DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.1
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on Jan 8 2026 has been entered.
Status of the Claims
Claims 1, 2, 4, 5, 8, 10-12 and 15-19 is/are pending in this application.
Response to Arguments
Applicant's arguments filed Jan 8 2026, with respect to the rejection(s) of Claims 1-5, 8, 10-12 and 15-19 rejected under 35 U.S.C. 103(a) as being unpatentable over (Clark ‘171 publication) in view of Clarke, or the '766 publication), have been fully considered but they are not persuasive. See below rejection and response to Attorney arguments.
The Attorney response of Jan. 8, 2026 states Application No.14/453,999 has been abandoned. The rejection of claims 1,4, 5, 8, 10-12 and 15-19, based on this abandoned conflict application have been withdrawn.
Applicant's arguments filed Jan. 8, 2026 have been fully considered but they are not persuasive. The ODP rejection of claims 1, 4, 5, 8, 10-12 and 15-19 over claims 1-10 and 13-18 of US Patent No. 10,660,958 ("the '958 patent") in view of the '171 publication is maintained. Further, the ODP rejection of claims 1, 4, 5, 8, 10-12 and 15-19 over claims 1-5 of US Patent 8,642,654 ("the '654 patent") in view of the '171 publication and the '766 publication is maintained.
Claim Rejections - 35 USC § 103(a)
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1-5, 8, 10-12 and 15-19 are rejected under 35 U.S.C. 103(a) as being unpatentable over WO2011/101171 A1 (Clark et al., the ‘171 publication), previously cited by the Examiner, in view of WO 2010/021766 (Clarke, or the '766 publication), published Feb 25, 2010, cited by applicant on IDS
Claim 1 is directed to a method of maintaining or improving the muscle power output of a healthy subject having a high level of fitness in need thereof during exercise comprising administering to the subject a monoester of (R)-3-hydroxybutyrate formed between the hydroxybutyrate and an alcohol selected from R-1,3-butanediol or glycerol at a dose level of at least 300 mg/kg of the subject's weight to provide a blood plasma ketone level of 1 to 20 mM.
Similar to claim 1, claim 10 is directed to a method of maintaining or improving the muscle power output of a healthy subject having a high level of fitness in need thereof during exercise comprising administering to the subject a composition comprising a monoester of (R)-3-hydroxybutyrate formed between the hydroxybutyrate and an alcohol selected from R-1,3-butanediol or glycerol at a dose level of at least 300 mg/kg of the subject's weight to provide a blood plasma ketone level of 1 to 20 mM.
While the invention’s specification does not necessarily recite the terms of “in need thereof,” it defines the claimed subject in need as a healthy subject having a high level of fitness as athletes and military personnel at page 2, fourth paragraph, where ingestion of the claimed compound/composition can occur immediately before or during exercise to maintain or improve muscle power delivery, see page 5, 3rd paragraph.
The claims are construed as the administration of claimed monoester of (R)-3-hydroxybutyrate, (taught by the ‘171 publication) to healthy subjects in need (with high levels of fitness, such as military and athletes per the ‘766 publication) thereof so as to maintain and improve muscle power output of said subject, at the claimed doses.
Regarding claims 1 and 10, the ‘171 publication teaches the treatment of a healthy subject as per Example 7, where human subjects were administered D-β-hydroxybutyrate-R 1,3-butanediol monoester, see page 20, lines 4-9. The ‘171 publication discloses the elected species, 3-hydroxybutyl 3-hydroxybutyrate as ketone (UorR) or D-β-hydroxybutyrate-R 1,3butanedio monoester in Examples 1-6/Tables 1-6 (on pages 15-20) and Example 7 (on page 20). The ‘171 publication discloses this ketone body or ketone body include a hydroxybutyrate ester, see abstract and claim 1.
With regard to claim 10, the ‘171 publication teaches the use of a composition (ingestible) for the claimed method, see examples 1-10 on pages 14-22; claims 1-34.
As required by claims 1 and 10, the ‘171 publication teaches the claimed doses (at least 300 mg/kg) where the subject user ingests at least 300 mg of the claimed ketones per kg of body weight per day, see page 3, lines 12-14.
Regarding claims 1 and 10 wherein the blood plasma ketone level is from 1 to 20 mM, the ‘171 publication teaches that preferred amounts of hydroxybutyrate ester or partial ester in the subject are blood plasma ketone levels of at least 0.1 mM, preferably at least 0.2 mM, more preferably at least 1 mM and optimally at least 3 mM, see page 3, lines 6-7.
Claims 1 and 10 note the limitation of maintaining or improving muscle power output “during exercise.” The ‘171 publication teaches that its compounds and compositions are consumed by a user prior to anticipated fatigue, see page 3, 4th paragraph. See also page 14, first and second paragraphs. Thus, consumption of the same compounds taught by the ‘171 publication and claimed by the invention, will have the effect of maintaining or improving muscle power out “during exercise.”
Accordingly, because the ‘171 publication teaches the administration of the same compound to the same healthy subject population at the same claimed doses of 100 mg/kg, claims 1 and 10 are obvious.
While the ‘171 publication discloses the same method of administering the same ketone bodies at the same doses, it does not necessarily recite the limitation of the healthy subject having a high level of fitness. However, a person having ordinary skill in the art (PHOSITA) would find it prima facie obvious to treat healthy subjects with a high level of fitness (such as athletes or military subjects known in the art as per the ‘766 publication) with the doses of ketone bodies of the ‘171 publication as elaborated below.
For example, the '766 publication teaches the use of the compound for the claimed method (see claims 1, 4 and 7), and in particular, for a healthy subject, with a high level of fitness) as claimed by applicant, see page 2, lines 25-28; page 6, lines 11-27 (e.g., military members, athletes, body builders, etc.); page 7, lines 31-32.
See Table below for summary of obviousness analysis of claims 1 and 10 over the ‘171 publication in view of the ‘766 publication.
Claims 1 and 10: A method of maintaining or improving the muscle power output of a healthy subject having a high level of fitness (as athletes and military personnel at page 2, fourth paragraph of the specification)
Regarding claims 1 and 10, the ‘171 publication teaches the treatment of a healthy subject as per Example 7, where human subjects were administered D-β-hydroxybutyrate-R 1,3-butanediol monoester, see page 20, lines 4-9. With regard to the limitations of subjects of high levels of fitness, see the teachings of the ‘766 publication where such military and athletic subjects would undergo such levels of exercise, see below for further detail.
exercise comprising administering to the subject a monoester of (R)-3-hydroxybutyrate formed between the hydroxybutyrate and an alcohol selected from R-1,3-butanediol or glycerol, including compositions as per claim 10
the ‘171 publication teaches the treatment of a healthy subject as per Example 7, where human subjects were administered D-β-hydroxybutyrate-R 1,3-butanediol monoester, see page 20, lines 4-9. The ‘171 publication discloses the elected species, 3-hydroxybutyl 3-hydroxybutyrate as ketone (UorR) or D-β-hydroxybutyrate-R 1,3butanedio monoester in Examples 1-6/Tables 1-6 (on pages 15-20) and Example 7 (on page 20), including compositions thereof, see ‘171 publication, see examples 1-10 on pages 14-22; claims 1-34.
at a dose level of at least 300 mg/kg of the subject's weight
the ‘171 publication teaches the claimed doses (at least 300 mg/kg) where the subject user ingests at least 300 mg of the claimed ketones per kg of body weight per day, see page 3, lines 12-14
to provide a blood plasma ketone level of 1 to 20 mM.
the ‘171 publication teaches that preferred amounts of hydroxybutyrate ester or partial ester in the subject are blood plasma ketone levels of at least 0.1 mM, preferably at least 0.2 mM, more preferably at least 1 mM and optimally at least 3 mM, see page 3, lines 6-7.
a healthy subject having a high level of fitness during exercise, note a healthy subject having a high level of fitness as athletes and military personnel at page 2, fourth paragraph
the '766 publication teaches the use of the compound for the claimed method (see claims 1, 4 and 7), and in particular, for a healthy subject, with a high level of fitness) as claimed by applicant, see page 2, lines 25-28; page 6, lines 11-27 (e.g., military members, athletes, body builders, etc.); page 7, lines 31-32. One of ordinary skill in the art would have a reasonable expectation of success in administering the claimed ketone body compounds while the athletic subjects undergo vigorous and prolonged exercise
With regard to claim 2 wherein the muscle power output is skeletal muscle power output, the ‘171 publication teaches the use of the taught ketone body (as elected by applicant), that ketone bodies are known to reduce skeletal muscle impairment or fatigue, see page 1, line 26-27.
With regard to claims 4 and 5 and the limitations of improved power output of at least 0.25% relative to a placebo, or is at least 1 Watt relative to a placebo when measured in a controlled test over 30 minute, while the ‘171 publication does not teach the particular increases in power output spelled out, because the claimed invention and the '766 publication use the same ketone body, in the same subjects, such properties as claimed by claims 4 and 5 are deemed necessarily present in the method taught by the ‘171 publication. 2
Regarding claim 8 wherein the circulating levels of hydroxybutyrate and acetoacetate in the blood of the subject are from 1 to 5 mM, the ‘171 publication teaches that preferred amounts of hydroxybutyrate ester or partial ester in the subject are blood plasma ketone levels of at least 0.1 mM, preferably at least 0.2 mM, more preferably at least 1 mM and optimally at least 3 mM, see page 3, lines 6-7.
Regarding claim 11 wherein the composition comprises water and a monoester of (R)-3-hydroxybutyrate formed between the hydroxybutyrate and an alcohol selected from R-1,3-butanediol or glycerol, the ‘171 publication teaches compositions are diluted with a suitable liquid, for example water, fruit juice or milk, preferably at a ratio of 1: 1 to 1: 10, more preferably 1 :3 to 1 :7 of dry composition to liquid, see page 4, lines 13-15.
Regarding claim 12 wherein the monoester of (R)-3-hydroxybutyrate formed between the hydroxybutyrate and an alcohol selected from R-1,3-butanediol or glycerol comprises (R)-3-hydroxybutyrate-R-1,3-butanediol monoester, the ‘171 publication teaches a ketone body ester (monoester), see page 5, line 11 as well as multiple other references throughout the '171 publication. With regard to claim 15 wherein the composition further comprises one or more selected from the group consisting of a flavoring, a protein, a carbohydrate, a sugar, a fat, a fiber, a vitamin, and a mineral, the ‘766 publication teaches the use of flavorings, carbohydrate, fat, sugars, vitamins and minerals see protein see page 9, line 20 to page 10, line 2.
With regard to claims 16-17, directed to , wherein the administration occurs before exercise, the ‘171 publication teaches that its compounds and compositions are consumed by a user prior to anticipated fatigue, see page 3, 4th paragraph. See also page 14, first and second paragraphs. While not expressly reciting the limitation of administration prior to exercise, claims 16-17 are obvious, as the ‘171 publication teaches administration prior to a fatiguing situation, as exercise is known to be.
The rationale to do so is the teaching of administration of these compounds and compositions claimed by applicant and taught by the ‘171 publication that would have led one of ordinary skill in the art to modify the ‘171 publication (administration before exercise as a fatiguing situation) to arrive at the claimed invention.
With regard new claims 18-19 and the limitations wherein the exercise is carried out over more than 20 minutes and the monoester is delivered in 2 or more doses, ‘171 publication teaches an overlapping amount of doses where it notes administration of a composition require of one or more doses of the composition, preferably at least 2 doses, more preferably 2 to 8, for example 3 or 6 doses consumed daily. See page 3, lines 19-25.
With regard to the limitation of exercise carried for over 20 minutes, while this particular time period is not expressly recited in the ‘171 publication, the ‘766 publication teaches the ‘171 publication (see page 1, second paragraph) notes the ingestion of ketone bodies can lead to clinical benefits such as enhancement of physical performance. Further, the ‘171 publication notes the composition prevents, alleviates or treats fatigue, and is especially advantageous for use in military applications. See page 14, lines 11-14. A PHOSITA would routinely optimize using the taught monoester of (R)-3-hydroxybutyrates in military applications, where the PHOSITA would readily envisage military applications taking place in periods for over 20 minutes, especially as the ‘766 publication discloses administration to healthy subjects such as athletes and military members, known to have a high level of fitness. See page 7, lines 31-32.
RESPONSE TO ATTORNEY ARGUMENTS:
With regard to the ‘171 publication, the Attorney response states claims 1 and 10 specify a method of maintaining or improving the muscle power output of a healthy subject having a high level of fitness in need thereof during exercise, in contrast, the '171 publication discloses delivering in sufficient amounts, a ketone body and masking their bitter/unpalatable taste (i.e., negative organoleptic properties) with no concern or distinction between healthy or not healthy populations, with a lack of benefit afforded a particular subject population. See statements on pages 4-5 of the Attorney response.
The Attorney response states the '171 publication does not teach a PHOSITA to improve or maintain muscle power output in any subject at all (as claimed), let alone how to maintain or improve the muscle power output of a healthy person engaged in exercise. See bottom of page 4 of response.
The Attorney response states the '171 publication does not suggest the claimed monoester of (R)-3- hydroxybutyrate provides the unexpected and unknown improvement in muscle power output demonstrated by Applicant nor that such improvement happens in an exercising, healthy subject by ingestion of the ester prior to or during exercise. See response top of page 5.
In rebutting the Examiner, the Attorney response states the ‘766 Publication does not remedy any deficiencies of the ‘171 publication (administering the compositions to a healthy subject with a high level fitness). The Attorney response states "healthy" as per the ‘766 Publication concerns the weight of the subject, not a high level of fitness or a subject’s exercise as claimed. See page 5 of the response.
The Attorney response states the ‘766 Publication’s reference to a "healthy" subject is with suppressing appetite, promoting weight loss, treating obesity, maintaining healthy weight, or decreasing the ratio of fat to lean muscle (fat reduction generally) where “Health" is described as "healthy" or "non-healthy'' weight. Id. The Attorney response states there is not a suggestion here, or elsewhere in the ‘reference the taught compounds improve or maintain muscle power output of a healthy, highly fit subject. Id.
The Attorney response states the ‘766 publication’s reference to a "healthy" subject by the Examiner, is that compound may be used to treat muscle impairment or fatigue, conditions unrelated to the claimed maintenance or improvement of improving intrinsic power output of a muscle engaged in exercise, and therefore the reference cannot teach or suggest its quantitative increase. Id.
In response to the Attorney arguments, per MPEP 2145, citing to MPEP 706(I.)3, in considering Rebuttal arguments by Applicant, the Examiner notes the burden of proof for claim patentability rejections is a “preponderance of evidence” test, that is, it is more likely than not the claim is unpatentable in view of the prior art and evidence of record.
The evidence of record detailed above in the maintained rejection notes the ‘171 publication teaches the treatment of a healthy subject as per Example 7, where human subjects were administered D-β-hydroxybutyrate-R 1,3-butanediol monoester at overlapping doses, with overlapping blood plasma ketone levels, where the subject/user consumes the claimed compounds prior to anticipated fatigue.
While Applicant argues the purpose of the ‘171 publication is not equivalent to the intended use of the claimed invention, absent a true teaching away by the ‘171 publication, the preponderance of evidence on record indicates the administration of the monoester to healthy subjects, as there is not a teaching away despite the Attorney arguments detailed above.
With regard to the deficiency of the ‘171 publication as remedied by the ‘766 publication, a PHOSITA would find it prima facie obvious to treat healthy subjects with a high level of fitness (such as athletes, military member subjects known in the art as per the ‘766 publication) with the doses of ketone bodies of the ‘171 publication as elaborated below. The preponderance of evidence on record indicates the administration of the claimed compound to the claimed subject as detailed in the above obviousness rejection.
With regard to the Examiner’s rebuttal of the alleged hindsight reconstruction, the Attorney response states because neither the '171 publication nor the '766 publication teach that the monoester compounds improve or maintain power output levels of muscle, the Examiner’s citation of the prior art is impermissible hindsight and ex post facto analysis.
In response, the examiner notes the same drug is administered to the claimed patient population in amounts consistent with those taught by applicant's specification. With regard to the claimed subject in need, a broad and reasonable interpretation of such is that all human subjects are in need of maintaining or improving the muscle power output of a healthy subject, such as a healthy human. See above rejection highlighting disclosure from Example 1 of the specification.
With regard to the limitation of the subject in need requiring a high level of fitness, the '766 publication teaches the use of the compound for the claimed method (see claims 1, 4 and 7), and in particular, for a healthy subject, with a high level of fitness) as claimed by applicant, see page 2, lines 25-28; page 6, lines 11-27 (e.g., military members, athletes, body builders, etc.); see page 7, lines 31-32. A PHOSITA would have a reasonable expectation of success in administering the claimed ketone body compounds while the athletic subjects, with a high level of fitness, undergo exercise, including periods of 20 minutes or more.
Reiterating the points made above, the evidence of record detailed above in the maintained rejection notes the ‘171 publication teaches the treatment of a healthy subject as per Example 7, where human subjects were administered D-β-hydroxybutyrate-R 1,3-butanediol monoester at overlapping doses, with overlapping blood plasma ketone levels, where the subject/user consumes the claimed compounds prior to anticipated fatigue.
While Applicant argues the purpose of the ‘171 publication is not equivalent to the claimed invention’s intended use, absent a true teaching away by the ‘171 publication, the preponderance of evidence on record indicates the administration of the monoester to healthy highly fit subjects, as there is not a teaching away despite the Attorney arguments detailed above.
With regard to the deficiency of the ‘171 publication as remedied by the ‘766 publication, a PHOSITA would find it prima facie obvious to treat healthy subjects with a high level of fitness (such as athletes, military member subjects known in the art as per the ‘766 publication) with the doses of ketone bodies of the ‘171 publication as elaborated below. The preponderance of evidence on record indicates the administration of the claimed compound to the claimed subject as detailed in the above obviousness rejection.
Non-Statutory Double Patenting Rejections
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 Web site contains terminal disclaimer forms which may be used. Please visit http://www.uspto.gov/forms/. The filing date of the application will determine what form 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.
NEW OBVIOUSNESS REJECTION:
Claims 1, 4, 5, 8, 10-12 and 15-17 are provisionally rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 3-7,
11-14, 16, and 18-21 of copending Application No.19384555.
This is a provisional obviousness-type double patenting rejection because the conflicting claims have not in fact been patented. The contents and disclosure of the rejected claims are discussed above and hereby incorporated herein.
Regarding claims 1 and 10 and the methods maintaining/improving muscle power output of a subject, the conflict application generally claims a method of improving endurance of a healthy subject during exercise or adding muscle recover after exercise by reducing glycogen loss and/or protein breakdown in the subject, comprising administering (before or during exercise) an ester of D-beta hydroxybutyrate (R-(3)-hydroxybutyrate as claimed, and optionally water), where the D-beta hydroxybutyrate ester is one of a non-fully esterified polyhydric alcohol (such as 1-3 butanediol). See conflict claims 20-21.
Regarding claims 1 and 10 and the limitation of a monoester of (R)-3-hydroxybutyrate formed between the hydroxybutyrate and an alcohol selected from R-1,3-butanediol or glycerol the conflict application’s claims 3-7 are directed to 1-3 butanediol or glycerol monoesters of D- hydroxybutyrate. See also conflict claims 11-14, 16 and 18-19 directed to a method reducing glycogen loss/protein breakdown in a subject in need during exercise.
Regarding claims 1 and 10, the conflict Application discloses one dose of a ketone body ester to provide a circulating level of hydroxybutyrate and acetoacetate in the blood from 1 to 10 mM, see conflict claim 13.
While not explicitly reciting the limitations of maintaining or improving the muscle power output of a healthy subject having a high level of fitness in need thereof during exercise, it would be obvious to treat such subjects where claims 20-21 are directed to a method improving endurance during exercise, where improvement or maintenance of muscle power output of healthy subject with a high level of fitness would be prima facie obvious to a PHOSITA where the conflict application teaches a method of improving endurance during exercise in a healthy subject.
With regard to claims 4 and 5 and the limitations of improved power output and wherein the increased power output of at least 0.25% relative to a placebo, or is at least 1 Watt relative to placebo in a controlled test of 30 minutes, while conflict Application does not teach the particular increases in power output spelled out, because the claimed invention and cited prior art use the same ketone body, in the same subjects, such properties as claimed by claims 4 and 5 are deemed inherent to the method taught by the conflict Application.
Regarding claim 8, the conflict Application discloses one dose of a ketone body ester to provide a circulating level of hydroxybutyrate and acetoacetate in the blood from 1 to 10 mM, see conflict claim 13.
Regarding the water and monoester limitations of claims 11-12, the conflict Application discloses the ketone body or ketone body ester comprises (R)-3-hydroxybutyl-(R)-3-hydroxybutyrate, see conflict claim 21.
Regarding claim 15 and the limitation of further comprising a fat, the conflict Application discloses the composition further comprises a mid-chain triglyceride, with formula CH2(R1)-CH2(R2)-CH2(R3), wherein R1, R2 and R3 are fatty acids having 5 to 12, see conflict claims 18-19.
Regarding claims 16-17 and the limitation of administration before exercise, the conflict Application discloses administration before or during exercise, see conflict claims 20-21.
Claims 1, 4, 5, 8, 10-12 and 15-19 are provisionally rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-19 of copending Application No. 19384555, in view of the WO2011101171A1, the ‘171 publication.
This is a provisional obviousness-type double patenting rejection because the conflicting claims have not in fact been patented. The contents and disclosure of the rejected claims are discussed above and hereby incorporated herein.
While the conflict applications claims disclose the subject matter of claims 1, 4, 5, 8, 10-12 and 15-17 as detailed above, they do not necessarily teach the particular species of claims 18-19 as detailed below. However a PHOSITA would find it prima facie obvious to combine the method of the conflict application with the teachings of the ‘171 publication, as to arrive at a method of administration to a subject under exercise for over 20 minutes and the ketone monoester administered in 2 or more doses.
With regard new claims 18-19 and the limitations of exercise carried for over 20 minutes and the monoester is delivered in 2 or more doses, ‘171 publication teaches an overlapping amount of doses where it notes administration of a composition require of one or more doses of the composition, preferably at least 2 doses, more preferably 2 to 8, for example 3 or 6 doses consumed daily. See page 3, lines 19-25.
With regard to the limitation of exercise carried for over 20 minutes, while this particular time period is not expressly recited in the ‘171 publication, the ‘766 publication teaches the ‘171 publication (see page 1, second paragraph) notes the ingestion of ketone bodies can lead to clinical benefits such as enhancement of physical performance. Further, the ‘171 publication notes the composition prevents, alleviates or treats fatigue, and is especially advantageous for use in military applications. See page 14, lines 11-14. A PHOSITA would routinely optimize using the taught monoester of (R)-3-hydroxybutyrates in military applications, where the PHOSITA would readily envisage military applications taking place in periods for over 20 minutes, especially as the ‘766 publication discloses administration to healthy subjects such as athletes and military members, known to have a high level of fitness. See page 7, lines 31-32.
MAINTAINED REJECTIONS:
Claims 1, 4, 5, 8, 10-12 and 15-19 remain rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-10 and 13-18 of U.S. Patent 10,660,958 in view of WO 2011/101171 A1 (Clark et al., the ‘171 publication), previously cited by the Examiner and WO 2010/021766 (Clarke, or the '766 publication), published Feb 25, 2010, cited by applicant on IDS. The contents and disclosure of the rejected claims are discussed above and hereby incorporated herein.
U.S. Patent 10,660,958 generally claims a method of improving the organoleptic properties of 3-hydroxybutyl-(R)-3-hydroxybutyrate, wherein the method consists of adding a bitter flavoring to the 3-hydroxybutyl-(R)-3-hydroxybutyrate (claim 1), where claim 9 is directed to a method of treatment of muscle impairment, or muscle fatigue consisting of administering a composition according to claim 1 to a subject in need thereof, see claims 1 and 9.
While there is no recitation of the treatment of a healthy subject with high fitness per se in the claims, it would be obvious to treat such a healthy subject, as such subject would be in need for the treatment of muscle impairment or muscle fatigue as per claim 9, etc. Further, all healthy subjects, even those with high levels of fitness, would be in need of maintaining or improving muscle output. The cited art teaches the ingestion of the same compounds prior to the start of exercise (as per pending claim 17), and therefore, these compounds will increase or maintain muscle power output during exercise.
Further, while silent with regard in the claims with regard to a subject with high fitness, the claimed method’s subject is obvious over the ‘958 patent as follows.
Regarding claims 1 and 10, the ‘171 publication teaches the treatment of a healthy subject as per Example 7, where normal human subjects were administered D-β-hydroxybutyrate-R 1,3 butanediol monoester, see page 20, lines 4-9.
Regarding claims 1 and 10, the ‘171 publication discloses the elected species, 3-hydroxybutyl 3-hydroxybutyrate as ketone (UorR) or D-β-hydroxybutyrate-R 1,3butanedio monoester in Examples 1-6/Tables 1-6 (on pages 15-20) and Example 7 (on page 20).
Regarding claims 1 and 10, the ‘171 publication discloses this ketone body or ketone body include a hydroxybutyrate ester, see abstract and claim 1.
With regard to claim 10, the ‘171 publication teaches the use of a composition (ingestible) for the claimed method, see examples 1-10 on pages 14-22; claims 1-34.
As required by claims 1 and 10, the ‘171 publication teaches the claimed doses (at least 300 mg/kg) where the subject user ingests at least 300 mg of the claimed ketones per kg of body weight per day, see page 3, lines 12-14.
Regarding claims 1 and 10 wherein the blood plasma ketone level is from 1 to 20 mM, the ‘171 publication teaches that preferred amounts of hydroxybutyrate ester or partial ester in the subject are blood plasma ketone levels of at least 0.1 mM, preferably at least 0.2 mM, more preferably at least 1 mM and optimally at least 3 mM, see page 3, lines 6-7.
Claims 1 and 10 note the limitation of maintaining or improving muscle power output “during exercise.” The ‘171 publication teaches that its compounds and compositions are consumed by a user prior to anticipated fatigue, see page 3, 4th paragraph. See also page 14, first and second paragraphs. Thus, consumption of the same compounds taught by the ‘171 publication and claimed by the invention, will have the effect of maintaining or improving muscle power out “during exercise.”
Accordingly, because the ‘171 publication teaches the administration of the same compound to the same healthy subject population at the same claimed doses of 100 mg/kg, claims 1 and 10 are obvious.
While the ‘171 publication discloses the same method of administering the same ketone bodies at the same doses with respect to prolonged and vigorous exercise, it does not necessarily recite the limitation of the healthy subject having a high level of fitness. However, it would be obvious to do so to a PHOSITA with a reasonable expectation of success based on the teachings of prior art. As noted above, said vigorous and prolonged exercise is indefinite. However, treated healthy subjects in need, in particular those of a high level of fitness as taught by the cited prior art, will be obvious to administer the claimed compounds and compositions as claimed.
For example, the '766 publication teaches the use of the compound for the claimed method (see claims 1, 4 and 7), and in particular, for a healthy subject, with a high level of fitness) as claimed by applicant, see page 2, lines 25-28; page 6, lines 11-27 (e.g., military members, athletes, body builders, etc.); page 7, lines 31-32.
With regard to claims 4 and 5 and the limitations of improved power output and wherein the increased power output of at least 0.25% relative to a placebo, or is at least 1 Watt relative to placebo in a controlled test of 30 minutes, while the ‘958 patent and the ‘171 publication do not teach the particular increases in power output spelled out, because the claimed invention and cited prior art use the same ketone body, in the same subjects, such properties as claimed by claims 4 and 5 are deemed inherent to the method taught by the ‘171 publication.
Regarding claim 8 wherein the circulating levels of hydroxybutyrate and acetoacetate in the blood of the subject are from 1 to 5 mM, the ‘171 publication teaches that preferred amounts of hydroxybutyrate ester or partial ester in the subject are blood plasma ketone levels of at least 0.1 mM, preferably at least 0.2 mM, more preferably at least 1 mM and optimally at least 3 mM, see page 3, lines 6-7.
Regarding claim 11 wherein the composition comprises water and a monoester of (R)-3-hydroxybutyrate formed between the hydroxybutyrate and an alcohol selected from R-1,3-butanediol or glycerol, the ‘171 publication teaches compositions are diluted with a suitable liquid, for example water, fruit juice or milk, preferably at a ratio of 1: 1 to 1: 10, more preferably 1 :3 to 1 :7 of dry composition to liquid, see page 4, lines 13-15.
Regarding claim 12 wherein the monoester of (R)-3-hydroxybutyrate formed between the hydroxybutyrate and an alcohol selected from R-1,3-butanediol or glycerol comprises (R)-3-hydroxybutyrate-R-1,3-butanediol monoester, the ‘171 publication teaches a ketone body ester (monoester), see page 5, line 11 as well as multiple other references throughout the '171 publication.
With regard to claim 15 wherein the composition further comprises one or more selected from the group consisting of a flavoring, a protein, a carbohydrate, a sugar, a fat, a fiber, a vitamin, and a mineral, the ‘766 publication teaches the use of flavorings, carbohydrate, fat, sugars, vitamins and minerals see protein see page 9, line 20 to page 10, line 2.
With regard to claims 16-17, directed to the administration of the claimed compounds and compositions prior to exercise, the ‘171 publication teaches that its compounds and compositions are consumed by a user prior to anticipated fatigue, see page 3, 4th paragraph. See also page 14, first and second paragraphs. While not expressly reciting the limitation of administration prior to exercise, claims 16-17 are obvious, as the ‘171 publication teaches administration prior to a fatiguing situation, as exercise is known to be. Therefore, it would be obvious to ingest these compounds and compositions prior to exercise to treat muscle fatigue as per U.S. Patent 10,660,958.
With regard new claims 18-19 and the limitations of exercise carried for over 20 minutes and the monoester is delivered in 2 or more doses, ‘171 publication teaches an overlapping amount of doses where it notes administration of a composition require of one or more doses of the composition, preferably at least 2 doses, more preferably 2 to 8, for example 3 or 6 doses consumed daily. See page 3, lines 19-25.
With regard to the limitation of exercise carried for over 20 minutes, while this particular time period is not expressly recited in the ‘171 publication, the ‘766 publication teaches the ‘171 publication (see page 1, second paragraph) notes the ingestion of ketone bodies can lead to clinical benefits such as enhancement of physical performance. Further, the ‘171 publication notes the composition prevents, alleviates or treats fatigue, and is especially advantageous for use in military applications. See page 14, lines 11-14. A PHOSITA would routinely optimize using the taught monoester of (R)-3-hydroxybutyrates in military applications, where the PHOSITA would readily envisage military applications taking place in periods for over 20 minutes, especially as the ‘766 publication (See page 7, lines 31-32) discloses administration to healthy subjects such as athletes and military members, known to have a high level of fitness. MPEP 2144.05(II).
Claims 1, 4, 5, 8, 10-12 and 15-19 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-5 of U.S. Patent 8,642,654 B2 in view of WO 2011/101171 A1 (Clark et al., the ‘171 publication), previously cited by the Examiner and WO 2010/021766 (Clarke, or the '766 publication), published Feb 25, 2010, cited by applicant on IDS. The contents and disclosure of the rejected claims are discussed above and hereby incorporated herein.
U.S. Patent 8,642,654 B2 generally claims an ingestible composition comprising a compound which is 3-hydroxybutyl 3-hydroxybutyrate enantiomerically enriched with respect to (3R)-hydroxybutyl (3R)-hydroxybutyrate of formula (I):
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and a dietetically or pharmaceutically acceptable carrier and so forth, with overlapping, if not identical scope. Claim 4 recites the need to maintain a healthy weight, thus making it obvious to treat an otherwise healthy subject in need of some weight loss. Claim 5 notes the need to ingest these compounds and compositions prior to fatigue. Further, all healthy subjects would be in need of maintaining or improving muscle output. The cited art teaches the ingestion of the same compounds prior to the start of exercise, and therefore, these compounds will increase or maintain muscle power output during exercise.
While silent with regard in the claims with regard to a subject with high fitness, the claimed method is obvious over the 958 patent as follows.
Regarding claims 1 and 10, the ‘171 publication teaches the treatment of a healthy subject as per Example 7, where normal human subjects were administered D-β-hydroxybutyrate-R 1,3butanedio monoester, see page 20, lines 4-9.
Regarding claims 1 and 10, the ‘171 publication discloses the elected species, 3-hydroxybutyl 3-hydroxybutyrate as ketone (UorR) or D-β-hydroxybutyrate-R 1,3butanedio monoester in Examples 1-6/Tables 1-6 (on pages 15-20) and Example 7 (on page 20).
Regarding claims 1 and 10, the ‘171 publication discloses this ketone body or ketone body include a hydroxybutyrate ester, see abstract and claim 1.
With regard to claim 10, the ‘171 publication teaches the use of a composition (ingestible) for the claimed method, see examples 1-10 on pages 14-22; claims 1-34.
As required by claims 1 and 10, the ‘171 publication teaches the claimed doses (at least 300 mg/kg) where the subject user ingests at least 300 mg of the claimed ketones per kg of body weight per day, see page 3, lines 12-14.
Regarding claims 1 and 10 wherein the blood plasma ketone level is from 1 to 20 mM, the ‘171 publication teaches that preferred amounts of hydroxybutyrate ester or partial ester in the subject are blood plasma ketone levels of at least 0.1 mM, preferably at least 0.2 mM, more preferably at least 1 mM and optimally at least 3 mM, see page 3, lines 6-7.
Claims 1 and 10 note the limitation of maintaining or improving muscle power output “during exercise.” The ‘171 publication teaches that its compounds and compositions are consumed by a user prior to anticipated fatigue, see page 3, 4th paragraph. See also page 14, first and second paragraphs. Thus, consumption of the same compounds taught by the ‘171 publication and claimed by the invention, will have the effect of maintaining or improving muscle power out “during exercise.”
Accordingly, because the ‘171 publication teaches the administration of the same compound to the same healthy subject population at the same claimed doses of 100 mg/kg, claims 1 and 10 are obvious.
While the ‘171 publication discloses the same method of administering the same ketone bodies at the same doses with respect to prolonged and vigorous exercise, it does not necessarily recite the limitation of the healthy subject having a high level of fitness. However, it would have been prima facie obvious to do so to one of ordinary skill in the art with a reasonable expectation of success based on the teachings of prior art. However, treating healthy subjects in need, in particular those of a high level of fitness as taught by the cited prior art, would have been prima facie obvious.
For example, the '766 publication teaches the use of the compound for the claimed method (see claims 1, 4 and 7), and in particular, for a healthy subject, with a high level of fitness) as claimed by applicant, see page 2, lines 25-28; page 6, lines 11-27 (e.g., military members, athletes, body builders, etc.); page 7, lines 31-32.
With regard to claims 4 and 5 and the limitations of improved power output and wherein the increased power output of at least 0.25% relative to a placebo, or is at least 1 Watt relative to placebo in a controlled test of 30 minutes, while the ‘958 patent and the ‘171 publication do not teach the particular increases in power output spelled out, because the claimed invention and cited prior art use the same ketone body, in the same subjects, such properties as claimed by claims 4 and 5 are deemed inherent to the method taught by the ‘171 publication.
Regarding claim 8 wherein the circulating levels of hydroxybutyrate and acetoacetate in the blood of the subject are from 1 to 5 mM, the ‘171 publication teaches that preferred amounts of hydroxybutyrate ester or partial ester in the subject are blood plasma ketone levels of at least 0.1 mM, preferably at least 0.2 mM, more preferably at least 1 mM and optimally at least 3 mM, see page 3, lines 6-7.
Regarding claim 11 wherein the composition comprises water and a monoester of (R)-3-hydroxybutyrate formed between the hydroxybutyrate and an alcohol selected from R-1,3-butanediol or glycerol, the ‘171 publication teaches compositions are diluted with a suitable liquid, for example water, fruit juice or milk, preferably at a ratio of 1: 1 to 1: 10, more preferably 1 :3 to 1 :7 of dry composition to liquid, see page 4, lines 13-15.
Regarding claim 12 wherein the monoester of (R)-3-hydroxybutyrate formed between the hydroxybutyrate and an alcohol selected from R-1,3-butanediol or glycerol comprises (R)-3-hydroxybutyrate-R-1,3-butanediol monoester, the ‘171 publication teaches a ketone body ester (monoester), see page 5, line 11 as well as multiple other references throughout the '171 publication.
With regard to claim 15 wherein the composition further comprises one or more selected from the group consisting of a flavoring, a protein, a carbohydrate, a sugar, a fat, a fiber, a vitamin, and a mineral, the ‘766 publication teaches the use of flavorings, carbohydrate, fat, sugars, vitamins and minerals see protein see page 9, line 20 to page 10, line 2.
With regard to claims 16-17, directed to the administration of the claimed compounds and compositions prior to exercise, the ‘171 publication teaches that its compounds and compositions are consumed by a user prior to anticipated fatigue, see page 3, 4th paragraph. See also page 14, first and second paragraphs. While not expressly reciting the limitation of administration prior to exercise, claims 16-17 are obvious, as the ‘171 publication teaches administration prior to a fatiguing situation, as exercise is known to be.
With regard new claims 18-19 and the limitations of exercise carried for over 20 minutes and the monoester is delivered in 2 or more doses, ‘171 publication teaches an overlapping amount of doses where it notes administration of a composition require of one or more doses of the composition, preferably at least 2 doses, more preferably 2 to 8, for example 3 or 6 doses consumed daily. See page 3, lines 19-25.
With regard to the limitation of exercise carried for over 20 minutes, while this particular time period is not expressly recited in the ‘171 publication, the ‘766 publication teaches the ‘171 publication (see page 1, second paragraph) notes the ingestion of ketone bodies can lead to clinical benefits such as enhancement of physical performance. Further, the ‘171 publication notes the composition prevents, alleviates or treats fatigue, and is especially advantageous for use in military applications. See page 14, lines 11-14. A PHOSITA would routinely optimize using the taught monoester of (R)-3-hydroxybutyrates in military applications, where the PHOSITA would readily envisage military applications taking place in periods for over 20 minutes, especially as the ‘766 publication discloses administration to healthy subjects such as athletes and military members, known to have a high level of fitness. See page 7, lines 31-32.
Response to Attorney, re: US Patent No. 10.660.958 in view of the '171 Publication and ‘766 Publication The Attorney response states the test for obviousness -type double patenting analysis differs from that under 35U.S.C. § 103(a) in that "disclosure of the [reference] patent may not be used as prior art" (M.P.E.P. § 804). Instead, the "focus of any double patenting analysis necessarily is on the claims in the multiple patents or patent applications involved in the analysis" Id.
In response, it is noted that both the ‘171 publication and ‘766 publication teach the claimed subject, without reference to the reference disclosure.
The claims of the '958 patent specify a method of improving the organoleptic properties of 3-hydroxybutyl-(R)-3-hydroxybutyrate, wherein the method consists of adding a bitter flavoring to the 3-hydroxybutyl-(R)-3-hydroxybutyrate. The Examiner acknowledges that while there is no recitation of the treatment of a healthy subject with high fitness per se in the claims of the '958 patent, it would have been obvious to treat a healthy subject. The '958 patent is a 35 USC 371 filing of the '191 publication. The Attorney response states, for the reasons submitted supra, the '191 publication fails to teach or suggest administration of the claimed monoester to a healthy subject having a high level of fitness.
In response, it would be obvious to treat such a healthy subject, as such subject would be in need for the treatment of muscle impairment or muscle fatigue as per claim 9, etc., where the cited art teaches the ingestion of the same compounds prior to the start of exercise to increase or maintain muscle power during exercise.
While silent in the conflict claims with regard to a subject with high fitness, the claimed method is obvious over the ‘958 patent as follows.
The ‘171 publication teaches the treatment of a healthy subject as per Example 7, where normal human subjects were administered D-β-hydroxybutyrate-R 1,3 butanediol monoester, see page 20, lines 4-9.
The '766 publication teaches the use of the compound for the claimed method (see claims 1, 4 and 7), and in particular, for a healthy subject, with a high level of fitness) as claimed by applicant, see page 2, lines 25-28; page 6, lines 11-27 (e.g., military members, athletes, body builders, etc.); page 7, lines 31-32.
Response to Attorney re: US Patent 8,642.654 in view of the '171 Publication and the '766 Publication The Attorney response states for the same reasons submitted supra with respect to the '766 publication, a "healthy" subject in the context of suppressing appetite, treating obesity, promoting weight loss, maintaining a healthy weight or decreasing the ratio of fat to lean muscle is not the same as a healthy subject in the context of improving or maintaining the power output of muscles, especially where the subject is a healthy subject having a high level of fitness, as defined in the instant claims. Further, the Attorney response states as submitted supra, the treatment of muscle fatigue is entirely unrelated to the intrinsic power output of a muscle and maintaining or improving that characteristic.
In response, it would be obvious to treat such a healthy subject where the ‘654 patent teaches a composition for ingestion to maintain a healthy weight, where all healthy subjects would be in need of maintaining or improving muscle output.
While silent with regard in the claims with regard to a subject with high fitness, the claimed method is obvious over the ‘958 patent as follows.
The ‘171 publication teaches the treatment of a healthy subject as per Example 7, where normal human subjects were administered D-β-hydroxybutyrate-R 1,3 butanediol monoester, see page 20, lines 4-9.
The '766 publication teaches the use of the compound for the claimed method (see claims 1, 4 and 7), and in particular, for a healthy subject, with a high level of fitness) as claimed by applicant, see page 2, lines 25-28; page 6, lines 11-27 (e.g., military members, athletes, body builders, etc.); page 7, lines 31-32.
Conclusion and Correspondence
In summary, no claims are allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to WILLIAM LEE whose telephone number is (571)270-3876. The examiner can normally be reached M-F.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Adam C. Milligan can be reached at (571) 270-7674. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/WILLIAM Y LEE/Examiner, Art Unit 1623
/ADAM C MILLIGAN/Supervisory Patent Examiner, Art Unit 1623
1 This application is a 371 of PCT/EP2013/057250 04/05/2013 claiming priority to UNITED KINGDOM 1206192.5 04/05/2012.
2 "Where, as here, the claimed and prior art products are identical or substantially identical, or are produced by identical or substantially identical processes, the PTO can require an applicant to prove that the prior art products do not necessarily or inherently possess the characteristics of his claimed product... Whether the rejection is based on 'inherency' under 35 USC 102, on 'prima facie obviousness' under 35 USC 103, jointly or alternatively, the burden of proof is the same, and its fairness is evidenced by the PTO's inability to manufacture products or to obtain and compare prior art products." [footnote omitted], (see In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433-434 (CCPA 1977):] See also MPEP 2112: "[T]he PTO can require an applicant to prove that the prior art products do not necessarily or inherently possess the characteristics of his [her] claimed product." See MPEP 2112, citing In re Fitzgerald, 205 USPQ 594, 596 (CCPA 1980), quoting In re Best 195 USPQ 430 as per above.
3 (“The standard to be applied in all cases is the ‘preponderance of the evidence’ test. In other words, an examiner should reject a claim if, in view of the prior art and evidence of record, it is more likely than not that the claim is unpatentable.”)
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