DETAILED ACTION
Applicant’s amendment to the claims in the Response filed on 03/27/2026, materially changing the scope of the claims, is acknowledged.
The rejection of record under 35 U.S.C. § 102 is withdrawn in view of Applicant’s amendment to the claims in the Response filed on 03/27/2026.
The rejections of record under 35 U.S.C. § 103 are maintained and modified in view of Applicant’s amendment to the claims in the Response filed on 03/27/2026, materially changing the scope of the claims, as set forth below.
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.
Claims 1-6, 9, and 14-18 are rejected under 35 U.S.C. 103 as being unpatentable over Tsai et al. (ARVO Annual Meeting Abstract (2018), prior art of record, hereinafter “Tsai”) in view of Tsai et al. (Exp. Eye Res., 87:242-250 (2008), hereinafter “Tsai2”), Tang et al. (JoVE, 50:1-3 (2011), hereinafter “Tang”) and Nakazawa et al. (Japan. J. Ophthal., 64:243-249 (2020), hereinafter “Nakazawa”).
Tsai teaches a method for treating optic neuropathy in a rat (rodent/mammal) model of anterior ischemic optic neuropathy (rAION) comprising administering to the rat a pharmaceutical composition comprising an effective amount of NEULASTA, i.e., PEGylated G-CSF (PEG-GCSF) and a pharmaceutically acceptable excipient thereof, which reads of a non-immunogenic hydrophilic polymer covalently linked to G-CSF, via a single intravitreal injection, before 2 days post-infract (e.g., day 0 and 1 post-rAION induction, i.e., within one month after the optic neuropathy occurs) (pages 1-2).
Tsai does not teach that the optic neuropathy is a type recited by claim 1, as amended, such as traumatic optic neuropathy or glaucomatous optic neuropathy. However, Tsai2 teaches that G-CSF also exerts neuroprotective effects after optic nerve crush (ONC) in rats (Abstract). Tang teaches that ONC is an important experimental disease model for traumatic optic neuropathy, glaucoma, etc. (Abstract). Nakazawa teaches that glaucomatous optic neuropathy is the pathohistological feature of glaucoma in the optic nerve (Abstract).
Taken together, the prior art broadly recognized the utility of G-CSF for the treatment of various optic neuropathies, including anterior ischemic optic neuropathy, traumatic optic neuropathy, and glaucomatous optic neuropathy. As such, it would have been prima facie obvious at the time of filing to extend the long-acting treatment regime taught by Tsai to other optic neuropathies in order to advantageously treat the neuropathies with a long-acting G-CSF formulation, which Tsai further teaches advantageously has much longer half-life thereby reducing the necessity of consecutive daily injections (pages 1-2). One of ordinary skill in the art would have had a reasonable expectation of success because, as discussed above, the prior art recognized that G-CSF exerts a neuroprotective effect in various optic neuropathy models, including rAION and ONC corresponding to diverse optic neuropathies, including anterior ischemic optic neuropathy, traumatic optic neuropathy, and glaucomatous optic neuropathy.
Regarding claim 9, it would have been a matter of routine experimentation using standard laboratory techniques available at the time of filing to determine the optimal concentration of the PEG-GCSF for use in the method taught by Tsai, Tsai2, Tang, and Nakazawa to maximize the therapeutic effect while minimizing complications, side effects, etc. with a reasonable expectation of success. Generally, differences in concentration will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
Accordingly, the claimed invention was prima facie obvious to one of ordinary skill in the art at the time of filing especially in the absence of evidence to the contrary.
Claims 7-8 are rejected under 35 U.S.C. 103 as being unpatentable over Tsai, Tsai2, Tang, and Nakazawa as applied to claims 1-6, 9, and 14-18 above, and further in view of Cox et al. (Exp. Hematol., 32:441-449 (2004), prior art of record, hereinafter “Cox”).
As discussed above, claims 1-6, 9, and 14-18 were rendered prima facie obvious by Tsai, Tsai2, Tang, and Nakazawa. As further discussed above, Tsai discloses a long-acting G-CSF, i.e., PEG-GCSF, with a longer half-life than G-CSF. The references do not explicitly teach that the G-CSF is fused to an Fc fragment of IgG. However, Cox teaches a G-CSF fused to the Fc domain of IgG1 (Title, Abstract). Cox further teaches that this fusion enhances the half-life of G-CSF (Abstract). One of ordinary skill in the art would have been free to substitute the long-acting PEG-GCSF taught by Tsai for the long-acting IgG1-Fc-GCSF taught by Cox with a reasonable expectation of success because, inter alia, the prior art evidences that both PEG-GCSF and IgG1-Fc-GCSF are long-acting G-CSFs with longer half-lives than GCSF alone and, therefore, would be a simple substitution of one known element for another to obtain predictable results.
Accordingly, the claimed invention was prima facie obvious to one of ordinary skill in the art at the time of filing especially in the absence of evidence to the contrary.
Response to Arguments
Applicant's arguments and Rule 132 Declaration (the “Declaration”), filed 03/27/2026, have been fully considered but they are not persuasive. Applicant’s arguments and Declaration are discussed to the extent they apply to the current grounds of rejection set forth above.
On page 6 of the Response and in the Declaration, Applicant urges that AION/NAION has a distinct pathogenesis compared to the optic neuropathies recited in claim 1, as amended, and, therefore, a person of ordinary skill in the art would not reasonably expect that therapeutic effects observed in AION/NAION could be extrapolated to these other optic neuropathies.
As discussed above, Tsai teaches treating optic neuropathy in an AION/NAION model using G-CSF. As further discussed above, Tsai2 teaches treating optic neuropathy in an ONC model using G-CSF, which is an important experimental disease model for traumatic optic neuropathy, glaucoma (glaucomatous optic neuropathy), etc. See also Huang et al. (Exp. Eye. Res., 143:132-140 (2016)), systemic and intravitreal application of G-CSF show significantly neuroprotective effects on RGCs after ON crush injury (page 139).
The prior art broadly recognized the neuroprotective effects of G-CSF in various optic neuropathy models (AION/NAION and ONC) corresponding to distinct optic neuropathies such as ischemic optic neuropathy, traumatic optic neuropathy, and glaucomatous optic neuropathy. As such, the prior art of record evidences that a person of ordinary skill in the art would have reasonably expected that the therapeutic effects observed in the AION/NAION model used by Tsai would extrapolate to other optic neuropathies.
On pages 6-7 of the Response, Applicant urges the claimed method achieves various unexpected results. The results in the Specification do not appear unexpected results given, inter alia, that the data is limited to only PEG-GCSF, which was already in known and in use at the time of filing, and the data does not compare PEG-GCSF to any other GCSF formulation. As such, the data appears consistent with the use of GCSF/PEG-GCSF taught by the prior art of record for the treatment of optic neuropathies.
Applicant’s remaining arguments were fully considered, but were not found persuasive for the reasons set forth above.
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 THOMAS J VISONE whose telephone number is (571)270-0684. The examiner can normally be reached Monday-Thursday, 8:30 AM to 6:30 PM.
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/THOMAS J. VISONE/ Supervisory Patent Examiner, Art Unit 1672
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