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 .
Priority
Acknowledgment is made of applicant’s claim for priority based on a provisional application filed as 63/046,211 on 06/30/2020.
All claims are given the priority date of 06/30/2020.
Application Status
Receipt is acknowledged of amendment, filed 07/01/2024. Claims 1-14, 16, 24, 25, 31, 34 and 36 are currently pending.
Election/Restriction
Applicant’s election without traverse of Group II, drawn to claims 6-14, 16, 24, 25, 31, 34 and 36, in the reply filed on 07/01/2024 is acknowledged.
Claims 1-5 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 07/01/2024.
Claims 6-14, 16, 24, 25, 31, 34 and 36 are currently under examination.
Information Disclosure Statement
Receipt of acknowledgment of the information disclosure statement filed on 12/21/2022 have been received and all references have been considered.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01. Specifically, hyperlinks are found at paragraphs [0066] and [0117].
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.
Claims 6-14, 16, 31, 34 and 36 are rejected under 35 U.S.C. 103 as being unpatentable over Roeth et al (US 2013/0195800 A1) in view of MacLaren (US 2016/0206704 A1).
Regarding claims 6-10 and 31, Roeth teaches the AAV vector and methods of the present invention can be used to treat a cancer, specifically glioblastoma [0545 and 0577]. Roeth teaches an AAV vector for expressing proteins having the functions of one or more therapeutic proteins wherein the therapeutic protein (e.g., immunomodulator) is selected from IFN-alpha, IFN-gamma and/or IFN-beta wherein the therapeutic proteins are under the control of a promoter, specifically a CMV promoter [0015-0016, 0545 and 0555]. Roeth teaches a method for treating a tumor in a mammal, comprising the steps of: (a) administering vectors of the invention (or a combination thereof), which are in vitro engineered to conditionally express one or more proteins having the function of a therapeutic protein (e.g., immunomodulator) [0030-0031].
Roeth does not specifically teach the CAG promoter as outlined in the instant claims.
MacLaren teaches a gene therapy including a promoter and transgene wherein the promoter is a CAG promoter with a transgene encoding a cytokine [0192]. MacLaren teaches the CAG promoter which comprises in the 5’ to 3’ direction: i) s cytomegalovirus (CMV) enhancer sequence, ii) a chicken beta-actin (CBA) gene promoter element, iii) a spacer sequence and iv) a rabbit beta-globin splice acceptor as SEQ ID NO: 5 which is 100% identical to instant SEQ ID NO: 6 (See Appendix I). It is noted that instant SEQ ID NOs: 1-4, in that order, make up instant SEQ ID NO: 6. Furthermore, SEQ ID NO: 5 of MacLaren shows 100% identity to instant SEQ ID NOs: 1-4 in the respective numerical order and does not include instant SEQ ID NO: 5 (See Appendices II-VI).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute the generic CMV promoter of Roeth for the CAG promoter as taught by MacLaren because Roeth teaches it is within the ordinary skill in the art to use a vector for expressing proteins having the functions of one or more therapeutic proteins wherein the therapeutic protein (e.g., immunomodulator) is selected from IFN-alpha, IFN-gamma and/or IFN-beta wherein the therapeutic proteins are under the control of a promoter, specifically a CMV promoter and MacLaren teaches a gene therapy including a CAG promoter and transgene wherein the promoter is a CAG promoter with a transgene encoding a cytokine.
Because both Roeth and MacLaren teach using a promoter with a transgene encoding a cytokine for the purpose of administration to a cell for treatment, it would have been obvious to one skilled in the art to substitute one promoter for the other to achieve the predictable result of transgene expression. Thus, substitution of the CMV promoter of Roeth, for the CAG promoter of MacLaren would have been prima facie obvious to one of ordinary skill in the art, and thus the invention as claimed is unpatentable over the work of the prior art. Substitution of one known method for another known method, the methods having equivalent effect, is considered to be obvious, absent a showing that the result of the substitution yields more than predictable results. See MPEP 2143(I)(B).
Regarding claims 11, 12, 14 and 16, Roeth teaches an AAV vector for expressing proteins having the functions of one or more therapeutic proteins wherein the therapeutic protein (e.g., immunomodulator) is selected from IFN-alpha, IFN-gamma and/or IFN-beta wherein the therapeutic proteins are under the control of a promoter, specifically a CMV promoter [0015-0016, 0545 and 0555]. Roeth teaches a polynucleotide encoding one or more proteins having the function of a therapeutic protein (e.g., immunomodulator) operably linked to a promoter, wherein the one or more therapeutic proteins (e.g., immunomodulators) are selected from human IFN-gamma, human IFN-alpha 1 and human IFN-beta ([0074, 0142, 0144] and Page 49, Table 6). Roeth teaches IFN-gamma is a potent activator of macrophages, it has antiproliferative effects on transformed cells and it can potentiate the antiviral and antitumor effects of the type I interferons (Page 49, Table 6). Roeth teaches IFN-beta is a member of group of interferon proteins that bind to specific cell surface receptors (IFNAR), and stimulates both macrophages and natural killer (NK) cells to elicit an antiviral, antibacterial and anticancer activities (Page 49, Table 6). Roeth teaches IFN-alpha has anti-tumor function (Page 49, Table 6).
One of ordinary skill in the art would have been further motivated to incorporate the basic design of combining one or more of the interferon genes in any combination under the control of the promoter as taught by Roeth in paragraphs [0015-0016, 0074, 0142, 0144, 0545 and 0555] in order to reach the claimed order of the combined interferon genes. See MPEP§ 2143.01.
Regarding claim 13, Roeth teaches the gene encoding an immunomodulator is codon-optimized for expression in human [0512].
Regarding claims 34 and 36, Roeth teaches the AAV vector and methods of the present invention can be used to treat a cancer, specifically glioblastoma [0545 and 0577]. Roeth teaches an AAV vector for expressing proteins having the functions of one or more therapeutic proteins wherein the therapeutic protein (e.g., immunomodulator) is selected from IFN-alpha, IFN-gamma and/or IFN-beta wherein the therapeutic proteins are under the control of a promoter, specifically a CMV promoter [0015-0016, 0545 and 0555]. Roeth teaches a method for treating a tumor in a mammal, comprising the steps of: (a) administering vectors of the invention (or a combination thereof), which are in vitro engineered to conditionally express one or more proteins having the function of a therapeutic protein (e.g., immunomodulator) into a mammalian cell [0030-0031 and 0567].
Claims 24 and 25 are rejected under 35 U.S.C. 103 as being unpatentable over Roeth et al (US 2013/0195800 A1) in view of MacLaren (US 2016/0206704 A1), as applied to claims 6-14, 16, 31, 34 and 36 above, and further in view of Liu et al (Sci Rep 7, 2193 (2017); Pgs. 1-9).
The teachings of Roeth and MacLaren are described above and applied as before.
Regarding claims 24 and 25, Roeth and MacLaren do not teach self-cleaving peptides in between the transgenes encoding the hIFN-α1, hIFN-β and hIFN-γ.
Liu teaches the cloning of multiple genes in a single vector has greatly facilitated both basic and translational studies that require co-expression of multiple factors or multi-units of complex protein, specifically, using 2A “self-cleaving” peptides have garnered increased interest for their polycistronic nature, small size and high “cleavage” efficiency (Page 1, Abstract). Liu teaches tri-cystronic constructs where each 2A “self-cleaving” peptides are placed between in between each gene for expression (Page 4, Fig. 3A). Liu teaches the use of 2A “self-cleaving” peptides generally provided high-efficiency and co-regulated multi-gene expression, however, using two different 2A “self-cleaving” in the tri-cystronic construct, specifically P2A and T2A, generally exhibit the highest cleavage efficiency (Page 4, Paragraph 2).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of Roeth and MacLaren to include the 2A self-cleaving peptides in between each transgene as taught by Liu because Roeth teaches it is within the ordinary skill in the art to use a vector for expressing proteins having the functions of one or more therapeutic proteins wherein the therapeutic protein (e.g., immunomodulator) is selected from IFN-alpha, IFN-gamma and/or IFN-beta wherein the therapeutic proteins are under the control of a promoter, specifically a CMV promoter, MacLaren teaches a gene therapy including a CAG promoter and transgene wherein the promoter is a CAG promoter with a transgene encoding a cytokine and Liu teaches the use of 2A “self-cleaving” peptides in between genes within a multi-gene co-expression vector generally provided high-efficiency and co-regulated multi-gene expression, however, using two different 2A “self-cleaving” in the tri-cystronic construct, specifically P2A and T2A, generally exhibit the highest cleavage efficiency.
One would have been motivated to make such a modification in order to receive the expected benefit of multi-gene expression with increased efficiency within a single expression construct as taught by Liu.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALEXANDRA ROSE LIPPOLIS whose telephone number is (703)756-5450. The examiner can normally be reached Monday-Friday, 8:00am to 5:00pm EST.
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/ALEXANDRA ROSE LIPPOLIS/Examiner, Art Unit 1637
/CELINE X QIAN/Primary Examiner, Art Unit 1637
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