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 election of group III, claims 14-16 on September 9, 2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 17 and 18 were amended. New claims 26-28 were added. Claims 4, 7-13, and 25 were canceled. Claims 14-18 and 26-28 are pending and under examination in this Office action.
The requirement deemed proper and is therefore made FINAL.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on September 9, 2025 and May 25, 2022 have been considered by the examiner.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 14-18 and 26-28 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 14 is drawn to A recombinant modified Vaccinia virus Ankara (MVA) comprising:
(1) a nucleic acid encoding HER V-K-env/MEL; (ii) a nucleic acid encoding HERV-K gag; (iii) a nucleic acid encoding FOLR1 and PRAME, and (iv) a nucleic acid encoding 4-1BBL.
Claim 16 recites the recombinant MVA of claim 14 that is derived from MVA-BN as deposited at the European Collection of Cell Cultures (ECACC) under number V00083008.
The claims are rejected because of lack of written description support for the claimed recombinant MVA derived from MVA-BN as deposited at the European Collection of Cell Cultures (ECACC) under number V00083008. There is lack of written description support for the claimed derivatives.
The present specification defines the claimed derivatives as follows [0182] “Derivatives” of MVA-BN refer to viruses exhibiting essentially the same replication characteristics as MVA-BN, as described herein, but exhibiting differences in one or more parts of their genomes. MVA-BN, as well as derivatives thereof, are replication incompetent, meaning a failure to reproductively replicate in vivo and in vitro. More specifically in vitro, MVA-BN or derivatives thereof have been described as being capable of reproductive replication in chicken embryo fibroblasts (CEF), but not capable of reproductive replication in the human keratinocyte cell line HaCat (Boukamp et al. (1988) J. Cell Biol. 106: 761-771), the human bone osteosarcoma cell line 143B (ECACC Deposit No. 91112502), the human embryo kidney cell line 293 (ECACC Deposit No. 85120602), and the human cervix adenocarcinoma cell line HeLa (ATCC Deposit No. CCL-2). Additionally, MVA-BN or derivatives thereof have a virus amplification ratio at least two-fold less, more preferably three-fold less than MVA-575 in Hela cells and HaCaT cell lines. Tests and assay for these properties of MVA-BN and derivatives thereof are described in WO 02/42480 (U.S. Patent Application No. 2003/0206926) and WO 03/048184 (U.S. Patent App. No. 2006/0159699).
Specification [0181] Example of MVA virus strains that are useful in the practice of the present invention and that have been deposited in compliance with the requirements of the Budapest Treaty are strains MVA 572, deposited at the European Collection of Animal Cell Cultures (ECACC), Vaccine Research and Production Laboratory, Public Health Laboratory Service, Centre for Applied Microbiology and Research, Porton Down, Salisbury, Wiltshire SP4 OJG, United Kingdom, with the deposition number ECACC 94012707 on Jan. 27, 1994, and MVA 575, deposited under ECACC 00120707 on Dec. 7, 2000, MVA-BN, deposited on Aug. 30, 2000 at the European Collection of Cell Cultures (ECACC) under number V00083008, and its derivatives, are additional exemplary strains.
It is noted that the MVA-BN as deposited at the European Collection of Cell Cultures (ECACC) under number V00083008 is a particular MVA strain previously disclosed in Lauterbach et al. (WO 2014/037124 in IDS on May 25, 2022) and the other species of the claimed derivatives such as ECACC 94012707 on Jan. 27, 1994, and MVA 575, deposited under ECACC 00120707 on Dec. 7, 2000, MVA-BN, deposited on Aug. 30, 2000 at the European Collection of Cell Cultures (ECACC) under number V00083008, and its derivatives, are additional exemplary strains, that do not appear to be derived from V00083008.
It does not appear, based on the teachings in the prior art disclosing the European Collection of Cell Cultures (ECACC) under number V00083008, including the teaching of Maisinger-Henschel et al. (Journal of Virology, 2010, p. 9907-9919), that this particular MVA-BN strain includes any derivatives. The recitation of derivatives, implies a large genus of virus particles that may be related to the (ECACC) number V00083008. However, Applicants specification fails to provide an adequate written description support for the claimed genus. The claims are rejected because the genus of the claimed derivatives is not sufficiently described in Applicant’s specification.
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 14-18 and 26-28 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 14 is drawn to A recombinant modified Vaccinia virus Ankara (MVA) comprising:
(1) a nucleic acid encoding HER V-K-env/MEL; (ii) a nucleic acid encoding HERV-K gag; (iii) a nucleic acid encoding FOLR1 and PRAME, and (iv) a nucleic acid encoding 4-1BBL.
Specification paragraph [0275] states: In one embodiment, the nucleic acid in (i) encodes a HERV-K-env/MEL comprising a HERV-K-env surface (SU) and transmembrane (TM) unit, wherein the TM unit is mutated, preferably wherein the TM unit is mutated such that an immunosuppressive domain is inactivated. Preferably, HERVK-MEL is inserted within the mutated TM unit. More preferably, HERVK-MEL replaces a portion of the immunosuppressive domain of the TM unit.
The claims are rejected because there metes and bounds of the recitation of “MEL” in HERV-K-env/MEL cannot be determined. The present claims do not recite any mutations in HERV-K-env and the recitation of “MEL” is not an art recognized acronym but Applicant’s own designation. The recitation of “MEL” is thus deemed indefinite. The present rejection can be overcome by amending the claims to recite the structural parameters of “MEL”. Correction and/or clarification is required.
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.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 14-18 and 26 are rejected under 35 U.S.C. 103 as being unpatentable over Lauterbach et al. (WO 2014/037124 in IDS on May 25, 2022) in view of Kraus et al. (PLOS, 2013, Vol. 8, p. 3-8) and further in view of Kraus et al. (Virology Journal, 2014, p. 1-7) and Kim et al. (PloSOne, 2018, p. 1-10).
Lauterbach et al. teaches pharmaceutical preparations comprising recombinant modified vaccinia virus Ankara, MVA BN, deposited at the European Collection of Cell Cultures (ECACC) under number V00083008 comprising a nucleic acid encoding PRAME, 4-1BBL and the nucleic acid encoding CD40L (see claims 1-44, page 51, first paragraph, paragraph [0126], and Examples 1-10).
Regarding present claim 15. Lauterbach et al. teaches MVA comprising the nucleic acid encoding CD40L (see Example 9, paragraphs [0178-0180]).
Regarding present claim 16. Lauterbach et al. teaches MVA-BN as deposited at the European Collection of Cell Cultures (ECACC) under number V00083008 (see page 51, first paragraph).
Regarding present claim 18. Lauterbach et al. teaches the recombinant MVA composition adapted for intravenous administration (see Example 5 on pages 67-70).
Regarding present claims 14 and 26. Lauterbach et al. teach PRAME (see claim 44). It is noted that the generation of the fusion protein comprising the FOLR1 and FRAME would have been prima facie obvious based on the knowledge of FOLR1 and FRAME in the prior art and considering that Lauterbach et al. expressly teaches generation of fusion proteins (see Examples 1-10).
Lauterbach et al. does not teach FORL1, HERV-K-env/MEL or HERV-K gag.
The present specification defines HERV-K-env/MEL, PRAME and FOLR1 as follows:
Specification paragraph [0275] In one embodiment, the nucleic acid in (i) encodes a HERV-K-env/MEL comprising a HERV-K-env surface (SU) and transmembrane (TM) unit, wherein the TM unit is mutated, preferably wherein the TM unit is mutated such that an immunosuppressive domain is inactivated. Preferably, HERVK-MEL is inserted within the mutated TM unit. More preferably, HERVK-MEL replaces a portion of the immunosuppressive domain of the TM unit.
Specification paragraph [0040] In other preferred embodiments, the first nucleic acid encodes a TAA selected from the group consisting of: carcinoembryonic antigen (CEA), mucin 1 cell surface associated (MUC-1), prostatic acid phosphatase (PAP), prostate specific antigen (PSA), human epidermal growth factor receptor 2 (HER-2), survivin, tyrosine related protein 1 (TRP1), tyrosine related protein 1 (TRP2), Brachyury, Preferentially Expressed Antigen in Melanoma (PRAME), Folate receptor 1 (FOLR1), and combinations thereof.
Kraus et al. (2014) teach a recombinant MVA comprising HERV-K gag protein (see Results, Methods and Figure 1).
Kraus et al. (2013) teach HERV-K-env/MEL comprising a HERV-K-env surface (SU) and transmembrane (TM) unit, wherein the TM unit is mutated and methods of vaccinating mice to treat lung tumor (see Materials and Methods and Results). The present claims however do not recite any mutations in HERV-K-env and the recitation of “MEL” is not an art recognized acronym but Applicant’s own designation.
Kim et al. teach folate receptor, FOLR1 targeted chimeric antigen receptor T cells for the treatment of gastric cancer (see
It would have been prima facie obvious to provide Lauterbach et al. MVA further comprising Kraus’ (2014) recombinant MVA comprising HERV-K gag protein because Kraus (2014) teaches effective treatment of a lung tumor in mice treated with recombinant MVA comprising HERV-K gag protein (see Results, Methods and Figure 1).
It would have been prima facie obvious to provide Lauterbach et al. MVA further comprising Kraus’ (2013) recombinant MVA HERV-K-env/MEL because Kraus (2013) teaches that a single vaccination of tumor-bearing mice with MVA-HERV-K env drastically reduced the number of pulmonary RLZ-HERV-K env tumor nodules compared to vaccination with wild-type MVA and teaches that the vaccination of mice with MVA-HKenv precluded the formation of RLZ-HERV-K env tumor nodules, whereas wild-type MVA-vaccinated animals succumbed to metastasis (see Abstract, Results and Figure 4).
It would have been prima facie obvious to provide Lauterbach et al. MVA further comprising Kim et al. folate receptor, FOLR1, because Kim teaches that FOLR1 is overexpressed in gastric cancer patients and teaches that inducing an immune response against FOLR1 was effective to eliminate FOLR1 positive cancer cells (see Results).
Thus, the present invention would have been prima facie obvious at the time when the invention was made.
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 §§ 706.02(l)(1) - 706.02(l)(3) 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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
Claims 14, 16-18, and 26 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 of U.S. Patent No. 12,390,515. Although the claims at issue are not identical, they are not patentably distinct from each other because: The present claims are drawn to A recombinant modified Vaccinia virus Ankara (MVA) comprising:
(1) a nucleic acid encoding HER V-K-env/MEL; (ii) a nucleic acid encoding HERV-K gag; (iii) a nucleic acid encoding FOLR1 and PRAME, and (iv) a nucleic acid encoding 4-1BBL.
The claims of the U.S. Patent No. 12,390,515 are drawn to A method of inducing an enhanced inflammatory response in a cancerous tumor of a subject, the method comprising intratumorally administering to the subject a recombinant modified Vaccinia Ankara (MVA) comprising a first nucleic acid encoding a first heterologous tumor-associated antigen (TAA) that is an endogenous retroviral (ERV) protein expressed in a tumor cell and a second nucleic acid encoding a 4-1BBL antigen, wherein the intratumoral administration of the recombinant MVA generates an enhanced inflammatory response in the tumor as compared to an inflammatory response generated by a non-intratumoral injection of a recombinant MVA virus comprising a first and second nucleic acid encoding said TAA and a 4-1BBL antigen.
The claims of the U.S. Patent No. 12,390,515 are also drawn A method of inducing an enhanced inflammatory response in a cancerous tumor of a subject, the method comprising administering to the subject a recombinant modified Vaccinia Ankara (MVA) comprising a first nucleic acid encoding a first heterologous tumor-associated antigen (TAA) that is an endogenous retroviral (ERV) protein expressed in a tumor cell, a second nucleic acid encoding a 4-1BBL antigen, and a third nucleic acid encoding a CD40L antigen, wherein the administration of the recombinant MVA generates an enhanced inflammatory response in the tumor as compared to an inflammatory response generated by administration of a recombinant MVA, 4-1BBL antigen, and CD40L antigen by themselves.
The present claims are obvious over the claims of the U.S. Patent No. 12,390,515 because the present claims are drawn to a product and the claims and the claims of the U.S. Patent No. 12,390,515 are drawn to the method of using the product presently claimed. The difference between the present claims and the claims of the U.S. Patent No. 12,390,515 is that the claimed product requires all: a nucleic acid encoding HER V-K-env/MEL; (ii) a nucleic acid encoding HERV-K gag; (iii) a nucleic acid encoding FOLR1 and PRAME, and (iv) a nucleic acid encoding 4-1BBL, while the product used in the method of U.S. Patent No. 12,390,515 does nor require all HER V-K-env/MEL; (ii) a nucleic acid encoding HERV-K gag; (iii) a nucleic acid encoding FOLR1 and PRAME together.
The present product is otherwise obvious over the method of using the product disclosed in U.S. Patent No. 12,390,515. Thus, the present claims are obvious over the claims of U.S. Patent No. 12,390,515.
Conclusion
SEQ ID NO: 9, 11 and 12 are free of prior art.
Pertinent prior art
Holst et al. (US Patent 11,351,247) teaches a sequence having 91.5 % identity with present SEQ ID NO: 11 (see SEQ ID NO: 48). Holst et al. do not teach a sequence having 100% identity with present SEQ ID NO: 11.
Query Match 91.5%; Score 2519; Length 1387;
Best Local Similarity 95.0%;
Matches 472; Conservative 5; Mismatches 4; Indels 16; Gaps 2;
Qy 1 MNPSEMQRKAPPRRRRHRNRAPLTHKMNKMVTSEEQMKLPSTKKAEPPTWAQLKKLTQLA 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 689 MNPSEMQRKAPPRRRRHRNRAPLTHKMNKMVTSEEQMKLPSTKKAEPPTWAQLKKLTQLA 748
Qy 61 TKYLENTKVTQTPESMLLAALMIVSMVVSLPMPAGAAAANYTYWAYVPFPPMIRAVTWMD
|||||||||||||||||||||||||||||||||||||||||||||||||||:||||||||
Db 749 TKYLENTKVTQTPESMLLAALMIVSMVVSLPMPAGAAAANYTYWAYVPFPPLIRAVTWMD 808
Qy 121 NPIEVYVNDSVWVPGPIDDRCPAKPEEEGMMINISIGYRYPPICLGRAPGCLMPAVQNWL
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 809 NPIEVYVNDSVWVPGPIDDRCPAKPEEEGMMINISIGYRYPPICLGRAPGCLMPAVQNWL 868
Qy 181 VEVPTVSPISRFTYHMVSGMSLRPRVNYLQDFSYQRSLKFRPKGKPCPKEIPKESKNTEV
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 869 VEVPTVSPISRFTYHMVSGMSLRPRVNYLQDFSYQRSLKFRPKGKPCPKEIPKESKNTEV 928
Qy 241 LVWEECVANSAVILQNNEFGTIIDWAPRGQFYHNCSGQTQSCPSAQVSPAVDSDLTESLD
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 929 LVWEECVANSAVILQNNEFGTIIDWAPRGQFYHNCSGQTQSCPSAQVSPAVDSDLTESLD 988
Qy 301 KHKHKKLQSFYPWEWGEKGISTPRPKIISPVSGPEHPELWRLTVASHHIRIWSGNQTLET
|||||||||||||||||||||||||||:||||||||||||||||||||||||||||||||
Db 989 KHKHKKLQSFYPWEWGEKGISTPRPKIVSPVSGPEHPELWRLTVASHHIRIWSGNQTLET 1048
Qy 361 RDRKPFYTVDLNSSLTVPLQSCVKPPYMLVVGNIVIKPDSQTITCENCRLLTCIDSTFNW
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1049 RDRKPFYTVDLNSSLTVPLQSCVKPPYMLVVGNIVIKPDSQTITCENCRLLTCIDSTFNW 1108
Qy 421 QHRILLVRAREGVWIPVSMDRPWEASPSVHILTEVLKGVLN--------MLAVI------
||||||||||||||||||||||||||||||||||||||||| ::|||
Db 1109 QHRILLVRAREGVWIPVSMDRPWEASPSVHILTEVLKGVLNRSKRFIFTLIAVIMGLIAV 1168
Qy 467 --SCAVAGVALHGSAGS 481
: |||||||| | |
Db 1169 TATAAVAGVALHSSVQS 1185
Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AGNIESZKA BOESEN whose telephone number is (571)272-8035. The examiner can normally be reached on 8:30 - 5:00 PM.
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/AGNIESZKA BOESEN/Primary Examiner, Art Unit 1648