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 .
Election/Restrictions
Applicant’s election without traverse of:
Group I; and
Species Election: the dosage form of said preparation is a drop in the reply filed on November 10, 2025 is acknowledged.
The Examiner respectfully notes the elected Group I and the elected species of a drop read on claims 1-5 and 8-9.
Claims 6-7 and 10-18 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species and invention, respectively, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on November 10, 2025.
Claim Status
The claim set filed April 03, 2023 has been entered. Claims 6-7 and 10-18 are withdrawn from further consideration as being drawn to a nonelected species or invention respectively as discussed in greater detail in the Election/Restrictions section above.
Thus, claims 1-5 and 8-9 are examined on the merits herein.
Claim Objections
Claims 2 and 9 are objected to because of the following informalities:
Claim 2, line 2, and Claim 9, line 2 each recite “and the methylcobalamin ophthalmic preparation” resulting in the recitation of a superfluous “and” immediately before the word “the”. Thus, to promote clarity and flow of the claim the Examiner respectfully suggests deleting the word “and” as discussed above.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-5 and 8-9 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
(I) Regarding claim 1, the claim requires a methylcobalamin ophthalmic preparation comprising a methylcobalamin technical (TC) and proanthocyanidin, see lines 1-2. Claim 1 also recites the methylcobalamin technical (TC) and proanthocyanidin have a mass ratio within said preparation of (0.02-0.1):(0-0.5), see lines 2-3.
The Examiner respectfully notes the limitation (0-0.5) within the mass ratio corresponds to the proanthocyanidin within said preparation. Additionally, the Examiner respectfully notes the ratio explicitly includes the value of zero (i.e. 0) within the specified range for the mass of the proanthocyanidin within the preparation.
The Examiner respectfully notes a valid ratio based on this recitation for the preparation could be for example where the mass of the methylcobalamin technical (TC) is within the range of 0.02-0.1 parts to 0 parts proanthocyanidin.
As a result said example illustrates when there is 0 parts proanthocyanidin within the preparation, said preparation does not require proanthocyanidin.
The Examiner also respectfully notes this interpretation is supported multiple times within the specification see for example in paragraphs [0008]; [0035]; and [0039].
The Examiner further particularly notes the mass range for proanthocyanidin within the preparation could preferably be (0.1-0.5) and more preferably be (0.2-0.4), see specification, paragraph [0039]. Therefore, this recitation within the specification further supports the Examiner’s reasonable interpretation that said preparation does not require proanthocyanidin.
However, as discussed above within claim 1, lines 1-2, the claim recites said preparation comprises methylcobalamin technical (TC) and proanthocyanidin. However, in view of the mass ratio where the limitation (0-0.5) corresponds to the proanthocyanidin where said limitation explicitly includes the value of zero (i.e. 0) as a mass for the proanthocyanidin within the preparation, it is thus unclear and indefinite in view of the foregoing reasons above whether or not proanthocyanidin is a required component within the preparation recited in claim 1.
Therefore, in the interest of compact prosecution and in view of the recitations of “preferably be (0.1-0.5) and more preferably be (0.2-0.4)” within paragraph [0039] of the specification when referring to the mass of proanthocyanidin within the ophthalmic preparation, the Examiner reasonably interprets the limitations of “proanthocyanidin” and “wherein the methylcobalamin technical (TC) and proanthocyanidin have a mass ratio of (0.02-0.1):(0-0.5)” are optional limitations and thus are not required by claim 1.
Thus, the Examiner reasonably interprets and will search the prior art where claim 1 requires a methylcobalamin ophthalmic preparation comprising a methylcobalamin technical (TC) in the dosage form recited in claim 1 and elected by Applicant within the Election/Restriction section above.
Claims 2-5 and 8-9 are included in this rejection as they either depend from or rely on the preparation of claim 1.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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.
(I) Claims 1 and 8 are rejected under 35 U.S.C. 103 as being unpatentable over Kanemoto (Published 03 December 2020, WO-2020241374-A1, English Machine Translation, PTO-892) in view of Frisbie et al. (Published 01 December 1993, Biochemistry, Vol. 32, Issue 50, pp. 13886-13892, PTO-892).
Regarding claims 1 and 8, Kanemoto teaches a composition comprising a vitamin B12 compound where the decomposition of the vitamin B12 compound by light exposure is inhibited, see pg. 3, vitamin B12-containing composition, paragraph 5.
Kanemoto teaches the decomposition of the vitamin B12 compound can be suppressed even if the composition is exposed to light under severe conditions and an extremely remarkable effect of photostabilizing the vitamin B12 compound can be achieved, pg. 1, abstract (English).
Kanemoto teaches the vitamin B12 compound refers to vitamin B12 (cyanocobalamin), its derivatives, and salts thereof, for example derivatives include methylcobalamin, see pg. 4, vitamin B12, paragraph 1.
Kanemoto teaches the product form of the compositing containing the vitamin B12 compound includes pharmaceuticals, see pg. 9, shape-product forms such as vitamin B 12 analog-containing composition, paragraph 5.
Kanemoto teaches examples of pharmaceuticals include eye drops, (i.e. the ophthalmic preparation, required in claim 1, line 1; and the dosage form of a drop, required in claim 1, lines 3-4), see pg. 9, shape-product forms such as vitamin B 12 analog-containing composition, paragraph 8.
Kanemoto teaches the vitamin B12 containing composition is an aqueous composition, the pH thereof is, for example, 4.0 to 8.0 (e.g. the pH of the methylcobalamin ophthalmic preparation, see claim 8), see pg. 9, shape-product forms such as vitamin B 12 analog-containing composition, paragraph 3.
Kanemoto also teaches it is desired to develop a new technology for photostablizing vitamin B12, see pg. 3, vitamin B12-containing composition, paragraph 3.
Although, Kanemoto does not teach the methylcobalamin is the methylcobalamin technical (TC) as required in claim 1, lines 1-2.
However, in the same field of endeavor of photostabilizing vitamin B12, Frisbie teaches human cobalophilin bound to methylcobalamin and a functional role in protecting methylcobalamin from photolysis, see pg. 13886, title.
Frisbie teaches photolysis of the photolabile methyl-cobalt bond shows a significant stabilizing effect by the protein reflected in a lowering of the quantum yield from 0.35 ± 0.04 for free methylcobalamin to 0.0055 ± 0.0004 for the cobalophilin-methylcobalamin complex (e.g. the methylcobalamin technical (TC), required in claim 1, lines 1-2), see pg. 13886, abstract.
Frisbie teaches the photostablizing effect may be physiologically significant in stabilizing methylcobalamin in vivo and indicates an important and previously unknown function for cobalophilin, see pg. pg. 13886, abstract.
Frisbie teaches human cobalophilin is a glycoprotein found in virtually every human biological fluid, see pg. 13886, left column, paragraph 1.
Frisbie teaches human cobalophilin has a role as a vitamin B12 transporter, see pg. 13887, left column, paragraph 2.
Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the invention was filed to have modified the vitamin B12-containing composition taught by Kanemoto by including the human cobalophilin as taught by Frisbie above in order to form the methylcobalamin-cobalophilin complex taught by Frisbie as within the scope of the artisan as combining prior art elements according to known compositions to yield predictable results.
One of ordinary skill in the art would have been motivated to provide the cobalophilin of Frisbie into the composition of Kanemoto as discussed above in order to provide a photostablizing effect for the methylcobalamin in vivo, as Kanemoto teaches it is desired to develop new technology for photostablizing vitamin B12, for example the methylcobalamin as taught by Kanemoto.
One of ordinary skill in the art would have had a reasonable expectation of success to have incorporated the cobalophilin as taught by Frisbie into the composition comprising methylcobalamin as taught by Kanemoto in order to form the methylcobalamin-cobalophilin complex taught by Frisbie, as Kanemoto and Frisbie are drawn to compositions comprising methylcobalamin where an extremely remarkable effect of photostabilizing vitamin B12 can be achieved; wherein Frisbie specifically teaches methylcobalamin as the form of vitamin B12; and wherein Frisbie teaches cobalophilin is a human glycoprotein found in virtually every human biological fluid as a transporter of vitamin B12 as discussed above.
Thus, the claimed invention as a whole would have been prima facie obvious over the combined teachings of the prior art.
(II) Claims 2-5 and 9 are rejected under 35 U.S.C. 103 as being unpatentable over Kanemoto (Published 03 December 2020, WO-2020241374-A1, English Machine Translation, PTO-892) in view of Frisbie et al. (Published 01 December 1993, Biochemistry, Vol. 32, Issue 50, pp. 13886-13892, PTO-892) as applied to claims 1 and 8 above, and further in view of Kentaro (Published 11 April 2019, WO-2019069966-A1, English Machine Translation, PTO-892) and Singh Rawat et al. (Published 20 December 2020, WO-2021124301-A1, PTO-892).
Kanemoto and Frisbie address claims 1 and 8 as written above. Kanemoto further teaches the concentration of vitamin B12 within the vitamin B12-containing composition is for example 0.0001 to 0.2% by weight, (e.g. the percentage of methylcobalamin TC, required in claim 2, line 4.), see pg. 4, vitamin B12, paragraph 2.
Kanemoto teaches the vitamin B12-containing composition contains various pharmacological components, for example water, pH adjusters, buffers and antioxidants and where these components may be used in combination of two or more, see pp. 8-9, other ingredients, paragraph 1.
Kanemoto teaches the vitamin B12-containing composition may further contain a polyhydric alcohol, for example propylene glycol and glycerin (e.g. the osmotic pressure regulator, required in claim 4), where propylene glycol is preferred, see pg. 8, multivalent alcohol, paragraphs 1-2.
Although, Kanemoto does not teach the concentrations of the proanthocyanidin, the buffer, the osmotic pressure regulator, or the pH regulator, required in claim 2, lines 5-8.
However, in the same field of endeavor of ophthalmic formulations, Kentaro teaches a composition for retinal and/or optic nerve protecting comprising a processed product of pine bark, see pg. 7, aspect c1; wherein said composition is a pharmaceutical composition, see pg. 7, aspect c5.
Kentaro teaches pine bark is rich in polyphenols with antioxidant activity such as proanthocyanidins, see pg. 6, fifth paragraph from the bottom of the page.
Kentaro teaches an amount of proanthocyanidin within said composition can preferably be for example 0.5 to 500 mg, see pg. 10, paragraph 5.
Kentaro teaches the dosage form of the pharmaceutical includes eye drops, see pg. 12, second paragraph from the bottom of the page.
The Examiner respectfully notes within a 100 gram composition of Kanemoto, if the amount of the proanthocyanidin, taught as an antioxidant by Kentaro, was provided within the composition of Kanemoto at an amount of 100-500 mg, it would be 0.1-0.5 g, and therefore would correspond to a mass percentage of 0.1%-0.5% as required by the percentage of proanthocyanidin required in claim 2, line 5.
Additionally, Singh Rawat teaches an ophthalmic formulation comprising at least one component selected from the group consisting of and including a buffering agent, a tonicity modifier, a pH modifier, and an antioxidant, see abstract. Singh Rawat teaches the form of the ophthalmic formulation may be for example eye drops, see paragraph [000177].
Singh Rawat teaches exemplary buffering agents include salts (e.g. sodium, potassium, etc.) acids or bases, where appropriate, and include phosphate and citrate, see paragraph [000152], pg. 39.
The Examiner respectfully notes the buffering agents taught by Singh Rawat make obvious disodium hydrogen phosphate, sodium dihydrogen phosphate, potassium dihydrogen phosphate and sodium citrate required in claim 3.
Singh Rawat teaches the ophthalmic formulation where the buffering agent is present in an amount of about 0.005% to 5% w/v or w/w of the formulation (e.g. the percentage of buffer, required in claim 2, line 6), see paragraph [00082].
Singh Rawat exemplifies the tonicity modifier as glycerin and propylene glycol (e.g. the osmotic pressure regulator, required in claim 4), see paragraph [000159]. Singh Rawat teaches the ophthalmic formulation where the tonicity modifier is present in an amount of about 0.005% to 5% w/v or w/w of the formulation (e.g. the percentage of osmotic pressure regulator, required in claim 2, line 7).
Singh Rawat teaches the formulations will have a tonicity modifier in an amount sufficient to cause the final composition to have an ophthalmically acceptable osmolarity, for example, about 250 to about 350 mOsM/L, see paragraph [000160].
The Examiner respectfully notes the osmolarity of about 250 to about 350 mOsM/L taught by Singh Rawat corresponds to w/v formulations; and when the formulation is a w/w formulation the Examiner reasonably interprets the unit is mOsM/kg as both w/v and w/w formulations are taught by Singh Rawat above, and thus the Examiner respectfully notes this interpretation would correspond to the osmolarity required in claim 9.
Singh Rawat exemplifies the pH modifier as either sodium hydroxide or hydrochloric acid (e.g. the pH regulator, required in claim 5), see Table F, pp. 59-60. Singh Rawat teaches the pH modifier can be used at an amount of from about 0.001 to about 1.0% w/v or w/w (e.g. the concentration of the pH regulator, required in claim 2, line 8), see paragraph [000153], pg. 40.
With respect to the limitation “water for injection, as a balance”, required in the last line of claim 2. The Examiner reasonably interprets this as a physical limitation that is taught by the combination of Kanemoto, Kentaro and Singh Rawat as each reference teaches ophthalmic formulations that are eye drops; Kanemoto teaches the formulation contains water and has the mass percentage of methylcobalamin TC required in claim 2; Kentaro teaching the mass percentage of proanthocyanidin in claim 2; and Singh Rawat teaching the mass percentage of the buffer, osmotic pressure regulator and pH regulator as required in claim 2.
Thus, the limitation of “water for injection, as a balance” as interpreted by the Examiner above would be well within the scope of the artisan and met based on the teachings of Kanemoto, Kentaro and Singh Rawat as discussed above.
It would have been prima facie obvious to one of ordinary skill in the art before the invention was filed to have incorporated the teachings of Kentaro and Singh Rawat as discussed above as within the scope of the artisan as combining prior art elements according to known compositions to yield predictable results. One of ordinary skill in the art would have been motivated to provide the percentages of water, pH adjusters, buffers, antioxidants and polyhydric alcohol within the composition as taught by Kanemoto above. One of ordinary skill in the art would have had a reasonable expectation of success to incorporate the teachings of Kentaro and Singh Rawat into the composition of Kanemoto above; as Kanemoto, Kentaro and Singh Rawat are all drawn to ophthalmic formulations where each specifically exemplify eye drops as discussed above.
Thus, the claimed invention as a whole would have been prima facie obvious over the combined teachings of the prior art.
Conclusion
No claims are allowed in this action.
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/JARET J CREWS/Examiner, Art Unit 1691
/SAVITHA M RAO/Primary Examiner, Art Unit 1691