseudotyped lentiviral transduction method taught by Heidmann, Gagnepain, and Lavillette with the B cells modified to express a gene of interest, more particularly an immunoglobulin/antibody taught by Frecha to arrive at the instant invention. One of ordinary skill in the art would be motivated to make this combination because Frecha teaches that “transgene expression in B cells is of particular interest as B cells have the potential to induce specific immune activation and tolerance, which could improve genetic vaccination against cancer or autoimmune diseases” (pg. 1749, col 2, para 2) and because Frecha teaches “lentiviral transduction and reinfusion of autologous B cells would allow a quick and continuous supply of HIV-neutralizing antibodies in vivo” (pg. 1750, col 1, para 1). One of ordinary skill in the art would have a reasonable expectation of success when combining Heidmann, Gagnepain, and Lavillette with Frecha because Frecha teaches that “LVs were used to introduce an anti-HIV antibody coding regions into hematopoietic stem cells and differentiation of the transduced cells into antibody-secreting autologous B cells was achieved with success” (pg. 1750, col 1, para 1).
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the effective time of filing of the invention, especially in the absence of evidence to the contrary.
Claims 16 and 24-25 are rejected under 35 U.S.C. 103 as being unpatentable over Heidmann et al (WO2004087748A1), in view of Gagnepain (Thesis Dissertation, “Evaluation of new lentiviral vector pseudotypes for gene transfer into hematopoietic cells”, 2014), and Lavillette et al (J. of Virology, 2002), as applied to claims 16 and 18-22 above, and further in view of Fenard et al (WO2013001041A1).
Regarding claims 24-25, the limitations of the independent claim 16 are taught above.
Heidmann, Gagnepain, and Lavillette do not teach that the method is performed in the presence of LAH4 peptide or a functional derivative thereof as required by claim 24, nor that that the functional derivative is SEQ ID NO: 18 as required by claim 25.
However, Fenard teaches SEQ ID NO: 14 which is a sequence that is 100% identical to the instant SEQ ID NO: 18 (see STIC search results under Issued Patents for SEQ ID NO: 18). Fenard teaches that the LAH4 peptides taught, such as the LAH4 peptide of Fenard’s SEQ ID NO: 14, are used for improving the transduction efficiency of viruses into target cells (abstract). More specifically, Fenard teaches that the peptide is specifically beneficial in promoting the infection of a eukaryotic cell by a virus or viral vector (pg. 3, para 5).
One of ordinary skill in the art would find it obvious at the effective filling date of the instant invention to combine the lentiviral expression including syncytin for therapeutic use taught by Heidmann, Gagnepain, and Lavillette with the LAH4 peptide taught by Fenard to arrive at the instant invention. One of ordinary skill in the art would be motivated to make this combination because Fenard teaches that the LAH4 peptides taught, such as the LAH4 peptide of Fenard’s SEQ ID NO: 14, are used for improving the transduction efficiency of viruses into target cells (abstract). One of ordinary skill in the art would have a reasonable expectation of success when combining Heidmann, Gagnepain, and Lavillette with Fenard because Fenard teaches that the peptide is specifically beneficial in promoting the infection of a eukaryotic cell by a virus or viral vector (pg. 3, para 5).
Response to Arguments
Applicant’s arguments, see Remarks, filed 01/30/2026, with respect to the rejection(s) of claims 16 and 18-25 under 35 U.S.C. 103 have been fully considered and are persuasive. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of Heidmann, Gagnepain and Lavillette.
Declaration Under 37 C.F.R. § 1.132 of Anne Galy
The Declaration submitted under 37 C.F.R. § 1.132 by Anne Galy has been considered. The declaration focuses on the Frecha reference and concludes that one of ordinary skill in the art would not have been motivated to apply the teachings of Heidmann towards B cells. Although Frecha does concern the lentiviral transduction of B cells, it is focused on Measles virus-LVs which do not appear to be considered analogous or closely related to the endogenous retroviral syncytins of the instant invention. This is supported by Anne Galy. Therefore, the rejection employing Frecha to teach the application of the pseudotyped lentiviral particles of Heidmann in B cells, has been withdrawn. However, as described in the “Response to Arguments” section, a new ground(s) of rejection is made in view of Heidmann, Gagnepain and Lavillette.
Conclusion
No claims are allowed.
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CONSTANTINA E. STAVROU
Examiner
Art Unit 1632
/DAVID A MONTANARI/Examiner, Art Unit 1632