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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 06/01/2026 has been entered.
Claim Rejections - 35 USC § 112
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.
Claim 6 is 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 6 recites the limitation " The method of claim 1, wherein the capture reagent binds to a capsid protein of the Anc8.” There is insufficient antecedent basis for “the Anc 8” limitation in the claim. For purposes of compact prosecution, “Anc 8” is understood as “Anc80.”
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.
Claims 1, 2, 5, 6, 9-12, 15-16, and 45 are rejected under 35 U.S.C. 103 as being unpatentable over Progen (Progen AAV8 Titration ELISA Manual, 2018), in view of Zinn et al (Cell Rep, 2016, 10.1016/j.celrep.2015.07.019, hereinafter, “Zinn”) and Mietzsch (Hum Gene Ther, 2013, 10.1089/hum.2013.184, hereinafter, “Mietzsch”).
Progen teaches a method for detecting adeno-associated virus in a sample comprising a capture or sandwich ELISA technique and using the anti-AVV8 antibody ADK8 (page 1). The method of Progen comprises the following steps:
Contacting the sample with a capture reagent comprising an antibody that specifically binds an adeno-associated virus serotype 8 (AAV8) (pages 1, 4, illustration step 1), wherein the capture reagent is immobilized on the surface of the wells of a multi-well plate such as a 96-well plate (pages 1, 2, 4 illustration step 1). As noted previously, Progen teaches the capture reagent is a mouse monoclonal antibody against an AAV8 termed clone ADK8 which is the same exact antibody clone instant Application, (Specification ¶¶ [0055], [0058], [0070], [0072])
Contacting the sample with a detection reagent comprising an antibody that binds an adeno-associated virus (pages 1, 2, 4, illustration step 2)
Forming a binding complex comprising the capture reagent, the adeno-associated virus in the sample, and the detection reagent (pages 1, 4 illustration step 2)
Detecting the binding complex, thereby detecting the adeno-associated virus in the sample (pages 1, 2, 4 illustration step 6)
Progen does not explicitly teach detection of adeno-associated virus (AVV) serotype Anc80 in the sample, nor does Progen explicitly teach ADK8, the detection reagent, is capable of binding to more than one AAV serotype (AAVx), or the explicit use of cell lysate.
However, Mietzsch teaches scalable and genetically stable AAV production systems (Abstract). Mietzsch teaches the high titer production of AAV serotypes 1 – 12 (Abstract). Mietzsch teaches the identification of AAVx using a series of antibodies specific for conformational epitopes present on the surfaces of intact AAV capsids (Section: Integrity of AAV capsids produced in Sf9 cells, Figure 3). Regarding claim 1, Mietzsch teaches that the ADK8 antibody binds to multiple AAVx (Figure 3, reproduced below). Importantly, ADK8 is the same antibody clone recited in the instant Application as well as the same antibody taught by Progen. Importantly, the instant application defines both the capture reagent and detection reagent as ADK8 (¶0055 – “In some embodiments, the capture reagent is AAV8 antibody clone ADK8.”; ¶0058 – “In some embodiments, the detection reagent is AAV8 antibody clone ADK8.)
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Furthermore, Zinn teaches an ancestral adeno-associated virus (AVV) termed Anc80 from which most known contemporary AAVs evolved. The Anc80 serotype was reconstructed by performing ancestral sequence reconstruction (ASR) methods (Abstract, pages 1-3, Fig. 1). Zinn further teaches the Anc80 serotype shares significant sequence homology with various known contemporary AVVs serotypes, for example AVV8 and AVV2 (pages 2-3, Fig. 2). Zinn further teaches the Anc80 serotype is highly stable and can be produced efficiently making it a highly potent vector particle with potential use in gene therapy applications (pages 9-11).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date to have combined the teaching of Progen, Zinn, and Mietzsch to formulate a method for detection of the multiple Anc80 serotypes for the advantage of detecting the presence of Anc80-based vectors used in gene therapy applications in a sample. One of ordinary skill in the art would have been motivated to formulate such a detection method to confirm efficient transduction of an Anc80-based vectors used for delivering a gene into a host cell. Further motivation derives from the sequence homology that the Anc80 serotype shares with various known contemporary AVV serotypes, accordingly such a method for detection of the Anc80 serotypes would also serve to confirm the presence of various known contemporary AVVs serotypes with which the Anc80 serotype shares sequence homology. See MPEP 2144.07. The selection of a known material based on its suitability for its intended use supported a prima facie obviousness determination in Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945).
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One of ordinary skill in the art would have had reasonable expectation of success in combining the teachings of Progen, Zinn, and Mietzsch given that the methods of formulating immunoassays such as a capture or sandwich ELISA for detection of AVVs are well known, successfully demonstrated, and commonly used as evidenced by the applied prior art.
Regarding claims 2 and 5, Progen further teaches the capture reagent is an antibody against an AAV8 which is immobilized on the surface of the wells of a multi-well plate such as a 96-well plate (pages 1, 2, 4 illustration step 1).
Regarding amended claim 6, the claims recite “a capsid protein of the Anc8.” As discussed above, claim 6 is interpreted as “a capsid protein of the AAV8.” It is noted that Progen already teaches binding to a conformational epitope on the capsid protein of the AAV8 (page 1). Again, given the significant sequence homology Anc80 serotype shares with various known contemporary AVVs serotypes, for example AVV8 taught by Zinn (pages 2-3, Fig. 2) and the fact that Progen teaches the same exact antibody clone (ADK8) as the one used in instant Application, (Specification ¶0055, 0058, 0070, 0072); absent evidence to the contrary, the limitation of “a capsid protein of the Anc8” is considered to be an inherent property of the ADK8 antibody. See MPEP 2112.01. I. When the structure recited in the reference is substantially identical to that of the claims, claimed properties or functions are presumed to be inherent.
Regarding claims 9-12, as indicated above Progen teaches the capture reagent and a detection reagent, both are a mouse monoclonal antibody against an AAV8 termed clone ADK8 (page 1). Again, it is noted that instant Application refers to the same exact antibody clone, namely ADK8 (Specification ¶0055, 0058, 0070, 0072). The epitope to which said antibody clone ADK8 binds is an inherent property which is necessarily present due to conservation of critical structural elements, namely the antibody’s complementary determining regions (CDRs) sequences themselves. While Progen does not explicitly teach the capture reagent binds to VP3 of Anc80 (as recited in amended claim 9), the capture reagent binds to an epitope within residues 580 to 600 of VP3 (as recited in instant claim 10) the capture reagent binds to LQSANT (SEQ ID NO:1) (as recited in instant claim 11) and the detention reagent binds to a capsid protein of the Anc80 (as recited in claim 12); these limitations are considered to be inherent properties of the ADK8 antibody. See MPEP 2112.01. I. When the structure recited in the reference is substantially identical to that of the claims, claimed properties or functions are presumed to be inherent. Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. “Products of identical chemical composition can not have mutually exclusive properties.” In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present.
Regarding claims 15 and 16, Progen further teaches the detection reagent is an antibody against an AAV8 which comprises a biotin binding partner of a detectable moiety comprising streptavidin conjugated to horseradish peroxidase (HRP) (pages 1, 2, 4 illustration steps 3 and 4).
Regarding claim 45, Mietzsch teaches a sample of purified cell lysate (Section: rAAV production in 293 cells, Figure 3).
Accordingly, claims 1, 2, 5, 6, 9-12, 15-16, and 45 were prima facie obvious to one of ordinary skill in the art before the effective filing date, especially in the absence of evidence to the contrary.
Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Progen in view of Zinn and Mietzsch, as applied to claims 1, 2, 5, 6, 9-12, 15-16 and 45 above, further in view of Zhu et al. (J Translational Medicine, 2014, 10.1186/s12967-014-0352-5, hereinafter, “Zhu”).
Claim 4 recites “wherein the capture reagent comprises biotin, and the surface comprises avidin or streptavidin.” It is noted that this recitation encompasses an embodiment of the claimed method that differs from the method as recited in claims 1, 2, 5, 6, 9-12, 15-16, and 45 taught by Progen in view of Zinn and Mietzsch above.
While the references teach a detection reagent comprising biotin, claim 4 requires a capture reagent comprising biotin. Furthermore, claim 4 requires a surface comprising streptavidin. While claim 4 requires that the surface of the wells to be coated with streptavidin which binds to biotin in the capture reagent thereby immobilizing the capture reagent, Progen, Zinn, and Mietzsch teach streptavidin conjugated to HRP as part of a detectable moiety that is added after the formation of the binding complex (Progen, pages 1, 2, 4 illustration steps 1-4).
As indicated above, Progen, Zinn, and Mietzsch teach a capture or sandwich ELISA method for detection of Anc80 AAV.
However, Zhu teaches a method of capture of sandwich ELISA for detection of viral particles, wherein the capture reagent comprises biotin, and the surface of the wells of the testing plate comprises streptavidin (Abstract, pages 1-3, Fig. 1). Zhu further teaches such a method offers greater sensitivity than that of a conventional capture or sandwich ELISA because the high density of streptavidin on the surface of wells can bind more biotinylated capture reagent and the binding of biotin to streptavidin is highly resistant to some severe environments such as organic solvents, proteolytic enzymes and extremes of temperature and pH (pages 8, 9).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date to have combined the teaching of Progen, Zinn, Mietzsch, and Zhu to formulate a method for detection of multiple Anc80 serotypes wherein the capture reagent is immobilized onto the surface of wells by the binding of biotin to streptavidin for the benefit of detecting the presence of Anc80-based vectors used in gene therapy applications in a sample with greater sensitivity. See MPEP 2144.07. The selection of a known material based on its suitability for its intended use supported a prima facie obviousness determination in Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945).
One of ordinary skill in the art would have had reasonable expectation of success in combining the teachings of Progen, Zinn, Mietzsch, and Zhu given that the methods of formulating immunoassays such as a capture or sandwich ELISA for detection of AVVs wherein the capture reagent if immobilized by the binding of biotin to streptavidin are well known, successfully demonstrated, and commonly used as evidenced by the applied prior art.
Accordingly, claim 4 was prima facie obvious to one of ordinary skill in the art before the effective filing date, especially in the absence of evidence to the contrary.
Response to Arguments
1) Applicant states amendments to claim 1 overcome the previous rejection detailed in the Office Action mailed 03/09/2026. Applicant states the ADK8 antibody used by Progen “specifically binds AAV8” and that Progen uses ADK8 as both the capture reagent and the detection reagent.
As discussed above, ADK8 does not bind exclusively to AAV8 (see Mietzsch figure 3 reproduced above). ADK8 binds to AAV 1, 3, 7, 8, and AAVrh.10. Furthermore, the claims reasonably encompass ADK8 as both the capture reagent and detection reagent. As evidenced by the Specification: (¶0055 – “In some embodiments, the capture reagent is AAV8 antibody clone ADK8.”; ¶0058 – “In some embodiments, the detection reagent is AAV8 antibody clone ADK8”). Zinn teaches AAV8 has significant homology with Anc80. Thus, as discussed above, Progen, Zinn, and Mietzsch reasonably teach a capture agent that binds to AAV8 and a detection reagent that is capable of binding more than one AAVx that form a binding complex comprising the capture reagent, Anc80, and the detection reagent. Therefore, taken together Progen, Zinn, and Mietzsch render claim 1 prima facie obvious.
Conclusion
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/DANYAL HASSAN ALAM/Examiner, Art Unit 1672
/THOMAS J. VISONE/Supervisory Patent Examiner, Art Unit 1672
