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 foreign priority under 35 U.S.C. 119
(a)-(d). Acknowledgment is made of Applicants’ claim for benefit to foreign application PCT/CN2020/129001 filed 11/16/2021. This application claims the benefit of priority to Patent Application PCT/CN2021/130784. Acknowledgement is made of Applicants’ claim for benefit to prior filed to Patent Application Number PCT/CN2021/130784, filed on 11/16/2021.
Information Disclosure Statement
The Information Disclosure Statements filed 05/09/2023, 10/23/2024, and 07/25/2025 have been considered by the Examiner.
Status of Claims
Claims 1-16 and 18-23 are under examination.
Claims 17, and 24-33 are canceled.
Claim Objections
Claims 13-15 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
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 1-10, 16, 18-23, are rejected under 35 U.S.C. 103 as being unpatentable over Miller (WO2020/117898 A1) and in further view of Xiao et al. (US 8,632,764) and as evidenced by Liu et al (CN101906417A).
Regarding claim 1, Miller teaches a recombinant adeno-associated virus (rAAV) comprising (a) an adeno associated virus with a capsid protein (page 1, paragraph 0004) and (b) an expression cassette comprising a polynucleotide sequence, which encodes a therapeutic agent useful in treating and preventing liver disease related conditions (page 38, paragraph 00148).
Miller does not teach the capsid protein having an amino acid sequence of SEQ ID NO:1.
Xiao et al. teach a recombinant adeno-associated virus (rAAV) comprising an adeno-associated virus (AAV) capsid protein. Xiao et al. teach the AAV vectors comprises capsids generated by scrambling capsid sequences from two or more of the following: AAV1, AAV2, AAV3A, AAV3B, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, AAV10, AAV11, AAV12 (column 49, lines 31-36). Xiao et al. teach improved evasion as compared to AAV2 and AAV8 serotypes allowing the vector to reach and transduce target tissue (column 49, lines 14-21). Xiao et al. teach the capsid protein having the amino acid sequence of SEQ ID NO:30 (which is the same as SEQ ID NO:1) (figure 3RR).
It would have been obvious to one of ordinary skill in the art at the time the invention was made to have combined the teachings of Miller for an adeno associated virus vector for treating and preventing liver disease with the teachings of Xiao et al. for a capsid protein having an amino acid sequence of SEQ ID NO:30 (which is the same as SEQ ID NO:1). Xiao et al. provide motivation by teaching that mosaic or "scrambled" AAV capsids are useful for various properties including tropism or neutralization (cover page, abstract). Xiao et al. further provide motivation teaching the mosaic provide the ability to evade neutralizing antibodies. One of skill in the art would have had a reasonable expectation of success at combining Miller and Xiao et al. because they both teach rAAV vectors for treating tissues.
Regarding claim 2, Miller and Xiao et al. make obvious the vector as described above in regard to claim 1. Miller teaches the therapeutic agent could be alpha galactosidase (GLA) (page 32, paragraph 00128).
Regarding claim 3, Miller and Xiao et al. make obvious the vector as described above in regard to claim 1. Miller teaches the promoters operatively linked to the downstream sequence (page 9, paragraph 0057).
Regarding claim 4, Miller and Xiao et al. make obvious the rAAV described above in regard to claim 3. Xiao et al. teach an expression construct driven by a CMV promoter or a pol II promoter (column 23, lines 63-66). Xiao et al. further teach a variety of promoter/enhancer elements may be used depending on the level and tissue-specific expression desired (column 26, lines 35-38). Xiao et al. teach the use of pol II promoters in tissue specific expression applications (column 23, lines 63-66).
Regarding claim 5, Miller and Xiao et al. make obvious the rAAV of claim 3 as described above. Miller teaches the promoter is a U6, H1, or 7SK (page 10, paragraphs 0059&0060).
Regarding claim 6, Miller and Xiao et al. make obvious the rAAV as described above in regard to claim 3. Miller teaches an H1 promoter for the heterologous sequence. Miller teaches the heterologous sequence can encode RNAi (page 73, claim 15), which can be shRNA as further taught in Xiao et al. (column 20, lines 41-44).
Regarding claim 7, Miller and Xiao et al. make obvious the rAAV described above in regard to claim 1. Miller teaches the rAAV includes two inverted terminal repeat sequences (ITR) (page 28, paragraph 00117).
Regarding claim 8, Miller and Xiao et al. make obvious the rAAV described above in regard to claim 7. Xiao et al. further teach the AAV terminal may be from any AAV including serotypes 1, 2, 3, 4, 5, 6, 7, 8, 9 or any other AAV now know nor later discovered (column 14, lines 41-45).
Regarding claim 9, Miller and Xiao et al. make obvious the rAAV described above in regard to claim 7. Xiao et al. further teach the AAV terminal is derived from an AAV2 serotype (column 14, lines 41-45).
Regarding claim 10, Miller and Xiao et al. make obvious the rAAV as described above in regard to claim 2. Miller et al. teach the GLA comprises SEQ ID NO: 149 which is SEQ ID NO: 2 of the present application (page 35, Table 4).
Regarding claim 16, Miller and Xiao et al. make obvious the rAAV described above in regard to claim 1. Miller further teaches a pharmaceutical composition comprising a vector and a pharmaceutically acceptable carrier and diluent (pages 18&37, paragraph 0085&00144).
Regarding claim 18, Miller and Xiao et al. make obvious the rAAV described above in regard to claim 1. Xiao et al. teach a method of treating diseases related to hepatitis in a patient in need thereof (column 20, lines 33-35). Hepatitis B virus (HBV) causes liver disease as evidenced by Liu et al. (page 3, Background technique), therefore the method of Xiao et al. treats a patient with liver disease.
Regarding claim 19, Miller and Xiao et al. make obvious the method as described above in regard to claim 18. Miller et al. teach the disease is Fabry disease (page 38, paragraph 00148). Xiao et al. further teach the rAAV can be used for treatments of Fabry disease or Hepatitis B (column 35, lines 19-31).
Regarding claim 20 Miller and Xiao et al. make obvious the method as described above in regard to claim 18. Xiao et al. teach the nucleic acid is delivered by intravenous administration (column 38, lines 45-50).
Regarding claim 21, Liu et al. and Xiao et al. make obvious the method as described above in regard to claim 18. Xiao et al. teach particular embodiments, the present invention provides a pharmaceutical composition comprising a virus vector and other medicinal or pharmaceutical agents (column 41, lines 37-40).
Regarding claim 22, Miller and Xiao et al. make obvious the method as described above in regard to claim 18. (i) Miller teaches increased level of GLA expression in liver tissue of all samples transduced (page 53, paragraph 00200). Xiao et al. teach improved evasion as compared to AAV2 and AAV8 serotypes allowing the vector to reach and transduce target tissue (column 49, lines 14-21). Xiao et al. do not directly compare the expression to a corresponding rAAV comprising an AAV2/8 serotype capsid protein, however the capsid is the same as the present invention it would inherently provide the same improvement over an AAV2/8 serotype when tested.
(ii) Xiao et al. teach administration of the rAAV results in expression of the inhibitory RNA in the target cell diminishes expression of a particular protein or proteins by the cell. Xiao et al. teach inhibitory RNA may be administered to decrease expression of a particular protein in a subject in need thereof. Inhibitory RNA may also be administered to cells in vitro to regulate cell physiology to optimize cell or tissue culture systems (column 39, lines 17-26). Xiao et al. do not directly compare the expression to a corresponding rAAV comprising an AAV2/8 serotype capsid protein, however the capsid is the same as the present invention it would inherently provide the same improvement over an AAV2/8 serotype when tested.
Regarding claim 23, Miller and Xiao et al. make obvious the method as described above in regard to claim 18. Miller teaches treatment with a therapeutically effective amount of the rAAV (page 38, paragraph 00146). Miller teaches the therapeutically effective amount of the rAAV is from 109 vector genomes to as much as 1017 vector genomes per administration. (page 42, paragraph 00163). Miller reads on the 1x106 VG to about 1x1018 VG because the amount falls within the range. One of ordinary skill in the art would perform routine experimentation to determine the therapeutically effective amount of rAAV.
Claims 11 and 12 are rejected under 35 U.S.C. 103 as being unpatentable over Miller (WO2020/117898 A1) in view of Xiao et al. (US 8,632,764) as applied to claims 1 and 3 above, and further in view of Sætrom et al. (US 2018/0305689 A1).
Regarding claim 11, Miller and Xiao et al. make obvious the rAAV of claim 3.
Miller and Xiao et al. do not teach the human non-encoding filler sequence.
Sætrom et al. teach short RNAs to regulate transcription by disrupting non-coding transcripts (page 1, paragraph 0005). Sætrom et al. teach the addition of a human HPRT-intron sequence (page 30, paragraph 0100). Sætrom et al. teach compositions for modulating target gene expression for diagnostic and therapeutic applications (page 1, paragraph 0004). Sætrom et al. teach delivery of the saRNA by an AAV vector (page 85, paragraph 0225).
It would have been obvious to one of ordinary skill in the art at the time the invention was made to have combined the teachings of Miller and Xiao et al. a recombinant adeno-associated virus comprising an engineered capsid protein and a promoter operably linked to the downstream sequence with the teachings of Sætrom et al. for inclusion of a human HPRT-intron sequence. Sætrom et al. provide motivation by teaching that non-coding RNAs can modulate target gene expression for diagnostic and therapeutic applications. One of skill in the art would have had a reasonable expectation of success at combining Miller, Xiao et al. and Sætrom et al. because they teach delivery of therapeutics via an AAV vector.
Regarding claim 12, Miller, Xiao et al. and Sætrom et al. make obvious the rAAV of claim 11. Sætrom et al. further teach the human non-encoding sequence is an HPRT-intron sequence comprising SEQ ID NO:1563730 which is the same as SEQ ID NO:4 of the present application.
Conclusion
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/C.L.M./Examiner, Art Unit 1638
/Anna Skibinsky/
Primary Examiner, AU 1635