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 6-8, 11-13, 17, 19, 20, 23, 26, 27, 30, 32-34, 36-46, 49-51, 53 have been canceled. Claim 58 has been added. Claims 1-5, 9, 10, 14-16, 18, 21, 22, 24, 25, 28, 29, 31, 35, 47, 48, 52, 54-58 are pending.
Applicant's arguments filed 1-9-25 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Claims 1-5, 9, 10, 14-16, 18, 21, 22, 24, 25, 28, 29, 31, 35 have been withdrawn.
Claims 47, 48, 52, 54-58 are under consideration.
Specification
The title will have to be changed to more clearly set forth the elected invention.
Claim Objections
Claim 48 contains “a a”.
Claim 55 can be written more simply as ---nucleic acid sequence encoding a therapeutic or prophylactic protein---.
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.
35 USC § 112
Written Description
The rejection regarding any “designer receptor exclusively activated by designer drugs (DREADD)” as required in claims 48-54 has been withdrawn because the concept has been deleted.
The rejection regarding any “agent that is to be exogenously administered” as required in claim 50 that is the “designer drug” in claim 48 has been withdrawn because claim 50 has been canceled.
The rejection regarding “hD3q” in claim 52 has been withdrawn because it has been changed to “hM3Dq”. The structure/function of “hM3Dq” was described by Bowrey (WO 2018045178) and Zhang (Nat. Neurosci., 2015, Vol. 18, No. 4, pg 553-561).
The rejection regarding a DREADD that is an “engineered M4 muscarinic acetylcholine receptor” in claim 53 has been withdrawn because the claim has been canceled.
The rejection regarding “hM4Di” in claim 54 has been withdrawn. The structure/function of “hM4Di” was described by Bowrey (WO 2018045178) and Hou (Cell, 2016, Vol. 167, No. 1, pg 73-86).
The rejection regarding an “exogenously controllable protein” in claim 55 has been withdrawn because the concept has been deleted.
The rejection regarding shRNA and miRNA being “gene products” in claim 57 has been withdrawn in view of the amendment.
The rejection regarding “intrabody” in claim 57 has been withdrawn because the concept has been deleted.
Indefiniteness
The rejection regarding the metes and bounds of a “designer receptor exclusively activated by designer drugs (DREADD)” in claim 48 has been withdrawn because the concept has been deleted.
The rejection regarding the “agent that is to be exogenously administered” is the “designer drug” in claim 50 has been withdrawn because the claim has been canceled.
The rejection of claim 51 has been withdrawn because the claim has been canceled.
The rejection regarding “hD3q” in claim 52 has been withdrawn because it has been changed to “hM3Dq”. The structure/function of “hM3Dq” was described by Bowrey (WO 2018045178) and Zhang (Nat. Neurosci., 2015, Vol. 18, No. 4, pg 553-561).
The rejection regarding the metes and bounds of a DREADD that is an “engineered M4 muscarinic acetylcholine receptor” in claim 53 has been withdrawn because the claim has been canceled.
The rejection regarding “hM4Di” in claim 54 has been withdrawn. The structure/function of “hM4Di” was described by Bowrey (WO 2018045178) and Hou (Cell, 2016, Vol. 167, No. 1, pg 73-86).
The rejection regarding the metes and bounds of the phrase “exogenously controllable protein” encompasses any protein” in claim 55 has been withdrawn in view of the amendment.
The rejection regarding the terms shRNA and miRNA in claim 57 being “gene products” as required in claim 57 has been withdrawn in view of the amendment.
The rejection regarding the metes and bounds of an “intrabody” in claim 57 has been withdrawn because the term has bee deleted.
Claim Rejections - 35 USC § 103
A) Claim 47, 55, 57 remain and claim 58 is rejected under 35 U.S.C. 103 as being unpatentable over Esteves (2019/0038773) in view of Vandenberghe (8999678) and Dudman (WO 2017/218842).
Esteves taught an AAV particle comprising AAV capsid proteins from different AAV serotypes including AAV2, AAV8, AAV9, AAVrh8, and AAVrh10 (para 48).
Esteves did not teach the AAV capsid proteins were a retroAAV2 capsid protein comprising the amino acid sequences of SEQ ID NO: 5 and an AAVrh10 capsid protein comprising the amino acid sequences of SEQ ID NO: 7 as required in claim 47.
However, Dudman taught AAV2 capsid protein mutant 5R-Hin6 (retroAAV2) identified as SEQ 44 (col. 2, line 41) of 748 amino acids in length having 100% sequence homology with the amino acid sequence of SEQ ID NO:5:
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And Vandenberghe taught an AAVrh10 capsid protein of rhesus adeno-associated virus, 10 (e.g., rh.10 capsid) identified as SEQ ID NO: 25 (col. 2, line 29) of 738 amino acids in length having 100% sequence homology with the claimed amino acid sequence of SEQ ID NO:7:
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Thus, it would have been obvious to those of ordinary skill in the art at the time of filing to make an AAV particle comprising capsid proteins from different AAV serotypes as described by Esteves using a retroAAV capsid protein comprising the amino acid sequences of SEQ ID NO: 5 described by Dudman and an AAVrh10 capsid protein comprising the amino acid sequences of SEQ ID NO: 7 described by Vandenberghe. Those of ordinary skill in the art at the time of filing would have been motivated to use the retroAAV protein of Dudman because Dudman disclosed it provided efficient retrograde access to projection neurons for the delivery of sensors and effectors (col. 2, lines 12-15). Those of ordinary skill in the art at the time of filing would have been motivated to use the AAVrh10 capsid of Vandenberghe because Vandenberghe taught the capsid improved transgene delivery.
Esteves taught the AAV encoded a transgene encoding a protein for treating a disease (para 15, 76) which is equivalent to a “therapeutic gene product” in claim 55.
Dudman taught the AAV encoded Cas9 or an antibody as required in claim 57 (claims 15, 29)
Esteves taught the AAV encoded a transgene encoding a miRNA for treating a disease (para 77, 78) as required in claim 58. Dudman taught the AAV encoded miRNA (claim 13, 31).
Response to arguments
Applicants argue their arguments were not considered (pg 17 of the response filed 10-2-25). All arguments that applied to pending rejections were addressed.
Applicants argue the examiner has failed to make a prima facie case of obviousness because the examiner did not demonstrate those of skill would have combined the references to arrive at the claimed invention (pg 18). Applicants’ argument is not persuasive. Every element claimed is discussed in the rejection. Two motivational statements have been provided to combine the references.
Applicants argue those of skill would not have combined AAVrh10 capsid with retroAAV capsid (pg 18-19). Applicants’ argument is not persuasive because it is unfounded. Those of ordinary skill in the art at the time of filing would have been motivated to use the retroAAV protein of Dudman because Dudman disclosed it provided efficient retrograde access to projection neurons for the delivery of sensors and effectors (col. 2, lines 12-15). Those of ordinary skill in the art at the time of filing would have been motivated to use the AAVrh10 capsid of Vandenberghe because Vandenberghe taught the capsid improved transgene delivery.
Applicants’ discussion of Esteves on pg 19 is noted, but applicants’ conclusion that Esteves somehow teaches away from combining AAVrh10 and retroAAV capsids is logically flawed. Esteves taught an AAV particle comprising AAV capsid proteins from different AAV serotypes including AAV2, AAV8, AAV9, AAVrh8, and AAVrh10 (para 48). Examples 3 and Fig. 6 exemplify an AAVrh10 in conjunction with K16ApoE. This is hardly a teaching away from anything. In no way does Esteves teach away from combining AAV capsid proteins from different serotypes because Esteves expressly teaches doing so.
Applicants’ discussion of Vandenberghe (pg 19-20) and Dudman (pg 20-21) are noted, but again illogically concludes Vandenberghe and Dudman teach away from combining AAVrh10 and retroAAV capsids. Perhaps applicants are attempting to say Vandenberghe and Dudman do not provide specific and literal motivation to combining AAVrh10 and retroAAV capsids; however, motivation to combine need not be expressly recited in Vandenberghe or Dudman. Two motivational statements have been provided which may not be the same motivation as the inventors. Obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007).
Applicants’ discussion of Bowrey and Greenberg are noted (pg 21) but are misplaced because they are not part of this rejection. Applicants’ arguments for each rejection should be made separate. While portions may be repeated or references, arguing the obviousness rejections together is inapt and confusing.
Applicants argue the examiner has made no actual rationale or motivation for why those of skill would combine AAVrh10 and retroAAV capsids. Applicants’ argument is false and not persuasive. Two motivational statements are in the rejection.
Applicants repeat the discussion of Vandenberghe on pg 22 which is not persuasive for reasons set forth above.
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).
The combined teachings of Esteves, Vandenberghe, and Dudman taught an AAV comprising a retroAAV2 capsid protein comprising the amino acid sequences of SEQ ID NO: 5 and an AAVrh10 capsid protein comprising the amino acid sequences of SEQ ID NO: 7 and a nucleic acid sequence encoding a therapeutic protein for reasons set forth above.
The combined teachings of Esteves, Vandenberghe, and Dudman did not teach the therapeutic protein was hM3Dq as required in claim 52 or hM4Di in claim 54 (both of which are apparently encompassed by claim 48).
However, Bowrey taught making AAV encoding hM3Dq or hM4Di for treating disease (Table 2; pg 28-29) which are described by applicants as being part of the invention (claims 52 and 54).
Thus, it would have been obvious to those of ordinary skill in the art at the time of filing to make an AAV comprising capsids comprising the amino acids of SEQ ID NO: 5 and 7 and a nucleic acid sequence encoding a protein as described by the combined teachings of Esteves, Vandenberghe, and Dudman wherein the protein was hM3Dq or hM4Di described by Bowrey. Those of ordinary skill in the art at the time of filing would have been motivated to replace the protein of Esteves with the protein of Bowrey for research into the role of expression of hM3Dq or hM4Di in disease either in vitro or in vivo.
Response to arguments
Applicants mention Bowrey on pg 21 but appear to believe the rejection using the combined teachings of Esteves, Vandenberghe, and Dudman is flawed. Applicants’ argument is 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).
The combined teachings of Esteves, Vandenberghe, and Dudman taught an AAV comprising a retroAAV2 capsid protein comprising the amino acid sequences of SEQ ID NO: 5 and an AAVrh10 capsid protein comprising the amino acid sequences of SEQ ID NO: 7 and a nucleic acid sequence encoding a therapeutic protein for reasons set forth above.
The combined teachings of Esteves, Vandenberghe, and Dudman did not teach the therapeutic protein was a nicotinic acetylcholine receptor (nAChR) as required in claim 56.
However, Greenberg taught making AAV encoding nAChR for treating disease (pg 44, para 258-274).
Thus, it would have been obvious to those of ordinary skill in the art at the time of filing to make an AAV comprising capsids comprising the amino acids of SEQ ID NO: 5 and 7 and a nucleic acid sequence encoding a protein as described by the combined teachings of Esteves, Vandenberghe, and Dudman wherein the protein was nAChR described by Greenberg. Those of ordinary skill in the art at the time of filing would have been motivated to replace the protein of Esteves with the protein of Greenberg for research into the role of expression of nAChR in disease either in vitro or in vivo. Doing so was well-known as shown by Greenberg in Example 2, so those of skill would have had a reasonable expectation of replacing the coding sequences and making the virus using the teachings of Esteves, Vandenberghe, Dudman, and Greenberg.
Response to arguments
Applicants mention Greenberg on pg 21 but appear to believe the rejection using the combined teachings of Esteves, Vandenberghe, and Dudman is flawed. Applicants’ argument is not persuasive for reasons set forth above.
D) Claims 47, 48, 52, 54, 55, 57 remain and claim 58 is 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).
Bowrey taught making AAV encoding hM3Dq or hM4Di for treating disease (Table 2; pg 28-29).
Bowrey did not teach the AAV had a retroAAV2 capsid protein comprising the amino acid sequences of SEQ ID NO: 5 and an AAVrh10 capsid protein comprising the amino acid sequences of SEQ ID NO: 7 as required in claim 47.
However, Esteves taught an AAV particle comprising AAV capsid proteins from different AAV serotypes including AAV2, AAV8, AAV9, AAVrh8, and AAVrh10 (para 48);
Dudman taught AAV2 capsid protein mutant 5R-Hin6 (retroAAV2) identified as SEQ 44 (col. 2, line 41) of 748 amino acids in length having 100% sequence homology with the amino acid sequence of SEQ ID NO: 5 (see alignment above); and
Vandenberghe taught an AAVrh10 capsid protein of rhesus adeno-associated virus, 10 (e.g., rh.10 capsid) identified as SEQ ID NO: 25 (col. 2, line 29) of 738 amino acids in length having 100% sequence homology with the claimed amino acid sequence of SEQ ID NO: 7 (see alignment above).
Thus, it would have been obvious to those of ordinary skill in the art at the time of filing to make an AAV particle encoding hM3Dq or hM4Di described by Bowrey using a retroAAV capsid protein comprising the amino acid sequences of SEQ ID NO: 5 described by Dudman and an AAVrh10 capsid protein comprising the amino acid sequences of SEQ ID NO: 7 described by Vandenberghe. Those of ordinary skill in the art at the time of filing would have been motivated to use the retroAAV protein of Dudman because Dudman disclosed it provided efficient retrograde access to projection neurons for the delivery of sensors and effectors (col. 2, lines 12-15). Those of ordinary skill in the art at the time of filing would have been motivated to use the AAVrh10 capsid of Vandenberghe because Vandenberghe taught the capsid improved transgene delivery. Those of ordinary skill in the art at the time of filing would have been motivated to two different capsid proteins being combining made them more efficient at transfection as described by Esteves. Those of skill would have had a reasonable expectation of successfully manipulating the AAV capsid proteins of Bowrey as evidenced by Esteves who used mixed species of capsid proteins in one AAV and Vandenberghe and Dudman who manipulated AAV vectors to express SEQ ID NO: 5 and 7.
hM3Dq and hM4Dq described by Bowrey are therapeutic or prophylactic as required in claim 55.
Dudman taught the AAV encoded Cas9 or an antibody as required in claim 57 (claims 15, 29)
Esteves taught the AAV encoded a transgene encoding a miRNA for treating a disease (para 77, 78) as required in claim 58. Dudman taught the AAV encoded miRNA (claim 13, 31).
Response to arguments
Applicants do not appear to specifically 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).
Greenberg taught making AAV encoding nAChR for treating disease (pg 44, para 258-274).
Greenberg did not teach the AAV had a retroAAV2 capsid protein comprising the amino acid sequences of SEQ ID NO: 5 and an AAVrh10 capsid protein comprising the amino acid sequences of SEQ ID NO: 7 as required in claim 47.
However, Esteves taught an AAV particle comprising AAV capsid proteins from different AAV serotypes including AAV2, AAV8, AAV9, AAVrh8, and AAVrh10 (para 48);
Dudman taught AAV2 capsid protein mutant 5R-Hin6 (retroAAV2) identified as SEQ 44 (col. 2, line 41) of 748 amino acids in length having 100% sequence homology with the amino acid sequence of SEQ ID NO: 5 (see alignment above); and
Vandenberghe taught an AAVrh10 capsid protein of rhesus adeno-associated virus, 10 (e.g., rh.10 capsid) identified as SEQ ID NO: 25 (col. 2, line 29) of 738 amino acids in length having 100% sequence homology with the claimed amino acid sequence of SEQ ID NO: 7 (see alignment above).
Thus, it would have been obvious to those of ordinary skill in the art at the time of filing to make an AAV particle encoding nAChR described by Greenberg using a retroAAV capsid protein comprising the amino acid sequences of SEQ ID NO: 5 described by Dudman and an AAVrh10 capsid protein comprising the amino acid sequences of SEQ ID NO: 7 described by Vandenberghe. Those of ordinary skill in the art at the time of filing would have been motivated to use the retroAAV protein of Dudman because Dudman disclosed it provided efficient retrograde access to projection neurons for the delivery of sensors and effectors (col. 2, lines 12-15). Those of ordinary skill in the art at the time of filing would have been motivated to use the AAVrh10 capsid of Vandenberghe because Vandenberghe taught the capsid improved transgene delivery. Those of ordinary skill in the art at the time of filing would have been motivated to two different capsid proteins being combining made them more efficient at transfection as described by Esteves. Those of skill would have had a reasonable expectation of successfully manipulating the AAV capsid proteins of Greenberg as evidenced by Esteves who used mixed species of capsid proteins in one AAV and Vandenberghe and Dudman who manipulated AAV vectors to express SEQ ID NO: 5 and 7.
nAChR described by Greenberg is therapeutic or prophylactic as required in claim 55.
Greenberg described using nAChR as required in claim 56.
Response to arguments
Applicants do not appear to specifically address this rejection.
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.
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