Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, 17919052, (PGP 20230263909A1), filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 1,3,12-17,21,23,24,26,28,43,45,48,52,54,57,61 are pending.
Priority
The filing receipt, mailed 9/13/2023, states that the Domestic Priority, as claimed by applicant, is this application is a 371 of PCT/US2021/027167, 04/13/2021, which claims benefit of 63/010,028, filed 04/14/2020.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on12/23/2025, is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Response to Arguments
The rejection of Claims 14, 15-17, 21 and 52 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, is withdrawn in view of applicant’s amendments to the claims and arguments, filed 12/23/2025.
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.
The factual inquiries 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.
Claim(s) 1,3,12-17,21,23,24,26,28,43,45,48,52,54,57,61 is/are rejected under 35 U.S.C. 103 as being unpatentable over Hoffman, US 2017/0043036 A1, published Feb. 16, 2017, (of record, Serial No: 15306163) and Riedel, US 20220370470 A1, (foreign priority to GB 1909506.6, filed 2019-07-02).
Hoffman teaches a method of treating a mammal in need thereof (para [0008), viral vector-based gene therapy methods for treating and/or ameliorating one or more of symptoms of autoimmune diseases, including, for example, MS.) comprising administering to the mammal a therapeutically-effective amount of: (a) a first composition comprising a recombinant adeno-associated viral (rAAV) vector comprising a polynucleotide that comprises a first nucleic acid segment that encodes a mammalian myelin basic protein (MBP), a proteolipid protein (PLP), or a myelin oligodendrocyte glycoprotein (MOG), (para [0009]), operably linked to a promoter (para [0016], [0067])that is capable of expressing the first nucleic acid segment in one or more cells of a mammalian liver (para [0132]-[0139]), hepatocyte-restricted expression of an AAV-delivered neuroantigen establishes persistent immunological tolerance mediated by antigen-specific Tregs capable of preventing and reversing EAE in mice.; [0134], Hepatic gene transfer with AAV vectors containing liver specific promoters can produce stable transgene expression and induce a robust antigen-specific immune tolerance to a variety of therapeutic proteins.; [0136], an AAV8-MOG vector was generated.; [0139], This example shows that liver directed gene transfer using an AAV vector expressing a neuro-antigen is capable of suppressing inflammation in the CNS and preventing EAE.); and (b) a second composition comprising an agent selected from an mTOR inhibitor, a sphingosine analog, a glucocorticoid, and a monoclonal antibody (para [0192], Regardless of AAV8 administration, treatment with rapamycin alone is expected to transiently produce a rapid reduction in the clinical presentation of EAE because It selectively Inhibits Teff proliferation. However, when used in conjunction with AAV8 liver gene transfer, rapamycin treatment has a synergistic effect that results in an increase in vector induced Ag-specific FoxP3+ Tregs (since they are less sensitive to mTOR signaling inhibition) with a corresponding decrease in effector T cells. The shift to tolerance is further potentiated by the fact Tregs have been shown to mediate selective inhibition of antigen-specific Th1 cells in the CNS of EAE.).
Hoffman teaches throughout the publication and at: [0137]-[0138], SEQ ID NO:1, as in claim 3; [0016], polynucleotides further comprising an enhancer, a post-transcriptional regulatory sequence, a polyadenylation signal, or any combination thereof, operably linked to the first nucleic acid segment, as claim 12; [0066], inverted terminal repeat sequences (ITRs), as in claim 13; [0162], rapamycin, reading on a second therapeutic molecule , as in claim 14; [0017], a ribozyme, as in claim 21; abstract, reading on autoimmune disorders such as multiple sclerosis, as in claims 23, 24; [0098], rAAV particles of e.g., AAV serotype A1, and pseudotypes, claim 26, 28; [0109, 0113], intravenous administration, as in claim 45; [0157], claim 14, preventing autoimmune disease, as in claim 48; claim 23, at least 50 days, as in claim 54; para [0009] and claim 30, at least two different neuroprotein epitopes, as in claim 57; [0185], a full-length human MOG operably linked to a hepatocyte-specific promoter, further wherein the rAAV vector is of serotype AAV8, as in claim 61.
Hoffman does not teach a sphingosine analog, as in claim 1(b).
Riedel, US 20220370470 A1, at para [0066], teaches and states:
[0066] Multiple sclerosis (MS) is a chronic inflammatory demyelinating condition that may be treated with dimethyl fumarate, fingolimod (a sphingosine-1-phosphate receptor modulator), natilizumab (Tysabri), alemtuzumab, ocrelizumab, interferons and glatirimer acetate.
Riedel, at [0055], considers “[t]he term ‘treatment’ includes ‘combination’ therapeutic treatments, in which two or more treatments to treat the relevant disease are combined, for example sequentially or simultaneously.”
It would have been prima facie obvious before the filing date of the instant application for one of ordinary skill in the art to have combined fingolimod, which is a sphingosine analog, in the method of administering a therapeutic recombinant adeno-associated viral vector encoding MBP, PLP or MOG, for treating of, e.g., an autoimmune disease such as multiple sclerosis, as in claims 1, 23 and 24.
One of ordinary skill in the art would have motivated to have combined the sphingosine analog, fingolimod, in the method of administering a therapeutic recombinant adeno-associated viral vector encoding MBP, PLP or MOG, for of treating of, e.g., an autoimmune disease such as multiple sclerosis, as in claims 1, 23 and 24, because Riedel teaches combinations treatments, such as here, where both modalities are used to treat multiple sclerosis.
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.
1. Claims 1,3,12-17,21,23,24,26,28,43,45,48,52,54,57,61 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2 of U.S. Patent No. US 12,297,444, in view of Hoffman, US 2017/0043036 A1, published Feb. 16, 2017, (of record, Serial No: 15306163) and Riedel, US 20220370470 A1, (foreign priority to GB 1909506.6, filed 2019-07-02).
US 12,297,444, in claim 2, is drawn to the rAAV vector of claim 1, wherein the first nucleic acid segment encodes a first therapeutic molecule that comprises a neuropeptide selected from a myelin basic protein (MBP), a myelin oligodendrocyte glycoprotein (MOG), and a proteolipid protein (PLP). Claim 1 recites an rAAV vector that is at least 95% identical to reference SEQ ID NOs: 16, 18, 20, 24, 26, 29, 30, 32-34, 39-42, 44-47, 49-52, 54-57, 59-62, 64-67, 69-72, 74-77, 79-82, 84-87, 89-99, 101-106, 108-113, 115-119, 121-130, 132-136, 138-142, 144-148, and 150.
At least reference claims 1 and 2, make obvious the recombinant AAV vector of instant claim 1, because the reference claims are species of the genus claim of instant claim 1.
US 12,297,444 does not claim a sphingosine analog, as in instant claim 1(b).
Hoffman teaches a method of treating a mammal in need thereof (para [0008), viral vector-based gene therapy methods for treating and/or ameliorating one or more of symptoms of autoimmune diseases, including, for example, MS.) comprising administering to the mammal a therapeutically-effective amount of: (a) a first composition comprising a recombinant adeno-associated viral (rAAV) vector comprising a polynucleotide that comprises a first nucleic acid segment that encodes a mammalian myelin basic protein (MBP), a proteolipid protein (PLP), or a myelin oligodendrocyte glycoprotein (MOG), (para [0009]), operably linked to a promoter (para [0016], [0067])that is capable of expressing the first nucleic acid segment in one or more cells of a mammalian liver (para [0132]-[0139]), hepatocyte-restricted expression of an AAV-delivered neuroantigen establishes persistent immunological tolerance mediated by antigen-specific Tregs capable of preventing and reversing EAE in mice.; [0134], Hepatic gene transfer with AAV vectors containing liver specific promoters can produce stable transgene expression and induce a robust antigen-specific immune tolerance to a variety of therapeutic proteins.; [0136], an AAV8-MOG vector was generated.; [0139], This example shows that liver directed gene transfer using an AAV vector expressing a neuro-antigen is capable of suppressing inflammation in the CNS and preventing EAE.); and (b) a second composition comprising an agent selected from an mTOR inhibitor, a sphingosine analog, a glucocorticoid, and a monoclonal antibody (para [0192], Regardless of AAV8 administration, treatment with rapamycin alone is expected to transiently produce a rapid reduction in the clinical presentation of EAE because It selectively Inhibits Teff proliferation. However, when used in conjunction with AAV8 liver gene transfer, rapamycin treatment has a synergistic effect that results in an increase in vector induced Ag-specific FoxP3+ Tregs (since they are less sensitive to mTOR signaling inhibition) with a corresponding decrease in effector T cells. The shift to tolerance is further potentiated by the fact Tregs have been shown to mediate selective inhibition of antigen-specific Th1 cells in the CNS of EAE.).
Hoffman teaches throughout the publication and at: [0137]-[0138], SEQ ID NO:1, as in claim 3; [0016], polynucleotides further comprising an enhancer, a post-transcriptional regulatory sequence, a polyadenylation signal, or any combination thereof, operably linked to the first nucleic acid segment, as claim 12; [0066], inverted terminal repeat sequences (ITRs), as in claim 13; [0162], rapamycin, reading on a second therapeutic molecule , as in claim 14; [0017], a ribozyme, as in claim 21; abstract, reading on autoimmune disorders such as multiple sclerosis, as in claims 23, 24; [0098], rAAV particles of e.g., AAV serotype A1, and pseudotypes, claim 26, 28; [0109, 0113], intravenous administration, as in claim 45; [0157], claim 14, preventing autoimmune disease, as in claim 48; claim 23, at least 50 days, as in claim 54; para [0009] and claim 30, at least two different neuroprotein epitopes, as in claim 57; [0185], a full-length human MOG operably linked to a hepatocyte-specific promoter, further wherein the rAAV vector is of serotype AAV8, as in claim 61.
Riedel, US 20220370470 A1, at para [0066], teaches and states:
[0066] Multiple sclerosis (MS) is a chronic inflammatory demyelinating condition that may be treated with dimethyl fumarate, fingolimod (a sphingosine-1-phosphate receptor modulator), natilizumab (Tysabri), alemtuzumab, ocrelizumab, interferons and glatirimer acetate.
Riedel, at [0055], considers “[t]he term ‘treatment’ includes ‘combination’ therapeutic treatments, in which two or more treatments to treat the relevant disease are combined, for example sequentially or simultaneously.”
It would have been prima facie obvious before the filing date of the instant application for one of ordinary skill in the art to have combined fingolimod, which is a sphingosine analog, in the method of administering a therapeutic recombinant adeno-associated viral vector encoding MBP, PLP or MOG, for treating of, e.g., an autoimmune disease such as multiple sclerosis, as in claims 1, 23 and 24.
One of ordinary skill in the art would have motivated to have combined the sphingosine analog, fingolimod, in the method of administering a therapeutic recombinant adeno-associated viral vector encoding MBP, PLP or MOG, for of treating of, e.g., an autoimmune disease such as multiple sclerosis, as in claims 1, 23 and 24, because Riedel teaches combinations treatments, such as here, where both modalities are used to treat multiple sclerosis.
2. Claims 1,3,12-17,21,23,24,26,28,43,45,48,52,54,57,61 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2 of copending Application No. 18191790 in view of Hoffman, US 2017/0043036 A1, published Feb. 16, 2017, (of record, Serial No: 15306163) and Riedel, US 20220370470 A1, (foreign priority to GB 1909506.6, filed 2019-07-02).
Application No. 18191790, in reference claim 2, is drawn to a recombinant adeno-associated viral (rAAV) nucleic acid vector 1. comprising: a polynucleotide that includes a nucleic acid segment that encodes a first autoimmune disease therapeutic molecule operably linked to a promoter that is capable of expressing the nucleic acid segment in one or more cells of a mammalian liver, and wherein the nucleic acid segment encodes a mammalian myelin basis protein (MBP), proteolipid protein (PLP), or myelin oligodendrocyte glycoprotein (MOG).
At least reference claim 1, make obvious the recombinant AAV vector of instant claim 1, because the reference claims are species of the genus claim of instant claim 1 in that reference claim 1 recites the limitation of a promoter for expression of the vector in liver cells, and so is a species of the more generic instant claim 1.
Application No. 18191790 does not claim a sphingosine analog, as in instant claim 1(b).
Hoffman teaches a method of treating a mammal in need thereof (para [0008), viral vector-based gene therapy methods for treating and/or ameliorating one or more of symptoms of autoimmune diseases, including, for example, MS.) comprising administering to the mammal a therapeutically-effective amount of: (a) a first composition comprising a recombinant adeno-associated viral (rAAV) vector comprising a polynucleotide that comprises a first nucleic acid segment that encodes a mammalian myelin basic protein (MBP), a proteolipid protein (PLP), or a myelin oligodendrocyte glycoprotein (MOG), (para [0009]), operably linked to a promoter (para [0016], [0067])that is capable of expressing the first nucleic acid segment in one or more cells of a mammalian liver (para [0132]-[0139]), hepatocyte-restricted expression of an AAV-delivered neuroantigen establishes persistent immunological tolerance mediated by antigen-specific Tregs capable of preventing and reversing EAE in mice.; [0134], Hepatic gene transfer with AAV vectors containing liver specific promoters can produce stable transgene expression and induce a robust antigen-specific immune tolerance to a variety of therapeutic proteins.; [0136], an AAV8-MOG vector was generated.; [0139], This example shows that liver directed gene transfer using an AAV vector expressing a neuro-antigen is capable of suppressing inflammation in the CNS and preventing EAE.); and (b) a second composition comprising an agent selected from an mTOR inhibitor, a sphingosine analog, a glucocorticoid, and a monoclonal antibody (para [0192], Regardless of AAV8 administration, treatment with rapamycin alone is expected to transiently produce a rapid reduction in the clinical presentation of EAE because It selectively Inhibits Teff proliferation. However, when used in conjunction with AAV8 liver gene transfer, rapamycin treatment has a synergistic effect that results in an increase in vector induced Ag-specific FoxP3+ Tregs (since they are less sensitive to mTOR signaling inhibition) with a corresponding decrease in effector T cells. The shift to tolerance is further potentiated by the fact Tregs have been shown to mediate selective inhibition of antigen-specific Th1 cells in the CNS of EAE.).
Hoffman teaches throughout the publication and at: [0137]-[0138], SEQ ID NO:1, as in claim 3; [0016], polynucleotides further comprising an enhancer, a post-transcriptional regulatory sequence, a polyadenylation signal, or any combination thereof, operably linked to the first nucleic acid segment, as claim 12; [0066], inverted terminal repeat sequences (ITRs), as in claim 13; [0162], rapamycin, reading on a second therapeutic molecule , as in claim 14; [0017], a ribozyme, as in claim 21; abstract, reading on autoimmune disorders such as multiple sclerosis, as in claims 23, 24; [0098], rAAV particles of e.g., AAV serotype A1, and pseudotypes, claim 26, 28; [0109, 0113], intravenous administration, as in claim 45; [0157], claim 14, preventing autoimmune disease, as in claim 48; claim 23, at least 50 days, as in claim 54; para [0009] and claim 30, at least two different neuroprotein epitopes, as in claim 57; [0185], a full-length human MOG operably linked to a hepatocyte-specific promoter, further wherein the rAAV vector is of serotype AAV8, as in claim 61.
Hoffman does not teach a sphingosine analog, as in claim 1(b).
Riedel, US 20220370470 A1, at para [0066], teaches and states:
[0066] Multiple sclerosis (MS) is a chronic inflammatory demyelinating condition that may be treated with dimethyl fumarate, fingolimod (a sphingosine-1-phosphate receptor modulator), natilizumab (Tysabri), alemtuzumab, ocrelizumab, interferons and glatirimer acetate.
Riedel, at [0055], considers “[t]he term ‘treatment’ includes ‘combination’ therapeutic treatments, in which two or more treatments to treat the relevant disease are combined, for example sequentially or simultaneously.”
It would have been prima facie obvious before the filing date of the instant application for one of ordinary skill in the art to have combined fingolimod, which is a sphingosine analog, in the method of administering a therapeutic recombinant adeno-associated viral vector encoding MBP, PLP or MOG, for treating of, e.g., an autoimmune disease such as multiple sclerosis, as in claims 1, 23 and 24.
One of ordinary skill in the art would have motivated to have combined the sphingosine analog, fingolimod, in the method of administering a therapeutic recombinant adeno-associated viral vector encoding MBP, PLP or MOG, for of treating of, e.g., an autoimmune disease such as multiple sclerosis, as in claims 1, 23 and 24, because Riedel teaches combinations treatments, such as here, where both modalities are used to treat multiple sclerosis.
This is a provisional nonstatutory double patenting rejection.
Conclusion
All claims, 1,3,12-17,21,23,24,26,28,43,45,48,52,54,57,61, are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Mark L Shibuya whose telephone number is (571)272-0806. The examiner can normally be reached M-F, 9AM-4:30PM.
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MARK L. SHIBUYA
Primary Patent Examiner
Art Unit 1631
/MARK L SHIBUYA/Primary Patent Examiner, Art Unit 1631