DETAILED ACTION
This Office Action is in response to Applicant’s Amendment and Remarks filed on 09 March 2026 in which claims 2 and 3 were canceled, claims 1, 11, 15, 16 and 32 were amended to change the scope and breadth of the claims, and claims 82-84 were newly added.
Claims 1, 4-12, 15, 16, 24, 28, 29, 32, 34 and 82-84 are pending in the current application. Claims 6-10 remain withdrawn as being drawn to a non-elected species. Claims 1, 5, 11, 12, 15, 16, 24, 28, 29, 32, 34 and 82-84 are examined on the merits herein.
The Declaration of Dr. Napoleone Ferrara, submitted by Applicant on 09 March 2026 under 37 CFR §1.132 are acknowledged and will be further discussed below.
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 .
Drawings
The drawings were received on 09 March 2026. These drawings are acceptable.
Modified Rejections
The following are new ground(s) or modified rejections necessitated by Applicant's amendment, filed on 09 March 2026, where the limitations in pending claims 1, 11, 15, 16 and 32 as amended now have been changed and claims 82-84 have been newly added. Therefore, rejections from the previous Office Action, dated 11 September 2025, have been modified and are listed below.
Response to Arguments
Applicant's arguments, filed 09 March 2026, with respect to the rejection under 35 U.S.C. §102(a)(1)/(a)(2), have been fully considered but they are not persuasive.
Applicant contends Huizing does not teach administering the D-enantiomer of N-acetylmannosamine, as claimed.
The above argument is not found persuasive, because the structure of N-acetyl mannosamine shown in claim 1 of Huizing is in the configuration of the D-enantiomer.
PubChem (cited in PTO-892) disclose a flat representation of the D-mannosamine, and the stereochemistry at C2, C3, C4 and C5. The stereochemical orientation disclosed by PubChem for D-mannosamine is supported by Millipore Sigma (cited in PTO-892), which shows the Haworth standard orientation. The D-mannosamine disclosed by PubChem and Millipore Sigma have the same stereochemical orientation as the N-acetyl mannosamine derivatives disclosed by Huizing. Thus, Huizing disclose N-acetyl-D-mannosamine.
Santa Cruz Biotechnology (cited in PTO-892) catalog disclose a flat representation of L-mannosamine, and the stereochemistry at C2, C3, C4 and C5. The stereochemical orientation disclosed by Santa Cruz Biotechnology for L-mannosamine is supported by the chair form of L-mannose disclosed by Chem Impex (cited in PTO-892).
As further evidenced by SciFinder, the mannosamine of Huizing is registered as N-acetyl-D-mannosamine (cited in PTO-892).
Thus, there is evidence to support the mannosamine of Huizing et al. is the D-enantiomer.
Thus, the rejection is hereby maintained.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1, 4, 5, 11, 12, 15, 16, 28, 29, 32, 34, 83 and 84 are rejected under 35 U.S.C. 102(a)(1)/(a)(2) as being anticipated by Huizing et al. (US Patent Application Publication No. 2020/0046747, cited in previous Office Action).
Huizing et al. disclose the use of sialylation increasing therapies, such as N-acetyl-mannosamine and derivatives thereof, for the treatment of cardiovascular disorders associated with oxidative stress (para [0003]). Huizing et al. disclose a method for treating a subject with a cardiovascular disorder associated with oxidative stress, and does not have a GNE myopathy comprising administering to the subject a therapeutically effective amount of mannosamine, N-acetyl mannosamine or a derivative thereof (claim 1). The subject has a stroke (claim 2). The method includes treating thrombotic stroke (para [0099]). The sialylation increasing therapeutic can be administered as a single dose or a divided dose (i.e. multiple dosing treatment regimens), (para [0117]). The amount includes 0.1 to about 1 g (i.e. 100 mg to about 1 g), (para [0119]). It can be administered as a prophylactic or therapeutic (i.e. pretreatment or post-treatment). It can be administered locally or systemically (para [0118]). Forms include an oral tablet (para [0126]), or for parenteral administration (para [0128]). The mannosamine may be administered as a solution (para [0123]).
The recitation “wherein the administering is effective to stimulate endothelial cell proliferation and angiogenesis of blood vessels near a brain or effective to stimulate brain endothelial cell proliferation and angiogenesis” in claim 29 necessarily occurs upon performing the positively recited step. The same applies to present claims 28, 32 and 34.
Since claim 1 of Huizing et al. only includes administering mannosamine, Huizing meets the limitation of newly added claims 83 and 84.
Thus, the disclosure of Huizing et al. anticipates claims 1, 4, 5, 11, 12, 15, 16, 28, 29, 32, 34, 83 and 84 of the present application.
Response to Arguments
Applicant's arguments, filed 09 March 2026, with respect to the rejection under 35 U.S.C. §103, have been fully considered but they are not persuasive.
Applicant contends one of ordinary skill in the art would not have had a reasonable expectation of success in using D-mannosamine (ManN) to treat stroke, because Huizing pertains to using N-acetyl mannosamine to treating GNE myopathy.
The above argument is not found persuasive, because prior art is presumed to be enabled per MPEP 2121(I) and (III), “A prior art reference provides an enabling disclosure and thus anticipates a claimed invention if the reference describes the claimed invention in sufficient detail to enable a person of ordinary skill in the art to carry out the claimed invention; "proof of efficacy is not required for a prior art reference to be enabling for purposes of anticipation.".
Applicant has also provided data showing ManN and N-acetyl mannosamine have different effects in a cerebral ischemia mouse model. The experimental timeline, including drug administration…is depicted in Figure 2A.
It is respectfully noted the amount of drug administered is not disclosed. It is not known if this amount is the same or different than the amount disclosed by Huizing. It is not clear how the experiment disclosed in the Declaration differentiates the present claims from the disclosure of Huizing et al., wherein the present claims are anticipated by the disclosure of Huizing et al.
The rejection is hereby maintained.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1, 4, 5, 11, 12, 15, 16, 28, 29, 32, 34, and 82-84 are rejected under 35 U.S.C. 103 as being unpatentable over Huizing et al. (cited above) in view of Hsieh et al. (US Patent Application Publication No. 2021/0379151, cited in previous Office Action).
Huizing et al. teach as discussed above.
Huizing et al. do not expressly disclose further administering VEGF, or a derivative thereof (present claim 24). Huizing et al. do not expressly disclose the pH of the solution (present claim 82).
Hsieh et al. teach a method for delivering a therapeutic agent to the brain of a subject, the method comprising administering a VEGF polypeptide systemically to a subject in need thereof, administering to the subject systemically an effective amount of a therapeutic agent, and then administering a second dose of a VEGF polypeptide (claim 1). The subject is a human patient, having, is at risk for a brain stroke (claim 17). The term “stroke” may be referred to as ischemic stroke, and includes thrombotic stroke (para [0107]). Hsieh et al. teach VEGF derivatives create a transient window, during which the blood brain barrier (BBB) has enhanced permeability, allowing for entry of therapeutic agents into the brain (para [0006]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to administer a VEGF derivative and mannosamine to a subject to treat thrombotic stroke.
The ordinary artisan would have known VEGF derivatives can be administered to a subject suffering from, or at risk from a stroke to increase the permeability of the BBB to therapeutic active agents. mannosamine is a known active agent useful for treating a stroke, including a thrombotic stroke. Thus, one of ordinary skill in the art would have been motivated to administer VEGF to increase the permeability of mannosamine to treat or prevent a thrombotic stroke.
One having ordinary skill in the art would have been motivated to administer mannosamine in the form of a solution, because Huizing et al. expressly teach it as an optional formulation. The ordinary artisan would have been motivated to administer mannosamine in a solution at a pH of around 7, to ensure it is at an acceptable physiologically pH that is safe for oral administration.
Thus, the claimed invention as a whole is prima facie obvious over the combined teaching of the prior art.
Conclusion
In view of the rejections to the pending claims set forth above, 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.
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/BAHAR CRAIGO/
Primary Examiner
Art Unit 1699