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 .
The amendment filed 04/29/2026 has been received, entered and considered. The following information has been made of record in the instant amendment:
1. Claims 1-18, 22, and 25 have been canceled.
2. New Claims 29-30 have been added.
3. Claims 19, 23-24, and 27-28 have been amended.
4. Remarks drawn to rejections under 35 USC 112, 102, 103 and double patenting.
The following objection(s)/rejection(s) has/have been overcome:
5. The rejection of claims 19-28 under 35 U.S.C. 112(a), for lack of enablement for prevention of cognitive decline in the elderly has been overcome by deletion of the term preventing.
6. The rejection of Claims 23 and 25 on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-5, 12-15 and 17 of U.S. Patent No. 10,821,130 (‘130) in view of Smith et al (PLoS One, 2010, 5(9), 1-10; of record) has been rendered moot by cancelation.
7. The rejection of Claim(s) 19-21 and 25-27 under 35 U.S.C. 102(a)(1) as being anticipated by Smith et al (PLoS One, 2010, 5(9), 1-10), and the rejection of Claims 19-21 and 26-28 under 35 U.S.C. 103 (a) as being unpatentable over Miller (US 2015/0086625) in view of Hendricks (US Patent 6,790,462) and further in view of Smith et al (PLoS One, 2010, 5(9), 1-10), and the rejection of Claim(s) 22-24 under 35 U.S.C. 103 as being unpatentable over Miller (US 2015/0086625) in view of Hendricks (US Patent 6,790,462) and further in view of Smith et al (PLoS One, 2010, 5(9), 1-10) and Petrus (US 8,486,889) have been withdrawn in view of the amendment, and replaced by the rejection below.
Claims 19-21, 23-24, and 26-30 are pending in the case.
The following rejections are necessitated by Applicant's amendment filed 04/29/2026 wherein the limitations in pending claims 19, 23-24, and 27-28 have been amended. Claim 19 has been amended to include the limitations of claims 22 and 25. Support for new claims 29-30 is seen at para 0213 in the published application US 20240041915 A1.
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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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.
Claim(s) 19-21, 23-24, and 26-30 are rejected under 35 U.S.C. 103 as being unpatentable over Smith et al (PLoS One, 2010, 5(9), 1-10; of record) in view of Petrus (US 8,486,889; of record).
Smith et al teaches a method of reducing cognitive impairment in an elderly subject by administering vitamin B6 (20mg/day), vitamin B12 and folic acid (vitamin B9, 0.8mg/day) (Abstract; method of claim 19, and limitations of claim 19 regarding subject, active agent and dosage; elderly human subject as in claim 20; dosage as in claim 25 and vitamin B12 and vitamin B9 (folic acid) as in claim 26). The elderly subjects were given tablets containing the active agents (page 2, right col. third full para; oral administration as in claim 21).
Even though Smith does not teach the dosage of vitamin B12 as in claim 28, it teaches administration of 0.5mg/day of vitamin B12. In view of this teaching one of ordinary skill can use this as a starting point and adjust the dosage range of vitamin B12 as in claim 28 in order to provide a dosage range that is effective for reducing cognitive decline.
Smith does not expressly teach the simultaneous administration of a nitric oxide releasing compound as in amended claim 19 and the limitations of claims 23-24.
Petrus teaches that citrulline, an amino acid like arginine, can be converted into nitric oxide. Oral doses for citrulline ranges from 50-600 mg (column 14, lines 1-5; page 20, Table 15). Petrus teaches a composition including Vitamin B6, Vitamin B12 and L-citrulline as well as other ingredients (col. 19, Example 15; col. 21, example 19; nitric oxide releasing compound as in claims 19 and 23, dosage of citrulline as in claim 24, and limitation of claim 26-vitamin B12). Citrulline is suggested as a component with vitamin B6 and B12 in oral tablets to prevent endothelial dysfunction associated with cognitive decline. In view of the teachings of Smith and Petrus it would be obvious to one of ordinary skill in the art to administer the nitric oxide producing compound simultaneously with vitamin B12 in a method of reducing cognitive decline as in amended claim 19. The dosage of citrulline as in claims 29-30 can be adjusted using the dosage taught by Petrus as starting point.
MPEP 2141 states, "The key to supporting any rejection under 35 U.S.C. 103 is the clear articulation of the reason(s) why the claimed invention would have been obvious. The Supreme Court in KSR noted that the analysis supporting a rejection under 35 U.S.C. 103 should be made explicit. The Court quoting In re Kahn, 441 F.3d 977, 988, 78 USPQ2d 1329, 1336 (Fed. Cir. 2006), stated that "[R]ejections on obviousness cannot be sustained by mere conclusatory statements; instead, there must be some articulated reasoning with some rational underpinning to support the legal conclusion of obviousness.'" KSR, 550 U.S. at, 82 USPQ2d at 1396. Exemplary rationales that may support a conclusion of obviousness include: (A) Combining prior art elements according to known methods to yield predictable results; (B) Simple substitution of one known element for another to obtain predictable results; (C) Use of known technique to improve similar devices (methods, or products) in the same way; (D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results; (E) " Obvious to try " choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success; (F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art; (G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention."
According to the rationale discussed in KSR above, the rationale in (G) above is seen to be applicable here since based on the prior art teachings, the claimed vitamins are known in the art to be useful for reducing cognitive decline in a subject. Citrulline is also suggested as a component with Vitamin B6 and B12 for making tablets to prevent endothelial dysfunction associated with cognitive decline.
Thus, the claimed invention as a whole would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention over the combined teachings of the prior art. The artisan would be motivated administer a composition comprising vitamin B6 and a nitric oxide releasing compound like citrulline in a method for reducing or preventing cognitive decline in an elderly subject since citrulline with vitamin B6 and B12 would reduce or prevent cognitive decline and also prevent endothelial dysfunction associated with cognitive decline (Petrus). The artisan can adjust the amounts for obtaining maximum beneficial effects.
It has been held that it is within the skill in the art to select optimal parameters, such as amounts of ingredients in order to achieve a beneficial effect. See In re Boesch, 205 USPQ 215 (CCPA 1980). One of skill in the art would want to adjust the dosage of the active agents including that of citrulline as in claims 29-30 to obtain maximum beneficial effects.
Claims 19-21, 23-24, and 26-30 are rejected under 35 U.S.C. 103 (a) as being unpatentable over Miller (US 2015/0086625; of record) in view of Hendricks (US Patent 6,790,462; of record) and further in view of Smith et al (PLoS One, 2010, 5(9), 1-10; of record) and Petrus (US 8,486,889; of record).
Miller teaches dietary supplement containing vitamins which improve health. The dietary One of the conditions treated using the vitamins is cognitive disorders (paras 0019 and 0038; condition recited in claim 19). The dietary supplement can contain vitamin B-6 and B-12 (para 0013; active agents recited in claims 19, 21 and 26). The composition comprising the vitamins can be administered to humans (para 0033). Even though the method for reducing cognitive decline in an elderly subject is not expressly taught by Miller, one of ordinary skill in the art will recognize that the composition of Miller can be administered to an elderly subject for the same purpose as in claims 19 and 20.
Miller does not teach the simultaneous administration of a nitric oxide releasing compound as in claim 19, the limitations of claims 23-24 and 29-30.
Hendrick teaches that there is evidence that elevated levels of homocysteine (Hcy), an amino acid that is formed as a byproduct of metabolism and is found in blood plasma, provide a better indicator for coronary heart disease than elevated blood cholesterol levels. It has also been found that the B-complex vitamins administered as nutritional supplements can be effective in reducing plasma levels of Hcy. (col. 1, lines 34-44). Hendrick teaches that the supplement composition comprises a dietary supplemental amount of one or more vitamins, such as for example Vitamin B-6 and Vitamin B-12 (col. 2, lines 47-51). Hendrick teaches that elevated levels of Hcy are implicated in many of the diseases associated with aging such as the decline in cognitive abilities, by virtue of the formation of adducts with metabolically important molecules, primarily proteins. This irreversible homocysteinylation leads to a reduction or complete loss of function of these proteins which is time and Hcy concentration dependent. The reduction of Hcy achieved through use of suitably formulated nutritional supplements will retard or prevent the progression of these molecular changes (col. 2, lines 3-10). This provides motivation to make a composition comprising vitamin B6, B12 and administer it in a method of reducing or preventing cognitive decline in an elderly subject. Hendrick teaches 15mg of vitamin B6 and 500mg of vitamin B12 (page 6, Example 2). Using this and the dosage of vitamin B9 taught by Smith as starting points one of ordinary skill in the art can adjust the amounts to mg or g/day for the dosage as in claims 19, and 27-28.
The teachings of Smith et al is set forth above. Smith teaches the use of vitamin B9 also as an active agent in a method of treating cognitive decline in an elderly subject. The dosage of vitamin B9 is 0.8mg/day. The dosage of vitamin B6 is 20mg/day (limitations of claims 19, 26 and 27).
Petrus teaches that citrulline, an amino acid like arginine, can be converted into nitric oxide. Oral doses for citrulline ranges from 50-600 mg (column 14, lines 1-5; page 20, Table 15). Petrus teaches a composition including Vitamin B6, Vitamin B12 and L-citrulline as well as other ingredients (col. 19, Example 15; col. 21, example 19; nitric oxide releasing compound as in claims 19 and 23, dosage of citrulline as in claim 24, and limitation of claim 26-vitamin B12). Citrulline is suggested as a component with vitamin B6 and B12 in oral tablets to prevent endothelial dysfunction associated with cognitive decline. In view of the teachings of Smith and Petrus it would be obvious to one of ordinary skill in the art to administer the nitric oxide producing compound simultaneously with vitamin B12 in a method of reducing cognitive decline as in amended claim 19. One of ordinary skill in the art can adjust the dosage of citrulline as in claim 29-30 using the amount taught by Petrus as a starting point.
It has been held that it is within the skill in the art to select optimal parameters, such as amounts of ingredients in order to achieve a beneficial effect. See In re Boesch, 205 USPQ 215 (CCPA 1980). One of skill in the art would want to adjust the dosage to obtain maximum beneficial effects.
MPEP 2141 states, "The key to supporting any rejection under 35 U.S.C. 103 is the clear articulation of the reason(s) why the claimed invention would have been obvious. The Supreme Court in KSR noted that the analysis supporting a rejection under 35 U.S.C. 103 should be made explicit. The Court quoting In re Kahn, 441 F.3d 977, 988, 78 USPQ2d 1329, 1336 (Fed. Cir. 2006), stated that "[R]ejections on obviousness cannot be sustained by mere conclusatory statements; instead, there must be some articulated reasoning with some rational underpinning to support the legal conclusion of obviousness.'" KSR, 550 U.S. at, 82 USPQ2d at 1396. Exemplary rationales that may support a conclusion of obviousness include: (A) Combining prior art elements according to known methods to yield predictable results; (B) Simple substitution of one known element for another to obtain predictable results; (C) Use of known technique to improve similar devices (methods, or products) in the same way; (D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results; (E) " Obvious to try " choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success; (F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art; (G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention."
According to the rationale discussed in KSR above, the rationale in (G) above is seen to be applicable here since based on the prior art teachings, the claimed vitamins are known in the art to be useful for reducing cognitive decline in a subject, and citrulline is also suggested as a potential active agent for treating cognitive decline since it is a nitric oxide releasing compound.
Thus, the claimed invention as a whole would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention over the combined teachings of the prior art. The artisan would be motivated administer the claimed vitamins and a nitric oxide releasing compound in a method of reducing or preventing cognitive decline in an elderly subject as in claim 19 and dependents thereof since Hendrick teaches that elevated levels of Hcy are implicated in many of the diseases associated with aging such as the decline in cognitive abilities, by virtue of the formation of adducts with metabolically important molecules, primarily proteins. This irreversible homocysteinylation leads to a reduction or complete loss of function of these proteins which is time and Hcy concentration dependent. The reduction of Hcy is achieved through use of suitably formulated nutritional supplements will retard or prevent the progression of these molecular changes (col. 2, lines 3-10). This provides motivation to make a composition comprising vitamin B6, B12 and B9 and administer it in a method of reducing cognitive decline in an elderly subject.
Response to Applicant’s Remarks
Regarding the rejection of claims 22-24 and 28 under 35 USC 103 over Smith in view of Petrus, and the rejection of claims 19-21 and 26-28 under 35 USC 103 over Miller in view of Hendricks and Smith, and the rejection of claims 22-24 under 35 USC 103 over Miller in view of Hendricks, Smith and Petrus applicant has argued that independent claim 19 has been amended to incorporate the subject matter of dependent claim 25, which is not included in any of the obviousness rejections. Applicant requests that the obviousness rejections of the present claims be reconsidered and withdrawn (page 5-Remarks).
In response the Examiner states that claim 25 was not included in any of the obviousness rejections because it was rejected under 35 USC 102 over Smith, and claim 22 was rejected under 35 USC 103 over Smith and Petrus. Now that the limitation of claim 25 has been incorporated into independent claim 19, independent claim 19 is now rejectable under 35 USC 103 as set forth above. The pending claims are still rendered obvious in view of the amendment.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory obviousness-type double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); and In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on a nonstatutory double patenting ground provided the conflicting application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement.
Effective January 1, 1994, a registered attorney or agent of record may sign a terminal disclaimer. A terminal disclaimer signed by the assignee must fully comply with 37 CFR 3.73(b).
The USPTO Internet website contains Terminal Disclaimer forms which may be used. Please visit www.uspto.gov/forms/. The filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers refer to http://www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 19-21, 23-24, and 26-30 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-5, 12-15 and 17 of U.S. Patent No. 10,821,130 (‘130) in view of Smith et al (PLoS One, 2010, 5(9), 1-10; of record) and further in view of in view of Petrus (US 8,486,889; of record).
Although the claims at issue are not identical, they are not patentably distinct from each other because:
Instant Claim 19 is drawn to a method for reducing or preventing cognitive decline in an elderly subject comprising administering 0.13mg/day to 130mg/day of vitamin B6. Dependent claims 20-21, 23-24 and 26-30 recite limitations drawn to elderly human subject, oral administration, administration of a nitric oxide releasing compound which can be citrulline, administration of vitamin B9 and/or vitamin B12 with vitamin B6, and dosage of vitamin B9 and vitamin B12.
Claims 1, 13 and 14 of ‘130 are drawn to a method of attenuating, treating, reducing risk of and/or reducing severity of cognitive aging in a non-demented individual comprising administering a composition comprising an effective amount of an omega-3 acid, a nitric oxide releasing compound comprising citrulline, and vitamin B12 wherein the daily dose provide 50 to 100 times the recommended daily dose of vitamin B12 per day and wherein the composition further comprises one or more additional vitamins selected from a Markush group which includes vitamin B6 and vitamin B9. Dependent claims 2-5, 12 and 15-17 of ‘130 recite limitations drawn to amount of vitamin B12 in terms of recommended daily allowance, subject being an older human adult, administration daily for a month, the individual having a genotype indicating risk of cognitive decline.
The claims of ‘130 differ from the instant claims in that the instant claims administer vitamin B6, a nitric oxide releasing compound as active agents, and also include vitamin B9 and vitamin B12 as additional active agents, whereas ‘130 includes omega-3 fatty acid as an active agent. However, it would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to modify the method of ‘130 in view of Smith et al, and Petrus whose teachings are set forth above, to arrive at the claimed method.
In the instant case ‘130 teaches the method applicant claims including the vitamins used as active agents. Although the claims of ‘130 use an omega-3 fatty acid as an active agent, one of ordinary skill in the art would readily recognize that the scheme taught by ‘130 could be modified in view of Smith et al and Petrus to arrive at the claimed method with a reasonable expectation of success. The use of known members of classes of active agents in methods of treatment taught in the prior art is not seen to render the instantly claimed method unobvious over the art. Once the general scheme has been shown to be old, the burden is on the applicant to present reason or authority for believing that exclusion of the omega-3 fatty acid would alter the nature of the product and thus the unobviousness of the method of using the claimed vitamins and nitic oxide releasing compound like citrulline as the active agents especially in view of Smith et al and Petrus.
Response to Applicant’s Remarks
Regarding the rejection of claims 19-28 on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-5, 12-15 and 17 of U.S. Patent No. 10,821,130 (‘130) in view of Smith et al (PLoS One, 2010, 5(9), 1-10; of record) applicant has requested that the double patenting rejection be withdrawn or held in abeyance until claims are otherwise allowable in the present application.
Applicant also submits that claims 29-30 are patentable over the cited art for at least substantially the same reasons discussed above for independent claim 19 form which these newly submitted claims depend.
Regarding the double patenting rejection(s) of record applicant has requested that they be held in abeyance until allowable subject matter is indicated. The filing of a terminal disclaimer, or filing a showing that the claims subject to the rejection are patentably distinct from the reference application’s/patents claims is necessary. Since neither has been made of record the rejection(s) are being maintained.
The double patenting rejection as set forth above is made of record in view of the amendment to claim 19. Amended claim 19 and dependents thereof are still rejectable.
Conclusion
1. Pending claims 19-21, 23-24, and 26-30 are rejected.
2. Claims 1-18, 22 and 25 have been canceled.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GANAPATHY KRISHNAN whose telephone number is (571)272-0654. The examiner can normally be reached M-F 8.30am-5pm.
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/GANAPATHY KRISHNAN/Primary Examiner, Art Unit 1693
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