DETAILED ACTION
This Office Action is in response to Applicant’s Amendment and Remarks filed on 04 May 2026 in which claims 2, 17, 18, and 26-39 were canceled, claim 1 was amended to change the scope and breadth of the claims, and claims 40 and 41 were newly added.
Claims 1, 3-16, 19-25, 40 and 41 are pending in the current application. Claims 3 and 7-16 remain withdrawn. Claims 1, 4, 6, 19-25, 40 and 41 are examined on the merits herein.
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 .
Response to Arguments
Applicant's Declaration, filed 04 May 2026, to disqualify Sloan et al. have been fully considered and is persuasive.
Applicant contends the Sloan reference (published March 18, 2020) is disqualified as prior art under 35 U.S.C. §102(b)(1)(A), because Sloan was published within a year of the priority date of the present application (October 16, 2020).
Applicant has provided an unequivocal statement from the inventor or joint inventor that the subject matter “all disclosures in Sloan et al. that are related to the subject matter claimed in above-referenced patent application, are our work or were performed under our direction” (see paragraph 2 of the Declaration submitted 04 May 2026).
Applicant has provided a reasonable explanation of the presence of additional authors listed on the Sloan reference (see paragraph 3 of the Declaration submitted 04 May 2026).
The statement made in the Response filed 04 May 2026 is sufficient to disqualify the Sloan reference.
Applicant’s arguments with respect to the rejection based on Carrillo-Carrasco and Chang, have been fully considered, but are not found persuasive.
Applicant contends Carrillo-Carrasco is drawn towards administering hydroxy cobalamin, which is chemically and therapeutically distinct from methyl cobalamin. Applicant argues they are not mere alternatives, because MeCbl is less stable and prone to degradation in UV light compared to OHCbl. Applicant argues Chang merely discloses MeCbl as a vitamin.
Applicant further argues the Specification provides evidence of unexpected super results achieved using the presently claimed methods. According to Example 4, MeCbl treatment resulted in a “striking improvement in early survival-100% of [Mmachc] mutants were alive at 100 days vs 50% of the prenatally OHCbl treated mutants”. Applicant argues, MeCbl treatment “reduced cystathionine to control levels in OHCbl treated mice, showing that MeCbl is superior to OHCbl in controlling the homocysteine remethylation to methionine in vivo”. Applicant argues one of ordinary skill in the art would not have expected such a dramatic improvement in both viability and metabolic regulation in subjects with cblC deficiency treated with MeCbl” (see page 8 of the Remarks filed 04 May 2026).
The above arguments have been fully considered, but are not found persuasive, because the results do not appear to be commensurate in scope with the claimed patient population, or recited treatment. The results in the Specification are directed towards a prenatal treatment protocol (see withdrawn claim 12), while the present and elected claims are directed towards treating a child. Additionally, the elected patient population suffers from retinal degeneration.
There is nothing in the data pointed to by Applicant that would show one of ordinary skill in the art could extrapolate the prenatal results towards children. See MPEP 716.02(d), “Whether the unexpected results are the result of unexpectedly improved results or a property not taught by the prior art, the "objective evidence of nonobviousness must be commensurate in scope with the claims which the evidence is offered to support."
The rejection is hereby maintained.
Modified Rejections
The following are new ground(s) or modified rejections necessitated by Applicant's amendment, filed on 04 May 2026, where the limitations in pending claim 1 as amended now have been changed and claims 40 and 41 have been newly added. Therefore, rejections from the previous Office Action, dated 14 January 2026, have been modified and are listed below.
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, 6, 19-25, 40 and 41 are rejected under 35 U.S.C. 103 as being unpatentable over Carrillo-Carrasco et al. (J. Inherit. Metab. Dis., 2009, vol. 32, pp. 728-731, cited in previous Office Action) in view of Chang et al. (US Patent Application Publication No. 2015/0238527, cited in previous Office Action), and further in view of Ogden et al. (Advance Data, number 347, 2004, 18 pages, cited in PTO-892).
Carrillo-Carrasco et al. teach treating a 13-year-old (a child) with elevated levels of methylmalonic acid (MMA) and total homocysteine (tHcy) (p.729, Case Report and methods). At 13 years of age, the patient had pigmentary retinopathy with severely constricted visual fields. Metabolic measurements obtained after an overnight fast showed tHCy 112 µmol/L, plasma MMA 25 µmol/L, propionyl carnitine 3.92 µmol/L, methionine 17 µmol/L and a plasma vitamin B12 level of 58-680 pg/mL. To determine the dose of OHCbl required for an optimal response, step-wise dose escalation was performed at 1-month intervals using the following dosing regimen: 10 mg IM three times weekly, 10 mg IM daily and 20 mg IM daily. OHCbl was formulated at either 10 mg/mL or 20 mg/mL. The regimen also included betaine 8 g (140 mg/kg), carnitine 500 mg (9mg/kg), folic acid 1 mg daily and modest whole-protein restriction (1.2 g/kg per day). Carrillo-Carrasco et al. observed a dose-dependent response with an 80% reduction of plasma MMA, a 55% reduction of tHCy and a greater than twofold increase in methionine. Carrillo-Carrasco et al. teach “this suggests that higher OHCbl doses might be required to achieve an optimal biochemical response in cblC patients” (p.728, right col., first para). Carrillo-Carrasco et al. teach treatment goals in patients with cblC should include normalizing biochemical parameters.
While Carrillo-Carrasco et al. teach administering a high-dose of OHCbl to a child with a cblC deficiency, and retinal degeneration, Carrillo-Carrasco et al. do not expressly disclose administering a high-dose of MeCbl (present claim 1).
Chang et al. teach the use of a vitamin supplement composition formulated for treating vitamin deficiency (abstract; claim 1). Vitamin B is included in the supplement, and can be formulated as cyanocobalamin or methylcobalamin (para [0012]; [0034]; claim 8), and administered at a dosage of about 1500 to about 6250 µg (equivalent to about 1.5 to about 6.25 mg; para [0010]; claim 1).
Ogden et al. teach the average weight of a 13 year old child was 63.9 kg (see Table 2).
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 high-dose of MeCbl, and in combination with OHCbl to treat a child with a cblC deficiency and suffering from retinal degeneration.
According to MPEP 2144.06: “It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).
Combining known therapies into a single therapy is a commonly applied method for identifying improved therapeutic outcomes with minimal adverse effect for the patient because each monotherapy is already known to be effective. Here, both MeCbl and OHCbl have been taught for treating cobalamin deficient patients.
The ordinary artisan would have been motivated to optimize and increase the daily dosage of MeCbl as done by Carrillo-Carrasco et al. Administering 10 mg cobalamin per day to a patient having an average weight of 63.9 kg, results in a dosage of 0.15 mg/kg/day. Administering 20 mg cobalamin per day to a patient having an average weight of 63.9 kg, results in a dosage of 0.31 mg/kg/day. A dosage of 0.31 mg/kg/day reads on the range “about 0.3 mg/kg/day” in claim 1.
With respect to administering a high-dose of MeCbl, the amount of MeCbl taught by Chang et al. for the treatment of vitamin deficiency overlaps with the range recited in present claim 21. One having ordinary skill in the art would have been motivated to optimize the concentration further, in view of the teachings by Carrillo-Carrasco et al., because a daily high dose of an alternative cobalamin derivative, OHCbl at 20 mg/day was dose-dependently effective in improving MMA plasma concentrations and tHcy levels. Carrillo-Carrasco et al. teach “this suggests that higher OHCbl doses might be required to achieve an optimal biochemical response in cblC patients” (p.728, right col., first para). Carrillo-Carrasco et al. teach treatment goals in patients with cblC should include normalizing biochemical parameters.
With respect to the amended claimed ranges, and newly added claimed ranges in new claims 40 and 41, see MPEP 2144.05(II), “Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical.”.
The recitation “wherein retinal function is improved in the human subject following the administering” in present claim 6 necessarily occurs upon performing the positively recited steps.
The limitation “further comprising performing an assay on a biological sample from the subject” in claim 23 is met where Carrillo-Carrasco et al. teach measuring MMA and tHcy levels.
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
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