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 .
Applicant’s arguments and amendments filed on 1/2/2026 have been entered.
Claim 1 has been amended.
Claim 6 has been cancelled.
In view of Applicant’s amendments to claim 1, the 102(a)(1) rejection is withdrawn and the 103 rejections of record has been amended to address the incorporation of the limitations of claim 6 into claim 1.
Claims 1-3, 5 and 7-9 are examined in the instant application.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
Claim(s) 1, 2, 8 and 9s is/are rejected under 35 U.S.C. 103 as being unpatentable over Behar-Cohen et al. (US 2014/0309613 A1) in view of Lee et al. (2018, The Ocular Surface, Vol. 16, pgs. 206-217).
Regarding claim 1, Behar-Cohen et al. teach an engineered vector comprising a retina-specific promoter operably linked to a nucleic acid sequence encoding a TGF-β polypeptide (parags. 4, 6, 20 and 28).
Regarding a regulatory element, Behar-Cohen teach that their engineered vector can comprise a variety of regulatory elements (parag. 20).
Regarding claim 2, Behar-Cohen teaches that the vector can be an AAV (parags. 3 and 111).
Regarding claims 8 and 9, Behar-Cohen teaches that their engineered vector can be formulated in a pharmaceutical composition for treatment of an ocular disease (parags. 1, 8 and 35).
Behar-Cohen does not teach:
TGF-β1 polypeptide.
(i) Regarding using the TGF-β1 polypeptide, Lee et al. teach that TGF-β1 is a cytokine that is thought to have anti-inflammatory activity on the ocular surface (pg. 210 col. 3).
Thus at the time of filing the ordinary artisan would have found it prima facie obvious to substitute TGF-β1 taught by Lee for the TGF-β in the the engineered vector of Behar-Cohen to arrive at the claimed invention.
One of ordinary skill in the art would have been motivated to make such a combination since Lee teaches that TGF-β1 functions as a cytokine that may have an anti-inflammatory response in the eye (ocular surface).
There would have been a reasonable expectation of success that that the TGF-β1 of Lee could be substituted for the TGF-β of Behar-Cohen, since TGF-β1 is one of the three isoforms of TGF-β.
Thus the cited art provides the requisite teachings and motivations to make and use the invention as claimed.
Response to Arguments
Applicant’s Arguments
Applicants argue in amendment that one of ordinary skill would understand that different isoforms of the same protein can have drastically different effects, even opposite effects - see, for example, Exhibit A (Sundvall et al. 2010) which teaches two isoforms of ErbB4 stimulate either proliferation or apoptosis. In fact, in the present application, the data show that not all TGF ß isoforms had the same effect on cone survival. Figures 2D and 2E of the present application demonstrates that overexpressing TGF-B1 and TGF-B3 promoted cone preservation and survival in the central retina in mice experiencing secondary cone degeneration. However, figures 2D and 2E also demonstrate that TGF-ß2 had no effect on cone preservation and survival.
Applicant further submits that the Lee et al. reference's mention of TGF-B1 as "a cytokine that is thought to have anti-inflammatory activity on the ocular surface" (emphasis added) says nothing in regard to likelihood that expression of TGF-B1 in the retina will have benefits in promotion of survival of retinal cells. The claimed vectors drive expression of TGF- ß1 or TGF-B3 in the retina due to the operable linkage to a retina-specific promoter. The retina is a completely different tissue than the ocular surface, and the Lee et al. reference provides no guidance or suggestion to express TGF-B1 in the retina or any benefit in doing so. As such, there is no motivation to combine the teachings of Lee et al. with those of Behar-Cohen, nor is there a reasonable expectation of success if such combination is made.
Examiner’s Response
While Applicant’s arguments and evidence have been fully considered they are not found persuasive. It should be emphasized the claimed invention is a product requiring no functional limitations, only a vector and its associated components, promoter, nucleic acid, AAV etc. While claim 8 recites an intended use, for the treatment of an ocular disease, there are no functional limitations that would impart that the claimed vector can be used only for the treatment of an ocular disease or is required to be used for said treatment.
In this regard, the ordinary artisan is taught by Lee that TGF-β1 is a cytokine that is thought to have anti-inflammatory activity on the ocular surface and combined with the teachings of Behar-Cohen regarding an engineered vector comprising a retina-specific promoter operably linked to a nucleic acid sequence encoding a TGF-β polypeptide, the ordinary artisan is provided with ample motivation to substitute a nucleic acid encoding TGF-β1 for the TGF-β of Behar-Cohen. That different isoforms may behave/function differently as discussed in Exhibit A is not persuasive as there are not requirements regarding any function of the recited TGF-β1.
Thus for the reasons above and of record the rejection is maintained.
Claim(s) 3 and 5 is/are rejected under 35 U.S.C. 103 as being unpatentable over Behar-Cohen et al. (US 2014/0309613 A1) in view of Lee et al. (2018, The Ocular Surface, Vol. 16, pgs. 206-217) as applied to claims 1, 2, 8 and 9 above, and further in view of Patricio et al. (2017, Molecular Therapy: Nucleic Acids, Vol. 6, pgs. 198-208).
Behar-Cohen and Lee are relied upon above in teaching an engineered vector comprising a retina-specific promoter operably linked to a nucleic acid sequence encoding TGF-β1.
Behar-Cohen and Lee do not teach:
AAV2 and WPRE.
Regarding AAV2 AND WPRE in claims 3 and 5, Patricio et al. teach that the addition of a WPRE in an AAV2 vector enhances transduction of mouse retina (see Abstract). Specifically, Patricio teaches “Altogether, our data show that the inclusion of a WPRE sequence within an AAV2 expression cassette significantly enhances expression of target protein in the retina.” (pg. 205, col. 1 parag. 4 lines 1-3).
Thus at the time of filing the ordinary artisan would have found it prima facie obvious to modify the engineered vector of Behar-Cohen to comprise the AAV2 and WPRE of Patricio to arrive at the claimed invention.
One of ordinary skill in the art would have been motivated to make such a combination since Patrcio teaches that the combination of AAV2 and WPRE significantly enhances expression of a target protein in the retina.
There would have been a reasonable expectation of success that that the AAV2 AND WPRE would work in the engineered vector of Behar-Cohen since Patricio teaches success expression of a target protein in the retina using AAV2 and WPRE.
Thus the cited art provides the requisite teachings and motivations to make and use the invention as claimed.
Claim(s) 7 is/are rejected under 35 U.S.C. 103 as being unpatentable over Behar-Cohen et al. (US 2014/0309613 A1) in view of Lee et al. (2018, The Ocular Surface, Vol. 16, pgs. 206-217) as applied to claims 1, 2, 8 and 9 above, and further in view of Li et al. (2008, Vision Res., Vol. 48, pgs. 332-338).
Behar-Cohen and Lee are relied upon above in teaching an engineered vector comprising a retina-specific promoter operably linked to a nucleic acid sequence encoding TGF-β1.
Behar-Cohen and Lee do not teach:
Red opsin promoter
(i) Regarding using the red opsin promoter, Li et al. teach that the red opsin promoter can promote cone-specific expression in the eye when used in an AAV vector (see Abstract). Li continues to teach “we have shown that cone photoreceptor cells can be specifically targeted at high efficiency by using a human promoter of the red/green pigment genes mediated by rAAV and delivered via subretinal injections. This has significant implications for the therapy of retinal degenerations that primarily affect cone photoreceptors.” (pg. 337 col. 2 parag. 1 lines 1-6).
Thus at the time of filing the ordinary artisan would have found it prima facie obvious to modify the engineered vector of Behar-Cohen to comprise the red opsin promoter of Li to arrive at the claimed invention.
One of ordinary skill in the art would have been motivated to make such a modification since Li teaches that the red opsin promoter leads to high targeting efficiency when used in an engineered AAV (rAAV).
There would have been a reasonable expectation of success that that the red opsin promoter could be used in the engineered AAV of Behar-Cohen since Li teaches successful use of the red-opsin promoter in an engineered AAV.
Thus the cited art provides the requisite teachings and motivations to make and use the invention as claimed.
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. 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 DAVID A MONTANARI whose telephone number is (571)272-3108. The examiner can normally be reached M-Tr 8-6.
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DAVID A. MONTANARI
Examiner
Art Unit 1632
/ANOOP K SINGH/Primary Examiner, Art Unit 1632
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