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 .
Claims 1-46, 49-51, 53 have been canceled. Claims 47, 48, 52, 54-58 are pending.
Applicant's arguments filed 6-29-26 have been fully considered but they are not persuasive.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Election/Restrictions
Applicants elected Group III, claims 37, 46-57, with traverse in the reply filed on 5-28-24. The requirement was deemed proper, remains proper, and is made FINAL.
Claims 47, 48, 52, 54-58 are under consideration.
Specification
The title has been changed to more clearly set forth the elected invention.
Claim Interpretation
It is assumed the phrases “light-sensitive ion channel”, “chemically-responsive ion channel”, “ultrasound-sensitive ion channel”, and “magnetic field-responsive ion channel” in claim 48 were well-known and definite.
The structures/functions of hM3Dq in claim 52 and hM4Di in claim 54 were well-known as described by Bowrey (WO 2018045178), Zhang (Nat. Neurosci., 2015, Vol. 18, No. 4, pg 553-561), and Hou (Cell, 2016, Vol. 167, No. 1, pg 73-86).
It is assumed the channel rhodopsin, nicotinic acetylcholine receptor, gramicidin A, voltage-gated potassium channel, ionotropic glutamate receptor, and α-hemolysin in claim 56 were well-known and definite.
It is assumed the term “CrispR/Cas9” in claim 57 encompasses any CRISPR or Cas9 protein.
It is assumed the term “single-chain antibody” in claim 57 was well-known and definite.
Claim Rejections - 35 USC § 103
A) Claim 47, 55, 57, 58 remain rejected under 35 U.S.C. 103 as being unpatentable over Esteves (2019/0038773) in view of Vandenberghe (8999678) and Dudman (WO 2017/218842) for reasons of record.
Response to arguments
Applicants argue the Examiner mischaracterizes Esteves and Vandenberghe (pg 7). Applicants argue Esteves did not suggest combining AAVrh10 with any specific capsid, especially retroAAV (pg 8). Applicants argue the examiner mischaracterized Esteves because Esteves did not teach combining two different capsids to make “them more efficient at transfection” (pg 8-9). Applicants point to paragraphs 26-28 of the Declaration by Georgiadis filed 6-29-26. Applicants’ argument and the Declaration are not persuasive. This rejection does not say two different capsids to make “them more efficient at transfection”. More importantly, paragraph 48 of Esteves taught using two different capsid proteins using the methods described in PCT/2015/053804 (incorporated by reference, now WO 2016/054557) which is applicants’ own work and is replete with practical means for combining capsid proteins to improve tropism to a desired tissue or modify stability (pg 17, lines 21-25; pg 17, line 32-pg 18, line 3). Para 49 of Esteves cites Choi et al., Curr Gene Ther. 2005 June; 5(3): 299-310 who taught multiplex AAVs for improved gene delivery. The arguments and declaration fail to acknowledge that Esteves taught combining two capsid proteins – it was well-known and well-established. WO 2016/054557 and Choi handily show the motivation and ability to combine specific capsids to improve tropism and modify stability. This is beyond a “general concept” as argued by applicants; it was well-known and well-established.
Applicants argue the Examiner mischaracterized Vandenberghe because Vandenberghe did not teach AAVrh10 capsid “improved transgene delivery” (pg 10). Applicants point to paragraph 24 of the Declaration. Applicants’ argument and the Declaration are not persuasive because they ignore the fact that claim 1 of Vandenberghe is a method of improving viral packaging yield, transduction efficiency, and/or gene transfer efficiency and encompasses any of the capsids contemplated. AAVrh10 is most definitely encompassed by claim 1 of Vandenberghe and is expressly shown in Fig. 4 and 5. Applicants’ conclusion that a POSITA would somehow be discouraged from using an unmodified capsid protein is legally flawed because claim 1 of Vandenberghe encompasses any capsid that is at least 85% identical to the full length aligned vp1 sequences.
Applicants argue motivation to use a particular capsid is different than motivation to combine and point to paragraphs 21, 22, and 25 of the Declaration. The Declaration says a POSITA would use retroAAV alone to achieve retrograde access to projection neurons. Applicants say “Because the addition of a second capsid protein complicates vector production, a POSITA must have a reason to add a second capsid”. Applicants’ argument is not persuasive. Applicants’ assertion that “the addition of a second capsid protein complicates vector production” is inadequate because Esteves taught doing so and cites references that taught how to achieve the goal. Even if the method were “complicated”, a POSITA could handily achieve the goal of combining AAV capsids.
Applicants argue the motivation and reasonable expectation of success statements by the Examiner are scientifically invalid and fail (pg 12-19). Applicants point to paragraphs 12-19, 23, 24, 32, 35-39 of the declaration. Applicants point to Rabinowitz (2014) and Schmit (2020). Applicants’ arguments and the declaration are not persuasive. The claims encompass obtaining any amount of success of achieving a chimeric AAV with any amount of packaging yield, transduction efficiency, or gene transfer efficiency – they do not require the AAVs with improved properties. While the declaration says the properties of AAVs with chimeric capsids cannot be predicted, WO 2016/054557, and Choi say otherwise because they provide motivation and show the ability to combine capsids to improve tropism and modify stability. It was well-known and well-within the ability of a POSITA to combine two AAV capsid proteins, and obtaining a chimeric AAV with any property as broadly encompassed by the claims. Rabinowitz taught some combinations of capsid proteins exhibited synergistic properties within the realm of transduction efficiency; however, the claims encompass AAVs with any transduction efficiency. Schmit (2020) cannot be relied upon for what was known because it was not available at the time of filing (2018).
Pg 12-19 contains duplicative arguments which have been addressed above.
Pg 17 says the claimed chimeric AV vector allows for improved uptake of AAV vectors by neuronal cell bodies (last paragraph). Applicants’ argument is not persuasive. The claims make no such requirement.
Section 3 of the arguments (pg 19-20) say the combination has unexpected property of increased “retrograde uptake” to neurons of the “nodose glanglions” after injection into the stomach wall. Applicants point to paragraphs 35-38 of the Declaration. Applicants’ arguments and the Declaration are not persuasive. The meaning of “retrograde uptake” to neurons of the nodose glanglions cannot be determined and was not taught in the original disclosure. The argument and the Declaration do not first establish what was expected from the teachings of Esteves (or Vandenberghe or Dudman) within the realm of “retrograde uptake”. The argument and the Declaration do not take secondary considerations into account for what was known about AAVrh10 and retroAAV. The argument and the Declaration do not compare what was expected to applicants’ results. Paragraphs 36 and 37 point to Fig. 1 and 2 which do not relate to the AAV of Esteves (or Vandenberghe or Dudman). Furthermore, Fig. 1 and 2A look the same for every condition. Fig. 2B is interesting, but the arguments and Declaration do not teach how it relates to what was expected from the teachings of Esteves (or Vandenberghe or Dudman).
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B) Claims 48, 52, 54 remain rejected under 35 U.S.C. 103 as being unpatentable over Esteves (2019/0038773) in view of Vandenberghe (8999678) and Dudman (WO 2017/218842) as applied to claims 47, 55, 57, 58 and further in view of Bowrey (WO 2018045178) for reasons of record.
Response to arguments
Applicants arguments are the same as those above and are not persuasive for reasons set forth above.
C) Claim 56 remains rejected under 35 U.S.C. 103 as being unpatentable over Esteves (2019/0038773) in view of Vandenberghe (8999678) and Dudman (WO 2017/218842) as applied to claims 47, 55, 57, 58 and further in view of Greenberg (20190161529) for reasons of record.
Response to arguments
Applicants arguments are the same as those above and are not persuasive for reasons set forth above.
D) Claims 47, 48, 52, 54, 55, 57, 58 remain rejected under 35 U.S.C. 103 as being unpatentable over Bowrey (WO 2018045178) in view of Esteves (2019/0038773) in view of Vandenberghe (8999678) and Dudman (WO 2017/218842) for reasons of record.
Response to arguments
Applicants arguments do not address this rejection.
E) Claims 47, 48, 55, 56 remain rejected under 35 U.S.C. 103 as being unpatentable over Greenberg (20190161529) in view of Esteves (2019/0038773) in view of Vandenberghe (8999678) and Dudman (WO 2017/218842) for reasons of record.
Response to arguments
Applicants arguments do not address this rejection.
Conclusion
No claim is allowed.
Inquiry concerning this communication or earlier communications from the examiner should be directed to Michael C. Wilson who can normally be reached at the office on Monday through Friday from 9:30 am to 6:00 pm at 571-272-0738.
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Michael C. Wilson
/MICHAEL C WILSON/
Primary Examiner, Art Unit 1638
Prosecution Insights