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 .
The preliminary amendment of 3/15/2023 has been received and entered into the application file.
Priority
This application claims benefit to US provisional application 63/269,440 (filed on 03/16/2022).
Election/Restrictions
Applicants elected without traverse Invention Group I, drawn to a method of making the HSV-vector based vector comprising a transgene, in reply filed on 05/01/2026 is acknowledged. Claims 1-21 read on the elected group.
Claims Status
Claims 1-39 are pending.
Claims 22-39 are withdrawn per restriction election (filed on 05/01/2026).
Claims 1-21 have been considered on the merits.
Drawings
The drawings filed on 03/15/2023 are objected to because they contain color images, but there is no granted petition for color drawings.
Color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
Claim Interpretation
Regarding claims 8-9,13-15, 17 and 19-20, the claim recites a product-by-process limitation. Product-by-process limitations are considered only insofar as the method of production imparts distinct structural or chemical characteristics or properties to the product. Therefore if the product, as claimed, is the same or obvious over a product of the prior art (i.e. is not structurally or chemically distinct), the claim is considered unpatentable over the prior art, even though the prior art product is made by a different process. See MPEP 2113.
In the instant case, claim 8 is directed to a composition. The composition is required to contain a non-replicating HSV-based vector with (i) a transgene and (ii) extracellular CD47 domain on the N-terminus of a glycoprotein. The claim states that the HSV is prepared by passaging at least twice the HSV vector with immune sera with anti-HSV antibodies. The result is a composition comprising HSV-based vector with components (i) and (ii), the passaging of the HSV-based vector in the immune sera does not change the structure of the HSV vector but neutralizes the surface proteins. Therefore, any composition comprising an HSV-based vector with a transgene and an extracellular CD47 domain attached to the N-terminus of glycoprotein that has been neutralized with immune sera would read on this limitation.
For claim 9, the resulting composition is also an HSV-based vector with components (i) and (ii), the passaging in immune sera does not change the structure of the HSV vector but neutralizes the surface proteins. Therefore, any composition comprising an HSV-based vector with a transgene and an extracellular CD47 domain attached to the N-terminus of glycoprotein that has been neutralized with immune sera would read on this limitation.
For claim 13, the resulting composition is also an HSV-based vector with components (i) and (ii), the passaging in a combination of rat and human immune sera does not change the structure of the HSV vector but neutralizes the surface proteins. Therefore, any composition comprising an HSV-based vector with a transgene and an extracellular CD47 domain attached to the N-terminus of glycoprotein that has been neutralized with immune sera would read on this limitation.
For claim 14, the resulting composition is also an HSV-based vector with components (i) and (ii), the passaging in rat immune sera and the combination of rat and human immune sera does not change the structure of the HSV vector but neutralizes the surface proteins. Therefore, any composition comprising an HSV-based vector with a transgene and an extracellular CD47 domain attached to the N-terminus of glycoprotein that has been neutralized with immune sera would read on this limitation.
For claim 15, the composition requires an HSV-based vector comprising a transgene and that the HSV vector is prepared by passaging in immune sera with anti-HSV antibodies. The result is a composition comprising an HSV-based vector with a transgene with neutralized surface proteins. Therefore, any composition comprising an HSV-based vector with a transgene that has been neutralized by immune sera would satisfy this limitation.
For claim 17, the resulting composition is also an HSV-based vector with a transgene, the passaging in immune sera does not change the structure of the HSV vector but neutralizes the surface proteins. Therefore, any composition comprising an HSV-based vector with a transgene that has been neutralized with immune sera would read on this limitation.
For claim 19, the resulting composition is also an HSV-based vector with a transgene, the passaging in a combination of rat and human immune sera does not change the structure of the HSV vector but neutralizes the surface proteins. Therefore, any composition comprising an HSV-based vector with a transgene that has been neutralized with immune sera would read on this limitation.
For claim 20, the resulting composition is also an HSV-based vector with a transgene, the passaging in rat immune sera and the combination of rat and human immune sera does not change the structure of the HSV vector but neutralizes the surface proteins. Therefore, any composition comprising an HSV-based vector with a transgene that has been neutralized with immune sera would read on this limitation.
Claim Objections
Claim 12 is objected to because of the following informalities:
In claim 12, the full term 'glycoprotein E' should precede the first use of acronym "gE" in line 2.
Appropriate correction is required.
Claim Rejections - 35 USC § 102
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 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 1-5 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Fu et al (Oncotarget, 2018; as cited in the IDS filed on 3/15/2023; referred to as Fu et al (2018)).
Fu et al (2018) teaches genetically engrafting CD47 to the membrane envelope of an oncolytic herpes simplex virus (HSV) that leads to the virus more efficiently delivering to local tumors and an increase in virus persistence in local tumors (See, Abstract).
Regarding claims 1-5, Fu et al (2018) teaches that HSV encodes several glycoproteins on their viral envelop, such as glycoprotein C (gC), gB, gD, gH, and gL (See, p34544 col 1 paragraph 2). This reads on, …(ii) the HSV vector has a membrane envelope comprising glycoproteins.
Fu et al (2018) teaches the engraftment of the extracellular domain of murine CD47 (mCD47) to the gC of HSV, at the N-terminus to create a chimeric glycoprotein C (cgC) with a CMV promoter, an HA tag and EGFP-luciferase gene (See, p34544 col 1 paragraph 2). This reads on, wherein (i) the HSV vector comprises a transgene, as eGFP is a transgene, and on wherein at least one glycoprotein comprises an extracellular domain into the N-terminus of the glycoprotein. This also reads on, wherein the glycoprotein is glycoprotein C of claims 4 and 5.
This was inserted into FusOn-H3 backbone, which is derived from HSV-2 and FusOn-CD47-Luc is new the HSV-based vector (See, p34544 col 1 and Figure 1). This reads on, a nonreplicating HSV based gene delivery vector of claim 1. This also reads on, wherein the HSV vector is HSV-2 vector of claim 2.
Fu et al (2018) verified that the presence of mCD47 ECD on the viral particles from FusOn-CD47-Luc allow for the resistance of macrophages during infection (See, p;34544 col 2 paragraph 2). This reads on, wherein the HSV-based vector is an HSV amplicon packaged into a viral particle of claim 3.
Therefore, claims 1-5 are anticipated by Fu et al (2018).
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.
Claim 6 is rejected under 35 U.S.C. 103 as being unpatentable over Fu et al (Oncotarget, 2018; as cited in the IDS filed on 3/15/2023 as applied to claims 1-5 above; referred to as Fu et al (2018)), and further in view of Fu et al (Molecular therapy oncolytics, 2020; referred to as Fu et al (2020)).
The teachings of Fu et al (2018) have been set forth above.
Regarding claim 6, following the discussion above of claim 1, Fu et al (2018) does not teach where in the HSV-based vector the transgene is a therapeutic gene. eGFP cannot be considered a therapeutic gene.
Fu et al (2020) teaches a method of redirecting innate immune cells to attack tumors by engaging the immune cells with herpes simplex virus (HSV) derived oncolytic viruses with secreted chimeric molecules (See, Abstract).
Fu et al (2020) teaches chimeric molecules, HER2 affibody-PL and EGF-PL, that are then inserted into genome of oncolytic HSVs into the intergenic region of UL46 and UL47 of Synco-2D, an HSV-1 based virus, and on FusOn-H2, an HSV2 based virus (See, p35-36 and Figure 1). The HSV1 and HSV2 viruses with the affibody-PL inserts are named Synco-4 and FusOn-PL, respectively (See, p36 col 1).
Fu et al (2020) teaches that he therapeutic effect of the FusOn-PL is an enhancement of the antitumor effect of the virotherapy and there was an increase in NKs in tumor tissues but not proliferation, indicating it affects NK recruitment not NK proliferation (See, p38 col 1-2).
Fu et al (2020) teaches that potential modification would be to incorporate immune stimulatory genes into the viral genome to enhance antitumor immunity or combining virotherapy with immune checkpoint inhibitors (See, p40 col 1).
It would have been prima facie obvious to a person having ordinary skill in the art to have modified the HSV-based vector of Fu et al (2018) such that the transgene is a therapeutic gene, such as HER2-affibody PL, as taught in Fu et al (2020). This conclusion of obviousness is based on teaching suggestion motivation rationale. One would have been motivated to make this modification enhance the antitumor effect of the HSV virotherapy. One would have had a reasonable expectation of success evidenced by Fu et al (2020).
Therefore, claim 6 a are rendered obvious over Fu et al (2018) in view of Fu et al (2020).
Claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over Fu et al (Oncotarget, 2018; as cited in the IDS filed on 3/15/2023) as applied to claims 1-5 above, and further in view of Sosale et al (Molecular therapy, 2016).
The teachings of Fu et al (2018) have been set forth above.
Regarding claim 7, following the discussion above of claims 1, Fu et al (2018) does not teach an HSV-based vector wherein the ECD CD47 is ECD human CD47.
Sosale et la teaches that lentivirus with human-CD47 (hCD47) prolongs circulation of the injected gene delivery system and show enhanced transduction of efficient CRISPR/Cas9 delivery shown by efficient gene deletion (See, Abstract).
Sosale et al teaches a lentiviral vector with full length human CD47-GFP construct, which includes the ECD as seen in green in Figure 1 (See, p 2 col 1 paragraph 2 and Figure 1). Sosale et al further teaches that injection of hCD47 lentivirus, resulted in increased circulation, decreased uptake by macrophages and increased transduction or gene delivery (See, p9 col 1 paragraph 1).
Given that both Fu et al (2018) and Sosale et al teach gene delivery vectors, it would have been prima facie obvious to a person having ordinary skill in the art to substitute the ECD mCD47 in the HSV-based vector of Fu et al (2018) with the hCD47 of Sosale et al for a similar purpose. The use of ECD hCD47 would have predictable results of success evidenced by Sosale et al. This rationale aligns with the principle of KSR for simple substitution of one known element for another to obtain predictable results (See, MPEP 2143).
Therefore, claim 7 is rendered obvious over Fu et al (2018) in view of Sosale et al.
Claims 8-10,13-17, and 19-20 are rejected under 35 U.S.C. 103 as being unpatentable over Fu et al (Oncotarget, 2018; as cited in the IDS filed on 3/15/2023) as applied to claims 1-5 above, and further in view of Wakimoto et al (Molecular therapy: the journal of the American society of gene therapy, 2002) and Rojas et al (Journal of Virology, 1992); evidenced by Cairns et al (Journal of virology, 2015)
The teachings of Fu et al (2018) are set forth above.
Regarding claims 8,15,16, following the discussion above, claims 8 is product-by-process claim, therefore, the HSV-based vector, FusOn-CD47-Luc of Fu et al (2018) satisfies the vector component of the claim 8 and 15, as it has a transgene and a CD47 at the gC N-terminus. For claim 16, FusOn-CD47-Luc is on HSV-2.
Fu et al (2018) does not teach the passaging of the HSV vector at least twice in immune sera with elevate levels of anti-HSV antibodies.
Rojas et al teaches selection of foot-and-mouth disease virus (FMDV) antibody resistant antibodies after serial passaging in the presence of neutralizing antiviral polyclonal sera (APS) resulted in increased resistance to neutralization from APS (See, abstract).
Rojas et al teaches that characteristics from the immune sera passaging persists after 14 passages and Rojas et al went as far as 29 passages (See, Abstract).
Wakimoto et al teaches complement activities against an oncolytic HSV in in vitro studies using rat, mouse, and human serum that leads to the neutralization of herpes simplex oncolytic viruses (OV) (See, Abstract).
Wakimoto et al teaches undiluted human serum inactivates greater than 88% of oncolytic virus; sera from mice exposed to HSV, had antiviral potency similar to human sera; rat sera was most potent. Resulting in mice, rat, and human era inactivates or neutralizes an oncolytic virus at different potencies (See, p276 col1 paragraph 1). Wakimoto et al teaches the findings are relevant to the improve efficacy and application in human clinical trials (See, p275 col 2 paragraph 2).
Wakimoto et al teaches that complementation from mice, rats and humans, were achieved through different pathways. In humans, the complement of HSV OV occurred through binding immunoglobulins. In mice, that complement of HSV OV occurred through the lectin pathway. In rats, both pathways (immunoglobulins and lectin pathway) were complicit (See, p279 col 1 paragraph 1).
It would have been prima facie obvious to a person having ordinary skill in the art to have modified the method of Fu et al (2018) to comprise passaging the HSV vectors in immune sera at least twice as taught by Rojas et al. This conclusion of obviousness is based on teaching suggestion motivation rationale. One would have been motivated by the teachings of Rojas et al and Wakimoto et al, as both teach the benefits of neutralizing viruses to increase their efficacy and resistance to neutralization upon administration. One would have had a reasonable expectation of success evidenced by Rojas et al and Wakimoto et al.
Regarding claims 9 and 17, following the discussion above, claim 9 is a product by process claim. Fu et al, Rojas et al, and Wakimoto et al are silent on the immune sera’s ability to neutralize epitopes on glycoprotein B (gB) and glycoprotein D (gD) of the HSV-based vector. Yet, these properties are inherent due to the immune sera having elevated levels of anti-HSV. Cairns et al teaches that people infected with HSV produce neutralizing antibodies against glycoprotein D or both glycoprotein B and D (See, p9213 paragraph 2). Therefore, immune sera with elevated levels of anti-HSV will have neutralizing antibodies against gD and gB and passaging the vectors in the sera would neutralize the glycoproteins.
Regarding claim 10, following the discussion above, Fu et al (2018) teaches the extracellular domain (ECD) of mCD47 that was inserted into the vector comprises amino acid 19 to 161 (See, p34544 col 1 paragraph 1). This reads on, wherein the ECD CD47 domain comprises amino acids 19-141 of claim 10, as the ECD mCD47 of Fu et al includes the claimed range of amino acids.
Regarding claim 13 and 19, following the discussion above, Fu et al teach the immune sera being a mixture of rat and human era with elevated levels of anti-HSV antibodies.
It would have been obvious to a person having ordinary skill in the art to have further modify the method Fu et al, such that the immune sera that the HSV vector is being passaged in comprises a combination of rat and human sera with elevated levels of anti-HSV antibodies. This conclusion of obviousness is based on teaching suggestion motivation rationale. One would have been motivated by Wakimoto et al that teaches that rat and human sera activate complementation or neutralization by different pathways and have different potencies depending on the dilution (See, Figure 1 and p279 col 1 paragraph 2). Therefore, combining the rat and human sera for the passaging would result in increased neutralization and by different pathways, that would only further improve the efficacy of the HSV-based vector. One would have had a reasonable expectation of success evidenced by Wakimoto et al.
Regarding claim 14 and 20, following the discussion above, Fu et al does not teach passaging at least two in rat sear followed by passaging at least twice in mixture of rat sera, and at least one human serum.
It would have been obvious to a person having ordinary skill in the art to have further modify the method Fu et al, such that the immune sera that the HSV vector is passaged at least two in rat sera with elevated levels of anti-HSV followed by passaging at least twice in mixture of rat sera, and at least one human serum with elevate level of anti-HSV antibodies. This conclusion of obviousness is based on teaching suggestion motivation rationale. One would have been motivated by Wakimoto et al that teaches that rat and human sera activate complementation or neutralization by different pathways and have different potencies depending on the dilution (See, Figure 1 and p279 col 1 paragraph 2). Therefore, combining the rat and human sera for the passaging would result in increased neutralization and by different pathways, that would only further improve the efficacy of the HSV-based vector. Also motivated by Rojas et al that teaches that multiple passages in immune sera increases the neutralization resistance upon administration. One would have had a reasonable expectation of success evidenced by Wakimoto et al and Rojas et al.
Therefore, claims 8-101,13-17,and 19-20 are rendered obvious over Fu et al (2018) in view of Rojas et al and Wakimoto et al; evidenced by Cairns et al.
Claims 12 and 18 are rejected under 35 U.S.C. 103 as being unpatentable over Fu et al (Oncotarget, 2018; as cited in the IDS filed on 3/15/2023), Wakimoto et al (Molecular therapy: the journal of the American society of gene therapy, 2002), and Rojas et al (Journal of Virology, 1992) as applied to claims 8-10,13-17, and 19-20 above, and further in view of Wang et al (Virology, 2010).
The teachings of Fu et al (2018), Wakimoto et al, and Rojas et al have been set forth above.
Regarding claims 12 and 18, following the discussion of claims 8 and 15 above, Fu et al (2018), Wakimoto et al nor Rojas et al teach wherein the HSV-based vector is free or substantially free of glycoprotein E (gE).
Wang et al teaches the role of HSV-gE in mediating virus spread, which includes the virus ability to spread between adjacent epithelial cells or between epithelial cells and neurons (See, p269 col 1 paragraph 2). Wang et al teaches the use of HSV-2 vector with glycoprotein E (gE) deleted from amino acids 124-495 and replaced with GFP2 (Se, p274 col 1 paragraph 3). Wang et al further teaches that the in vitro and in vivo approaches of HSV-gE mutant has defective ability to spread from epithelial cells to neurons and makes it a candidate for attenuated live virus vaccine (See, p273 col 2 paragraph 3).
It would have been prima facie obvious to a person having ordinary skill in the art to have modified the HSV-based vector of Fu et al (2018) such that the HSV-based vector be free or substantially free of gE, as taught in Wang et al. This conclusion of obviousness is based on teaching suggestion motivation rationale. One would have been motivated to make this modification to enhance the HSV-based vector and prevent its spread to neuronal cells. One would have had a reasonable expectation of success evidenced by the teachings of Wang et al.
Therefore, claims 12 and 18 are rendered obvious over Fu et al (2018), Wakimoto et al, and Rojas et al in further view of Wang et al.
Claim 11 is rejected under 35 U.S.C. 103 as being unpatentable over Fu et al (Oncotarget, 2018; as cited in the IDS filed on 3/15/2023), Wakimoto et al (Molecular therapy: the journal of the American society of gene therapy, 2002), and Rojas et al (Journal of Virology, 1992) as applied to claims 8-10,13-17, and 19-20 above, and further in view of Sosale et al (Molecular therapy, 2016).
The teachings of Fu et al (2018), Wakimoto et al, and Rojas et al have been set forth above.
Regarding claim 11, following the discussion above of claim 8, Fu et al (2018), Wakimoto et al, nor Rojas et al teach an HSV-based vector wherein the ECD CD47 is ECD human CD47.
Sosale et la teaches that lentivirus with human-CD47 (hCD47) prolongs circulation of the injected gene delivery system and show enhanced transduction of efficient CRISPR/Cas9 delivery shown by efficient gene deletion (See, Abstract).
Sosale et al teaches a lentiviral vector with full length human CD47-GFP construct, which includes the ECD as seen in green in Figure 1 (See, p 2 col 1 paragraph 2 and Figure 1). Sosale et al further teaches that injection of hCD47 lentivirus, resulted in increased circulation, decreased uptake by macrophages and increased transduction or gene delivery (See, p9 col 1 paragraph 1).
Given that both Fu et al (2018) and Sosale et al teach gene delivery vectors, it would have been prima facie obvious to a person having ordinary skill in the art to substitute the ECD mCD47 in the HSV-based vector of Fu et al (2018) with the hCD47 of Sosale et al for a similar purpose. The use of ECD hCD47 would have predictable results of success evidenced by Sosale et al. This rationale aligns with the principle of KSR for simple substitution of one known element for another to obtain predictable results (See, MPEP 2143).
Therefore, claim 11 is rendered obvious over Fu et al (2018), Wakimoto et al, and Rojas et al, in further view of Sosale et al.
Claim 21 is rejected under 35 U.S.C. 103 as being unpatentable over Fu et al (Oncotarget, 2018; as cited in the IDS filed on 3/15/2023), Wakimoto et al (Molecular therapy: the journal of the American society of gene therapy, 2002), and Rojas et al (Journal of Virology, 1992) as applied to claims 8-10,13-17, and 19-20 above, and further in view of Fu et al (Molecular therapy oncolytics, 2020; referred to as Fu et al (2020))
The teachings of Fu et al (2018), Wakimoto et al, Rojas et al, and Fu et al (2020) have been set forth above.
Regarding claim 21, following the discussion above of claim 15, Fu et al (2018), Wakimoto et al, nor Rojas et al teach where in the HSV-based vector the transgene is a therapeutic gene, as eGFP cannot be considered a therapeutic gene.
Fu et al (2020) teaches chimeric molecules, HER2 affibody-PL and EGF-PL, that are then inserted into genome of oncolytic HSVs into the intergenic region of UL46 and UL47 of Synco-2D, an HSV-1 based virus, and on FusOn-H2, an HSV2 based virus (See, p35-36 and Figure 1). The HSV1 and HSV2 viruses with the affibody-PL inserts are named Synco-4 and FusOn-PL, respectively (See, p36 col 1).
It would have been prima facie obvious to a person having ordinary skill in the art to have modified the HSV-based vector of Fu et al (2018) such that the transgene is a therapeutic gene, such as HER2-affibody PL, as taught in Fu et al (2020). This conclusion of obviousness is based on teaching suggestion motivation rationale. One would have been motivated to make this modification enhance the antitumor effect of the HSV virotherapy. One would have had a reasonable expectation of success evidenced by Fu et al (2020).
Therefore, claim 21 is rendered obvious over Fu et al (2018), Wakimoto et al, and Rojas et al, in further view of Fu et al (2020).
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.
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.
Claims 1-21 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 4, 6, and 7 of copending Application No. 18/264,737 (reference app) in view of Fu et al (Oncotarget, 2018; as cited in the IDS filed on 3/15/2023), Fu et al (Molecular therapy oncolytics, 2020; referred to as Fu et al (2020)), and Sosale et al (Molecular therapy, 2016).
The teachings for Fu et al (2018), Fu et al (2020), and Sosale et al have been set forth above.
Regarding claims 1-6,8-9,13-17, and 19-21, reference app claim 1 recites, a composition comprising an oncolytic HSV-1 or HSV-2, wherein the oncolytic HSV-l or HSV-2 is prepared by passaging at least twice an oncolytic HSV-l or HSV-2 with immune sera having elevated levels of anti-HSY antibodies, reference app claim 2 recites the composition of claim 1, wherein the oncolytic HSV-l or HSV-2 has a membrane envelope comprising glycoproteins, wherein at least one glycoprotein comprises an extracellular CD47 domain inserted into the N-terminus of a glycoprotein, reference app claim 3 recites, the composition of claim 2, wherein the glycoprotein is selected from glycoprotein C, glycoprotein B, glycoprotein D, glycoprotein H, and glycoprotein L, and lastly reference app claim 4 recites, the composition of claim 3, wherein the glycoprotein is glycoprotein C. In combination the resulting composition is an HSV-1 or HSV-2 vector comprising an ECD CD47 inserted into the N-terminus of glycoprotein C, therefore it would read on the instant claims but the reference app does not teach that the HSV-1 or HSV-2 composition, further comprises of a transgene.
Fu et al (2020) teaches chimeric molecules, HER2 affibody-PL and EGF-PL, that are then inserted into genome of oncolytic HSVs into the intergenic region of UL46 and UL47 of Synco-2D, an HSV-1 based virus, and on FusOn-H2, an HSV2 based virus (See, p35-36 and Figure 1). The HSV1 and HSV2 viruses with the affibody-PL inserts are named Synco-4 and FusOn-PL, respectively (See, p36 col 1).
It would have been prima facie obvious to a person having ordinary skill in the art to have modified the composition of HSV-1 or HSV-2 of the reference app, such that the HSV-1 and HSV-2 further comprise a therapeutic transgene such as HER2 affibody-PL, as taught in Fu et al (2020). This conclusion of obviousness is based on teaching suggestion motivation rationale. One would have been motivated to make this modification enhance the HSV composition to have added efficacy for targeting tumors. One would have had a reasonable expectation of success evidenced by the teachings of Fu et al (2020).
Therefore, claims 1-6,8-9,13-17, and 19-21 have been rendered obvious by reference app claims 1,2,3, and 4 in view of Fu et al.
Regarding claims 7 and 11, following the discussion above, the reference app does not teach the use of human CD47 ECD.
Sosale et al teaches a lentiviral vector with full length human CD47-GFP construct, which includes the ECD as seen in green in Figure 1 (See, p 2 col 1 paragraph 2 and Figure 1). Sosale et al further teaches that injection of hCD47 lentivirus, resulted in increased circulation, decreased uptake by macrophages and increased transduction or gene delivery (See, p9 col 1 paragraph 1).
Given that both the reference app and Sosale et al teach compositions of viral vectors that can be used for gene delivery, it would have been prima facie obvious to a person having ordinary skill in the art to substitute the non-specific ECD CD47 in the HSV-1 or HSV-2 of the reference app with the hCD47 of Sosale et al for a similar purpose. The use of ECD hCD47 would have predictable results of success evidenced by Sosale et al. This rationale aligns with the principle of KSR for simple substitution of one known element for another to obtain predictable results (See, MPEP 2143).
Therefore, claims 7 and 11 have been rendered obvious by reference app claims 1,2,3, and 4 in view of Sosale et al.
Regarding claim 10, following the discussion above, reference app claim 6 recites, wherein the extracellular CD47 domain comprises amino acids 19-141 of CD47.
The reference app does not teach the use of murine ECD CD47.
Fu et al teaches the extracellular domain (ECD) of mCD47 that was inserted into the vector comprises amino acid 19 to 161 (See, p34544 col 1 paragraph 1).
Given that both the reference app and Fu et al teach compositions of HSV-2, it would have been prima facie obvious to a person having ordinary skill in the art to substitute the non-specific ECD CD47 in the HSV-1 or HSV-2 of the reference app with the ECD mCD47 with amino acids 19-161, which includes amino acids 19-141, of Fu et al for a similar purpose. The use of ECD mCD47 would have predictable results of success evidenced by Fu et al. This rationale aligns with the principle of KSR for simple substitution of one known element for another to obtain predictable results (See, MPEP 2143).
Therefore, claim 10 has been rendered obvious by reference app claims 1-4 and 6 in view of Fu et al.
Regarding claims 12 and 18, following the discussion above, reference app claim 7 recites wherein the oncolytic HSV-l or HSV-2 having an extracellular CD47 domain is free or substantially free of gE. This reads on claims 12 and 18.
This is a provisional nonstatutory double patenting rejection.
Conclusion
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/CAROLINE M LARA/Examiner, Art Unit 1633
/ALLISON M FOX/Primary Examiner, Art Unit 1633
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