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 .
Status of Application/Amendment/Claims
This Office action is in response to the communications filed on April 30, 2026.
Currently, claims 1, 3-4, 9-10, and 19-24 are pending in the instant application. Claim 10 is withdrawn from further consideration as being drawn to a nonelected invention. Accordingly, claims 1, 3-4, 9, and 19-24 are under examination on the merits in the instant application.
The following rejections are either newly applied or are reiterated and are the only rejections and/or objections presently applied to the instant application.
Response to Arguments and Amendments
Withdrawn Rejections
Any rejections/objections not repeated in this Office action are hereby withdrawn.
Maintained Rejections
Claim Rejections - 35 USC § 112
Claims 1, 3-4, and 9 remain rejected under 35 U.S.C. 112(a) as failing to comply with the written description requirement for the reasons as set forth in the Office action mailed on January 21, 2026 and for the reasons stated below.
Applicant's arguments filed on April 30, 2026 have been fully considered but they are not persuasive. Applicant argues that the claims as amended comply with the written description by pointing out pages 3 and 12 of the specification. Contrary to applicant’s argument, the pages pointed out by applicant at best provide a generic, prophetic disclosure without any adequate, sufficient support that the instantly claimed combination method comprising co-administering plerixafor, an AAVR inhibitor, and an AAV gene therapy vector achieves increased AAV gene transfer to cells other than the liver and/or decreased AAV liver toxicity in a subject, especially when all three are co-administered “simultaneously” or “at the same time”. The disclosure at pages 3-4 of the specification that “mobilization of these [HSC] cells will increase the exposure of these cells to AAV vectors administered in vivo” does not whatsoever describe in sufficient detail that the claimed method that co-administers plerixafor results in the increased AAV gene expression in non-liver cells or reduces AAV liver toxicity or plays any functional role in reducing AAV liver toxicity.
Regarding claim 9, page 11 of the specification at best discloses that the gene therapy vector “comprises the addition of CD47 on the surface of the viral vector” “for reducing the elimination of viral vectors in vivo”. Hence, CD47 on the surface of the AAV gene therapy vector appears to have nothing to do with the claimed effects of increasing AAV gene transfer to non-liver cells and decreasing AAV liver toxicity. Furthermore, there is no adequate, sufficient written description support at pages 11-12 or any other pages of the specification that co-administration of plerixafor, an AAVR inhibitor, and an AAV gene therapy vector comprising CD47 on the surface leads to the claimed, required effects in the claimed subject. Most importantly, there is no disclosure that reasonably conveys that the instant co-inventors had possession of the rejected claims as of the filing date as evidenced by the fact that the specification’s disclosure at best amounts to a mere conjecture or academic hypothesis, which has not been shown to actually work. In fact, applicant’s assertion that “the use of CD47 allows the AAV vector more opportunity to infect non-liver cells – particularly when used in combination with the administration of an AAVR inhibitor to the liver” is not adequately supported/described by the instant specification or by the prior art knowledge, thereby amounting to mere academic theories/conjectures.
“Patents are not awarded for academic theories, no matter how groundbreaking or necessary to the later patentable inventions of others. “[A] patent is not a hunting license. It is not a reward for the search, but compensation for its successful conclusion.” Id. at 930 n.10 (quoting Brenner, 383 U.S. at 536). Requiring a written description of the invention limits patent protection to those who actually perform the difficult work of “invention” – that is, conceive of the complete and final invention with all its claimed limitations – and disclose the fruits of that effort to the public.” (emphasis added). Ariad Pharmaceuticals Inc. v. Eli Lilly & Co, 598 F3d 1336, 1173-1174, 94 USPQ2d 1161 (Fed. Cir. 2010).
In the instant case, there is no disclosure in the specification that shows that the instant co-inventors did “actually perform the difficult work of “invention”” and “disclose the fruits of that effort to the public” in order to comply with the written description requirement under 35 U.S.C. 112(a). There is simply no “successful conclusion” of the merely disclosed “academic theories”, for which patents are not awarded. The disclosure pertaining to two injections of an anti-LDLR antisense oligonucleotide with the resultant effect of inhibiting LDLR expression in the liver of the injected mice (see page 22) is a far cry from adequately describing the instantly claimed combination co-administration method in a manner to reasonably convey that the instant co-inventors did “actually perform the difficult work of “invention”” and disclosed “successful conclusion” and “fruits of the that effort”. As such, the instant specification including the disclosure at page 22 pertaining to the mere antisense-mediated inhibition of LDLR expression in the liver is deficient in adequately describing the claimed method in such as manner to reasonably convey that the instant co-inventors had possession of the claimed subject matter as of the filing date sought in the instant case.
In view of the foregoing, this rejection is maintained.
New Rejections Necessitated by Amendment
Claim Rejections - 35 USC § 112
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 19-21 rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The instant claims are drawn to a method for increasing AAV vector gene transfer to non-liver cells and a method for decreasing AAV liver toxicity comprising administering to a subject an inhibitor of AAVR prior to or at the same time as the administration of the AAV vector comprising CD47.
It is noted that the claimed method that administers an AAV vector comprising CD47 to cells other than the liver by blocking AAVR in the liver is merely generically disclosed in a prophetic manner, and furthermore, page 11 of the specification at best discloses that the gene therapy vector “comprises the addition of CD47 on the surface of the viral vector” “for reducing the elimination of viral vectors in vivo”. Hence, CD47 on the surface of the AAV gene therapy vector appears to have nothing to do with the claimed effects of increasing AAV gene transfer to non-liver cells and decreasing AAV liver toxicity.
Although a method of reducing AAV delivery to target cells including liver cells by inhibiting AAVR in the target cells by administering an inhibitor (e.g., RNAi agent) targeting AAVR was known in the relevant prior art as evidenced by Pillay et al. (WO 2017/083423 A1, applicant’s citation), the combination method that co-administers an inhibitor of AAVR an AAV vector comprising CD47 was not known in the prior art. As such, the instant specification must adequately describe the claimed method in sufficient detail in order to comply with the written description requirement as there is no relevant knowledge pertaining to the methods that encompass and require the instantly claimed co-administration “for increasing adeno-associated virus (AAV) vector gene transfer to cells other than the liver and/or decreasing AAV liver toxicity in a subject”. In the instant case, there is no adequate written description support, other than the disclosure that CD47 on the surface of a viral vector is useful “for reducing the elimination of viral vectors in vivo”, wherein such disclosure is not found sufficient to describe that CD47-expressing AAV gene therapy vector co-administered with an AAVR inhibitor results in the claimed, required effects in a subject.
See MPEP §2163 teaching that “there is an inverse correlation between the level of skill and knowledge in the art and the specificity of disclosure necessary to satisfy the written description requirement. Information which is well known in the art need not be described in detail in the specification. See, e.g., Hybritech, Inc. v. Monoclonal Antibodies, Inc., 802 F.2d 1367, 1379-80, 231 USPQ 81, 90 (Fed. Cir. 1986). However, sufficient information must be provided to show that the inventor had possession of the invention as claimed.” (emphasis added).
In view of the foregoing, the method of claims 19-21 is not adequately described by the instant specification in the manner to reasonably convey to one skilled in the relevant art that the instant co-inventors had possession of the claimed method as of the filing date sought in the instant application.
Claim Rejections - 35 USC § 102
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 22-24 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Pillay et al. (WO 2017/083423 A1, of record).
Pillay discloses a method of reducing AAV infection in target cells or reducing delivery of a “gene therapy” AAV particle/vector “that includes a nucleic acid of interest” to target cells in vivo in an individual comprising contacting the target cell with an agent that inhibits AAVR that binds to AAV, wherein the target cells are “liver cells” and the agent administration is followed by contacting the target cell with the AAV particle, wherein the agent is “an anti-AAVR RNAi agent (i.e., an RNAi agent such as an shRNA, an siRNA, or a microRNA that specifically targets AAVR)”, wherein “cells with decreased levels of AAVR are less permissive to AAV infection.” See pages 1, 5, 10, 23, 71-72, 75-80; claims 53-66.
Accordingly, claims 22-24 are described by Pillay et al.
Conclusion
No claim is 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 DANA H SHIN whose telephone number is (571)272-8008. The examiner can normally be reached Monday-Thursday: 8am - 6:30pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, RAM SHUKLA can be reached at 571-272-0735. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/DANA H SHIN/Primary Examiner, Art Unit 1635
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