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 .
Status of Claims
Claims 39-51 are pending in the instant application. Claim 50 is amended via the amendment filed June 22nd, 2026.
Withdrawn Rejections
Applicant’s arguments, filed June 22nd, 2026, with respect to the rejection of claims 50-51 under 35 U.S.C. 102(a)(1) have been fully considered and are persuasive. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of Applicant’s amendment providing a different interpretation of the previously applied reference.
Applicant has overcome this rejection by amending claim 50 to specify that the composition is administered daily.
Maintained Rejections
Applicant's arguments filed June 22nd, 2026 with respect to the 35 U.S.C. 103 rejection of claims 47-49 as being obvious over Vermeer in view of Tak have been fully considered but they are not persuasive.
See response to remarks.
Response to Remarks
Applicant’s remarks regarding the 35 U.S.C. 102(a)(1) rejection of claims 50-51 will only be addressed as they apply to the newly necessitated rejection due to Applicant’s amendment.
On p. 2-3 of the remarks, Applicant argues that the dosing regimen is materially different from Caluwe as the newly amended claims require that the composition is administered daily. Examiner acknowledges this issue and addresses the new limitation in the rejection below, necessitated by Applicant’s amendment.
On p. 3 of the remarks, Applicant argues that Caluwe’s method is directed to treating patients on chronic hemodialysis while claim 50 recites “administering to subject in need thereof” for treating oxidative stress or increasing ATP production.
In response, patients on chronic hemodialysis are also patients who experience oxidative stress. This is made evident with a citation provided for evidentiary purposes in the necessitated rejection below.
On p. 4 of the remarks, Applicant argues that the phrase “whereby reactive oxygen species are reduced, or ATP product is increase by at least 10%” is a nonlimiting statement as there is a specific, quantitative threshold.
However, this argument is still not persuasive. As stated in the previous Office action, the clause of the instant disclosure “whereby reactive oxygen species are reduced or ATP production is increased by at least 10%”, simply expresses the intended result of a process step positively recited. The process step being the administration of vitamin K and rivaroxaban to a cell and the intended result being that ATP production is increased by at least 10%.
As stated above, Applicant’s arguments regarding the rejection under 35 U.S.C. 103 have been fully considered, but are not persuasive.
On p. 1 of the remarks, Applicant argues that Examiner’s reasoning rests on an erroneous conflation of DOMS with thrombosis. Applicant argues that DOMS and thrombosis are different conditions with different etiologies.
Examiner acknowledges that they are different conditions, however, they are intertwined as taught by Tak. As stated in the previous Office action, Tak teaches that leg pain after exercise is a symptom and should be used as a diagnostic tool of thrombosis. As the composition of the instant invention is known to treat thrombosis, a PHOSITA would recognize that treating thrombosis would also treat symptoms of thrombosis, and as taught by Tak, one of those symptoms includes leg pain after exercise.
On p. 1-2 of the remarks, Applicants argues that Tak is silent on DOMS. Applicant agues that Tak only teaches that a patient who developed leg pain and swelling after walking for 25 km in a day, the patient was also diagnosed with thrombosis.
In response, as Applicant does not provide a definition of DOMS in the instant disclosure, Examiner has looked to the art for the definition recognizable to a person of ordinary skill in the art. For instance, delayed-onset muscle soreness (DOMS) describes muscle pain and tenderness that typically develop several hours postexercise, as evidenced by Zainuddin (J Athl Train. 2005 Jul-Sep;40(3):174–180). Thus, as Tak teaches that a patient with thrombosis also experienced leg pain and swelling after walking, Tak alludes to DOMS, as defined in the art.
In view of the above, the 103 rejection of claims 47-49 is maintained.
Restriction/Election
Search and examination has been limited as previously discussed in the Office action dated November 18th, 2024. Examination is limited to the extent that claims 47-51 are readable on elected group II, with the elected anticoagulant, rivaroxaban. Since the elected species is not allowable, subject matter not embraced by the elected embodiment is therefore withdrawn from further consideration, claims 39-46 are withdrawn.
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.
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.
Claim(s) 47-49 stand rejected under 35 U.S.C. 103 as being unpatentable over Vermeer et al (US 2016/0310445, as cited on the IDS dated 09/20/2021) in view of Tak et al (BMJ Case Rep 2013. doi:10.1136/bcr-2013-201488).
Determining the scope and contents of the prior art. (See MPEP § 2141.01)
Vermeer teaches vitamin K for use in a method for preventing and/or decreasing and/or counteracting thrombosis risk, in mammalian subjects, preferably human subjects (claim 1). Vermeer teaches that the vitamin K is a menaquinone, preferably a long chain menaquinone, MK-7 (claim 3). Vermeer also teaches that the vitamin K is for administration in combination with factor Xa inhibitors and/or heparin-related anticoagulants (claim 15). Further, Vermeer teaches that the factor Xa inhibitor is rivaroxaban (paragraph [0068]).
Ascertainment of the differences between the prior art and the claims. (See MPEP § 2141.02)
The prior art does not explicitly teach that the mammals to be treated with the vitamin K2 and rivaroxaban composition also experience delayed onset muscle soreness associated with exercise.
Finding of prima facie obviousness --- rationale and motivation (See MPEP § 2142-2143)
However, Tak teaches that leg pain after heavy repetitive exercise is a symptom of thrombosis. Tak teaches that a patient developed leg pain and swelling after walking for exercising (page 1, right column, paragraph 1). Tak teaches that the patient was diagnosed with thrombosis (summary). Further, Tak teaches that thrombosis should be kept as differential in patients who develop lower leg swelling and pain after heavy repetitive exercise (page 2, right column, paragraph 4).
Regarding claim 47, one of ordinary skill in the art would have been motivated to administer vitamin K2 and rivaroxaban as a method of treating delayed onset muscle soreness as Vermeer teaches that the combination treats thrombosis and Tak teaches that leg pain after exercise is a symptom and should be used as a diagnostic tool of thrombosis.
Regarding claims 48-49, as seen above, Vermeer teaches that the anticoagulant is rivaroxaban.
Claim(s) 50-51 are newly rejected under 35 U.S.C. 103 as being unpatentable over Caluwe R et al. (Clin Kidney J. 2016 Apr;9(2):273-9), as evidenced by Liakopoulos (Oxid Med Cell Longev. 2017:2017:3081856. doi: 10.1155/2017/308185).
Determining the scope and contents of the prior art. (See MPEP § 2141.01)
Clauwe teaches a method of treating patients on chronic hemodialysis, with non-valvular atrial fibrillation, using a combination of Rivaroxaban 10 mg od + MK-7 2000 μg 3x/w (page 275, left column, paragraph 1). In Table 1, Caluwe discloses that MK-7 can be administered at various does, each targeting specific cardiovascular disease states: 180 ug daily for arterial stiffness, 375 ug daily for arterial stiffness, mineral density, and insulin sensitivity, and 2000 three times weekly for progression of thoracic aorta and arterial stiffness (page 276).
Patients on hemodialysis also experience oxidative stress. Oxidative stress appears in early chronic kidney disease (CKD), advances along with worsening of renal failure, and is further exacerbated by the hemodialysis process, as evidence by Liakopoulos (Oxid Med Cell Longev. 2017:2017:3081856.
doi: 10.1155/2017/308185).
Regarding claim 50, the phrase “whereby reactive oxygen species are reduced or ATP production is increased by at least 10%.”” is a nonlimiting statement of intended purpose. Generally, a “wherein”, “whereby” or “thereby” clause in a method claim “is not given weight when it simply expresses the intended result of a process step positively recited.” Minton v. Nat’l Ass’n of Securities Dealers, Inc., 336 F.3d 1373, 1381 (Fed. Cir. 2003). See MPEP 2111.04(I).
Ascertainment of the differences between the prior art and the claims. (See MPEP § 2141.02)
Caluwe does not explicitly teach that the composition is administered daily.
Finding of prima facie obviousness --- rationale and motivation (See MPEP § 2142-2143)
However, as seen above, Caluwe discloses that MK-7 can be administered at various does, each targeting specific cardiovascular disease states: 180 ug daily for arterial stiffness, 375 ug daily for arterial stiffness, mineral density, and insulin sensitivity, and 2000 three times weekly for progression of thoracic aorta and arterial stiffness (page 276). Further, Caluwe teaches that the rivaroxaban can be administered as a daily dosage (abstract).
As Caluwe teaches dosages of MK-7 and rivaroxaban that are formulated to be administered daily, one of ordinary skill in the art would have been motivated to optimize the teachings of Caluwe and administer the combined composition daily.
Also, see MPEP 2144.04: 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. "[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) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 ("The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages."); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Lab. Inc., 874 F.2d 804, 809, 10 USPQ2d 1843, 1848 (Fed. Cir. 1989), cert. denied, 493 U.S. 975 (1989)(Claimed ratios were obvious as being reached by routine procedures and producing predictable results); In re Kulling, 897 F.2d 1147, 1149, 14 USPQ2d 1056, 1058 (Fed. Cir. 1990)(Claimed amount of wash solution was found to be unpatentable as a matter of routine optimization in the pertinent art, further supported by the prior art disclosure of the need to avoid undue amounts of wash solution); and In re Geisler, 116 F.3d 1465, 1470, 43 USPQ2d 1362, 1366 (Fed. Cir. 1997)(Claims were unpatentable because appellants failed to submit evidence of criticality to demonstrate that that the wear resistance of the protective layer in the claimed thickness range of 50-100 Angstroms was "unexpectedly good"); Smith v. Nichols, 88 U.S. 112, 118-19 (1874) (a change in form, proportions, or degree "will not sustain a patent"); In re Williams, 36 F.2d 436, 438, 4 USPQ 237 (CCPA 1929) ("It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions."). See also KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416, 82 USPQ2d 1385, 1395 (2007) (identifying "the need for caution in granting a patent based on the combination of elements found in the prior art.").
Conclusion
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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/A.G.K./Examiner, Art Unit 1626
/FEREYDOUN G SAJJADI/Supervisory Patent Examiner, Art Unit 1699
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