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 .
Response to Amendment
The Amendment filed 01/23/2026 in which claims 1, 4-6, 9, 12, were amended, and claims 3 and 17 were canceled, has been entered. Claims 18, 38, 39, 41-44 were previously withdrawn. Claims 7, 8, 13, 14, 19-37 were previously canceled.
Claims 1, 2, 4-6, 9-12, and 15-16 are under examination on the merits.
Drawings
(Previous objection, withdrawn) Applicant’s amendments to the Drawings submitted on 01/26/2023 have overcome the objection previously set forth in the Non-Final Office Action mailed 11/14/2025.
Specification
(Previous objection, withdrawn) Applicant’s amendments to the Specification submitted on 01/26/2023 have overcome the objection previously set forth in the Non-Final Office Action mailed 11/14/2025.
Claim Objections
(Previous objections, withdrawn as to claim 1). Applicant’s amendments to claim 1 have overcome previous objections to claim 1.
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.
(New rejection, necessitated by amendment as to claims 1, 2, 4-6, 9-12, and 15-16) Claims 1, 2, 4-6, 9-12, and 15-16 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.
See claims 1, 2, 4-6, 9-12, and 15-16 as submitted on 01/23/2026.
Amended claim 1 recites “(ii) a detection reagent that binds a broad array of adeno-associated virus serotypes (AAVx)”. The term “a broad array” is a relative term which renders the claim indefinite. The term is not defined by the claim, the Specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Specifically, it is not clear what is encompassed by the term “a broad array”. The dependent claims do not provide additional clarity. Therefore, the claims are indefinite. For purposes of compact prosecution and applying prior art, claim 1 was interpreted herein as reciting “(ii) a detection reagent that binds any adeno-associated virus serotypes (AAVx).”
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 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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
(Previous rejection, withdrawn as to claims 3 and 17, maintained and modified as necessitated by amendment as to claims 1, 2, 5, 6, 9-12, and 15-16). Claims 1, 2, 5, 6, 9-12, and 15-16 are rejected under 35 U.S.C. 103 as being unpatentable over Progen, in view of Zinn, et al. (prior art of record).
See claims 1, 2, 5, 6, 9-12, and 15-16 as submitted on 01/23/2026.
The previous rejections of claims 3, and 17 are moot in view of Applicant’s cancelation of these claims.
Regarding amended claim 1, it is noted that the amended claim recites “(i) a capture reagent that specifically binds an adeno-associated virus (AAVx) or an adeno-associated virus serotype 8 (AAV8), wherein the capture reagent is immobilized on a surface; and (ii) a detection reagent that binds [[an]] a broad array of adeno-associated virus serotypes (AAVx)”. The new limitations of “specifically binds” and “binds any adeno-associated virus serotypes (AAVx)” , as claim 1 is being interpreted herein (see new rejection under 35 USC § 112) are already taught by the cited prior art. Specifically 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.
However, Zinn et al. teach 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 et al. further teach the Anc80 serotype shares significant sequence homology with various known contemporary AVVs serotypes, for example AVV8 and AVV2 (pages 2-3, Fig. 2). Zinn et al. further teach 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).
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 and Zinn et al. to formulate a method for detection of the Anc80 serotype 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 vector 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 AVVs serotypes, accordingly such a method for detection of the Anc80 serotype 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).
PNG
media_image1.png
584
474
media_image1.png
Greyscale
One of ordinary skill in the art would have had reasonable expectation of success in combining the teachings of Progen and Zinn et al. 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, it is noted that no amendments were introduced to claims 2 and 5 in the amendment filed on 01/23/2026. As previously explained, 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.” 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 et al. (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, it is herein submitted that the new limitation of “a capsid protein of the Anc8” is 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.
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, it is noted that no amendments were introduced to claims 2 and 5 in the amendment filed on 01/23/2026. As previously explained, 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).
Accordingly, claims 1, 2, 5, 6, 9-12, and 15-16 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.
(Previous rejection, maintained and modified as necessitated by amendment as to claim 4). Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Progen in view of Zinn, as applied to claims 1, 2, 5, 6, 9-12, and 15-16 above, further in view of Zhu et al. (prior art of record).
See claim 4 as submitted on 01/23/2026.
Regarding claim 4, it is noted that the amended claim does not recite any new limitations. As previously explained, the claim 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, and 15-16 and taught by Progen in view of Zinn et al. above. While the embodiment of the claimed method taught by Progen in view of Zinn et al. described above teaches a detection reagent comprising biotin, the embodiment of instant claim 4 requires a capture reagent comprising biotin, not a detection reagent. Further, the embodiment of instant claim 4 requires a surface comprising streptavidin. The embodiment of instant claim 4 differs from the method taught by Progen in view of Zinn et al. in that the method taught by Progen in view of Zinn et al. teaches 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), while the embodiment of instant 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.
As indicated above, Progen in view of Zinn et al. teach a capture or sandwich ELISA method for detection of Anc80 AAV.
Neither Progen nor Zinn et al. teach an embodiment wherein the capture reagent comprises biotin, and the surface comprises avidin or streptavidin.
However, Zhu et al. teach 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 et al. further teach 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 et al. and Zhu et al. to formulate a method for detection of the Anc80 serotype 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 et al., and Zhu et al. 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
Applicant's arguments filed 01/23/2026 have been fully considered but they are not persuasive.
Applicant contends on page 8 of the Remarks submitted on 01/23/2026:
“Progen only describes an ELISA in which an antibody that specifically binds AAV8 is used as both the capture reagent and the detection reagent, for the specific purpose of detecting AAV8. Progen does not provide any motivation or rationale for one of ordinary skill in the art to modify its ELISA by replacing the biotin-conjugated anti-AAV8 antibody used in detection with "a detection reagent that binds a broad array of adeno-associated virus serotypes" as featured in the present claims, in order to detect Anc80.
In fact, one of ordinary skill in the art reading the cited references would have simply used Progen's ELISA as-is, without any modifications, to detect Anc80 in view of the description in Zinn that Anc80 shares "significant sequence homology" with AAV8. See Zinn at p. 1057, col. 2, last para., and OA at p. 7, second para. One of ordinary skill in the art therefore would have recognized that an ELISA using anti-AAV8 antibodies, as described in Progen, would have been capable of detecting Anc80 and therefore would not have modified Progen's ELISA to utilize the combination of an anti-AAV8-specific capture reagent and "a detection reagent that binds a broad array of adeno-associated virus serotypes," in a method to detect Anc80 as featured in the present claims. Accordingly, one of ordinary skill in the art reading the cited references would not have arrived at the presently claimed method based on Progen and/or Zinn.
In response:
The instant rejection is in view of instant claim language. The recitation of "a detection reagent that binds a broad array of adeno-associated virus serotypes" renders claim 1 indefinite for the reasons explained above. The new limitations of a detection reagent that binds any adeno-associated virus serotypes is encompassed by the teachings of Progen, which comprise binding to an AAV8. Further, as noted previously and above, that instant Application refers to the same exact antibody clone, namely ADK8 (Specification ¶¶ [0055], [0058], [0070], [0072] as Progen). 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. 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.
The cited prior art teaches the exact embodiment instantly claimed as well as clear motivations and rationale to arrive at the claimed invention with reasonable expectation of success, as explained above in detail. For example, as noted above, Zhu et al. teach a method with streptavidin-coated plated 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). Accordingly, the Remarks presented fail to provide evidence of nonobviousness to overcome the rejections of record.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARLENE V BUCKMASTER whose telephone number is (703)756-5371. The examiner can normally be reached M-F 8-5.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Thomas J Visone can be reached at (571) 270-0684. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/MARLENE V BUCKMASTER/Examiner, Art Unit 1672
/THOMAS J. VISONE/ Supervisory Patent Examiner, Art Unit 1672