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 .
DETAILED ACTION
This office action is in response to applicant’s reply filed on March 3, 2026.
Restrictions/Elections.
Applicant's election with traverse of Group I (Claims 16-21) in the reply filed on March 3, 2026, is acknowledged.
The traversal is on the ground(s) that the examiner has not established that it would pose an undue burden to examine the full scope of the claimed invention. This is not found persuasive because the above is not a criteria for applications filed under 35 USC 121 and 372.
The requirement is still deemed proper and is therefore made FINAL.
Status of Claims
Claims 16-30 are currently pending and are the subject of this office action.
Claims 22-30 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected inventions, there being no allowable generic or linking claim. Election was made with traverse in the reply filed on March 3, 2026.
Claims 16-21 are presently under examination.
Priority
The present application is a 371 of PCT/EP2023/237484 filed on 06/05/2023 and claims priority to foreign application EPO EP22177932.5 filed on 06/08/2022.
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.
Claim 19 is 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.
Claim 19 recites: “comprising 200-400 mol % citrate”
How can a single component be more than 100% mol of the composition?
The metes and bounds of claim 19 are not clearly defined.
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.
Claim(s) 16-18 and 20-21 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Moser et. al. (US 10,570,134).
NOTE: for this rejection it is being assumed that the process of lyophilization removes most of the water present in the original solution is removed, leaving only traces of water.
For claims 16-17 and 20, Moser teaches a water solution consisting of (see column 25, Example 1-5 (a) Lyophilizate for reconstitution to be used for intravenous application):
18,480 g water
1,386 g sodium hydroxide 2M
969 g sodium citrate tri-hydrate
474 g 5,10-methylene (6R)-tetrahydrofolic acid hemisulfate
210 g water
122 g sodium hydroxide 2M, and
204 g water
The following molecular weights (MW) are being used for the calculations below:
MW 5,10-methylene (6R)-tetrahydrofolic acid disodium salt = 501 g/mol
MW 5,10-methylene (6R)-tetrahydrofolic acid = 457 g/mol
MW 5,10-methylene (6R)-tetrahydrofolic acid hemisulfate =1,013 g/mol
MW sulfuric acid = 98 g/mol
MW sodium sulfate = 142 g/mol
MW sodium hydroxide = 40 g/mol
MW sodium citrate trihydrate = 312 g/mol
MW sodium citrate = 258 g/mol
After mixing all these components, sodium hydroxide will react with the 5,10-methylene (6R)-tetrahydrofolic acid hemisulfate to form 5,10-methylene (6R)-tetrahydrofolic acid disodium salt and sodium sulfate with following stoichiometry:
1- Total amount of sodium hydroxide 2M
1,386 g + 122 g = 1,508 g of sodium hydroxide 2M = 1.5 L of sodium hydroxide 2M
1.5 L x 2 mol/L = 3 mol sodium hydroxide
2- total amount of sulfuric acid and 5,10-methylene (6R)-tetrahydrofolic acid
474 g 5,10-methylene (6R)-tetrahydrofolic acid hemisulfate / 1,013 g/mol = 0.480 mol of 5,10-methylene (6R)-tetrahydrofolic acid hemisulfate, which is equivalent to:
0.480 mol of sulfuric acid, and
0.960 mol of 5,10-methylene (6R)-tetrahydrofolic acid
3- the 0.480 mol of sulfuric acid will react with 0.960 mol of sodium hydroxide to afford 0.480 mol of sodium sulfate
0.480 mol sodium sulfate x 142 g/mol = 68 g sodium sulfate
4- the 0.960 mol of 5,10-methylene (6R)-tetrahydrofolic acid will react with 1.920 mol of sodium hydroxide to afford 0.960 mol of 5,10-methylene (6R)-tetrahydrofolic acid disodium salt
0.960 mol of 5,10-methylene (6R)-tetrahydrofolic acid disodium salt x 501 g/mol = 481 g of 5,10-methylene (6R)-tetrahydrofolic acid disodium salt
5- amount of sodium hydroxide left
+ 3.000 mol (original amount)
– 0.960 mol (reacted with sulfuric acid)
– 1.920 mol (reacted with 5,10-methylene (6R)-tetrahydrofolic acid)
= 0.102 mol of sodium hydroxide left
0.120 mol of sodium hydroxide x 40 g/mol = 5 g of sodium hydroxide
6- total amount of sodium citrate
969 g sodium citrate tri-hydrate x 312 g/mol = 3.1 mol of sodium citrate tri-hydrate, which is equivalent to:
3.1 mol of sodium citrate
3.1 mol of sodium citrate x 258 g/mol = 800 g of sodium citrate
In summary, the solution disclosed by Moser will contain:
Approximately 18,894 g of water (18, 480 g + 210 g + 204 g)
800 g sodium citrate
68 g sodium sulfate
481 g of 5,10-methylene (6R)-tetrahydrofolic acid disodium salt, and
5 g of sodium hydroxide
If one assumes that most of the water is removed by lyophilization, then the lyophilized composition will consist of:
800 g sodium citrate
68 g sodium sulfate
481 g of 5,10-methylene (6R)-tetrahydrofolic acid disodium salt, and
5 g of sodium hydroxide, and
Water (traces)
TOTAL = 1354 g of lyophilized composition
481 g of 5,10-methylene (6R)-tetrahydrofolic acid disodium salt / 1354 g) x 100 = 35.5 % w/w of 5,10-methylene (6R)-tetrahydrofolic acid disodium salt, which anticipates the weight percentage of claims 16 and 20.
Finally, the composition does not contain any further reducing agents or antioxidants. Moser further states that the stabilization of these compositions can be achieved without additional reducing agents (antioxidants) and without the exclusion of atmospheric oxygen (see column 1, lines 27-30).
For claim 18, the molar ratio
5,10-methylene (6R)-tetrahydrofolic acid disodium salt / sodium sulfate is:
(0.960 / 0.480) x 100 = 200%
Which anticipates the instantly claimed range
For claim 21, Moser teaches that when it comes to the stability of the original 5,10-methylene (6R)-tetrahydrofolic acid hemisulfate salt, the highest purity is preferable including 100% or greater than 99.5% pure (see column 3, line39 through column 5, line 21; see also column 36, lines 36-39), all this will result in the disodium salt of 5,10-methylene (6R)-tetrahydrofolic acid being 100% pure or at least 99.5% pure.
Conclusion
No claims are allowed.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARCOS L SZNAIDMAN whose telephone number is (571)270-3498. The examiner can normally be reached on Flexing M-F 7 AM-7 PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Amy L. Clark can be reached on 571 272-1310. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MARCOS L SZNAIDMAN/
Primary Examiner, Art Unit 1628
March 5, 2026.
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