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 .
Claims 19-28 are pending in the application. Claims 1-18 have been canceled. Preliminary amendment filed 10/10/2023.
Priority
This application is a divisional of 16603749 filed 10/08/2019, now abandoned, which is a 371 of PCT/EP2017/082148 filed 12/11/2017 which claims the benefit of 62580574 filed 11/02/2017, the benefit of 62484156 filed 04/11/2017, and the benefit of 62484119 filed 04/11/2017. This application claims foreign priority to EPO EP17193916.8 filed 09/29/2017, under 35 U.S.C. 119(a)-(d). The certified copy of the priority document has been filed in the parent application 16/603,749.
The parent application EPO EP17193916.8 to which priority is claimed is seen to provide adequate support under 35 U.S.C. 112 for claims 19-28 of this application.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
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.
Claims 19-28 are rejected under 35 U.S.C. 112(a), because the specification, while being enabling for reducing cognitive decline in an elderly subject via administration of Vitamin B6, does not reasonably provide enablement for preventing cognitive decline. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
Applicant have reasonably disclosed that the claimed composition is useful as a therapeutic agent for reducing cognitive decline in elderly people. However, the claims also encompass using the claimed composition to prevent cognitive decline. The term "prevent" means to stop from occurring and, thus, requires a higher standard for enablement than does "treat", especially since it is well accepted in the medical art that the majority of cognitive impairment cannot be always totally prevented with current methods. Therefore, to practice the claimed invention herein, a person of skill in the art would have to engage in undue experimentation to test how the instant composition prevents cognitive decline in an elderly subject with no assurance of success.
Genetech, 108 F.3d at 1366 states that “a patent is not a hunting license. It is not a reward for search, but compensation for its successful conclusion” and “patent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable.” (Genentech, Inc. v. Novo Nordisk, A/S, 108 F.3d 1361, 1365, 42 USPQ2d 1001, 1004 (Fed. Cir. 1997)). In In re ‘318 Patent Infringement Litigation, 92 USPQ2d 1385 (Fed. Cir. 2009) at 1391, 1392 the court stated, “Thus, at the end of the day, the specification, even read in light of the knowledge of those skilled in the art, does no more than state a hypothesis and propose testing to determine the accuracy of that hypothesis. That is not sufficient. See Rasmusson V. SmithKline Beecham Corp., 413 F.3d 1318, 1325 (Fed. Cir. 2005) (“If mere plausibility were the test for enablement under section 112, applicants could obtain patent rights to “inventions” consisting of little more than respectable guesses as to the likelihood of their success. When one of the guesses later proved true, the “inventor” would be rewarded the spoils instead of the party who demonstrated that the method actually worked. That scenario is not consistent with the statutory requirement that the inventor enable an invention rather than merely proposing an unproved hypothesis.”).
Dependent claims are also rejected due to non-enablement of base claim 19.
In light of the foregoing, the enablement requirement for “prevention” in claim 19 is not satisfied.
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) 19-21 and 25-27 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Smith et al (PLoS One, 2010, 5(9), 1-10).
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; dosage of vitamin B9 as in claim 27). The elderly subjects were given tablets containing the active agents (page 2, right col. third full para; oral administration as in claim 21).
Therefore, Smith et al anticipates claims 19-21 and 25-27.
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) 22-24 and 28 are rejected under 35 U.S.C. 103 as being unpatentable over Smith et al (PLoS One, 2010, 5(9), 1-10) in view of Petrus (US 8,486,889).
The teachings of Smith et al are set forth above. 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 administration of a nitric oxide releasing compound as in claims 22-24.
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; as in claims 22-24). Citrulline is suggested as a component with vitamin B6 and B12 in oral tablets to prevent endothelial dysfunction associated with cognitive decline.
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.
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 to obtain maximum beneficial effects.
Claims 19-21 and 26-28 are rejected 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).
Miller teaches dietary supplement containing vitamins which promotes 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 and 26). The composition comprising the vitamins can be administered to humans (para 0033). Even though the method for reducing or preventing 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.
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.
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.
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, 25 and 27-28.
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.
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 in a method of reducing or preventing cognitive decline in an elderly subject 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.
Claim(s) 22-24 are rejected 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).
The teachings of Miller, Hendricks and Smith are set forth above. Miller, Hendricks and Smith do not disclose administering a nitric oxide releasing compound like citrulline and its dosage as in claims 22-24.
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; as in claims 22-24). Citrulline is suggested as a component with vitamin B6 and B12 in oral tablets to prevent endothelial dysfunction associated with cognitive decline.
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.
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 to obtain maximum beneficial effects.
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 19-28 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).
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 20-28 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 alone as the active agent and includes 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, 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 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.
Conclusion
1. Pending claims 19-28 are rejected.
2. Claims 1-18 have been canceled.
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/GANAPATHY KRISHNAN/Primary Examiner, Art Unit 1693