DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Status of the Application
This Office Action is in response to applicant’s arguments filed on 8/5/26. Claims 2, 4-5, 7, 11, 13-15, 20, 22-24 have been cancelled. Claims 1, 3, 6, 8-10, 12, 16-19, 21 are pending. Claims 9 and 21 have been amended. Claims 16-19 have been withdrawn. Claims 1, 3, 6, 8-10, 12, 21 are examined herein.
Applicant’s arguments have been fully considered but found not persuasive. The rejections of the last Office Action are maintained for reasons of record and modified below due to the claim amendments.
Claim Objections
Claim 9 is objected to because of the following informalities: Please correct “2-fol” to “2-fold”. Appropriate correction is required.
Claim Rejections - 35 USC § 102
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 –
(b) the invention was patented or described in a printed publication in this or a foreign country or in public use or on sale in this country, more than one year prior to the date of application for patent in the United States.
Claims 1, 3, 6, 8-10, 12, 21 are rejected under 35 U.S.C. 102(b) as being anticipated by Sparkman (US Patent Application 2008/0317886 A1, of record).
Sparkman teaches: "When runners were given either 3 g HMB per day or a placebo during six weeks of training followed by a 20 km run, blood samples taken after the run showed that the HMB-supplemented individuals had reduced levels of CPK and LDH compared to the placebo control subjects (Knitter,A. E., et al., 2000)." And that "....it was shown that supplementation with HMB reduced the amount of perceived muscle soreness and with less strength loss, suggesting an anti-catabolic effect on muscles which results in less damage (Byrd, P., et al., 1999). (p. 3, col. 2, para [0029]. Sparkman also teaches: "[0060] The forms of HMB could include but are not limited to beta-hydroxy-beta- methylbutanoic acid, calcium beta-hydroxy-beta-methylbutyrate, beta-hydroxy-beta-methylbutyrate amino acid salt, and tricreatine beta-hydroxy-beta-methylbutyrate. (p. 7, column 1, para [0060]. Sparkman teaches composition of HMB as any salt or chelate administered in forms that include liquids, gels, and can be incorporated into foods, such as sports bars (p. 9, column 2, para [0077], lines 3-9, claim 87). Excipients such as gelling agents or flavors, for example raspberry-lemonade or strawberry-lemonade, can be added (examples 1-8).
It is noted that the limitations regarding “increasing strength” and “wherein the administration of HMB acid results in greater increases in muscle strength than the administration of an equivalent amount of HMB in the calcium salt form (CaHMB)” and “increased by at least ten percent” and “increasing systemic exposure” and “wherein the administration of HMB in free acid results in a plasma concentration (Cmax) that is at least 2-fold higher and a time to reach peak plasma concentration (Tmax) that is at least about 90 minutes shorter than administration of an equivalent amount of HMB in the calcium salt form (CaHMB)” are considered inherent in vivo mechanisms of action and will necessarily occur because the same claimed active agent is being administered to the same claimed patient population at the same claimed dosage amount.
Response to Arguments
Applicant argues that Sparkman does not disclose any comparison between HMB-acid and CaHMB for muscle strength, administration of the two forms at equivalent doses, or any teaching that one form produces greater strength outcomes than the other.
This is not persuasive because Sparkman clearly teaches the administration of both forms, thereby meeting all the instant method steps. The difference in muscle strength will necessarily occur even though not explicitly taught by Sparkman.
Applicant argues that the measurable outcomes related to higher Cmax and shorter Tmax are not established by Sparkman to inevitably occur.
This is not persuasive because all of these measurable outcomes must occur if the same method steps are taught by Sparkman, which it does.
Applicant argues that the claims require a comparative functional result: greater muscle strength than CaHMB at an equivalent dose. Sparkman never administers both forms comparatively. Sparkman never teaches specific quantitative thresholds, for example Cmax being 2-fold higher or Tmax being at least 90 min shorter.
This is not persuasive because the instant claims do not necessarily require the administration of CaHMB. The only essential step in the instant claim is to administer HMB at the claimed dose, which Sparkman teaches. Therefore, any functional limitation, whether it is being compared to CaHMB or not, is inherent.
Applicant argues that their own data demonstrate that he claimed result does not inevitably occur with any administration of HMB-acid. The specification shows that the magnitude of PK and strength advantages is dependent on the specific formulation, route of administration, and dosing conditions.
This is not persuasive because any showing of secondary considerations cannot overcome a 102 anticipatory rejection.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
The factual inquiries set forth in Graham vs John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103(a) are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue. 3. Resolving the level of ordinary skill in the pertinent art. 4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims under 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103(a).
Claims 1, 3, 6, 8-10, 12, 21 are rejected under 35 U.S.C. 103(a) as being obvious over Nissen (WO 9414429 A1, of record) in view of Sparkman (US Patent Application 2008/0317886 A1, of record).
The instant claims are drawn to a method of improving muscle utilization of HMB, improving muscle function, improving muscle performance, and improving muscle strength in a human compared to the administration of an equivalent amount of HMB in the calcium salt form (CaHMB).
Determination of the scope and content of the prior art
(MPEP 2141.01)
Nissen et al., teach, "the method of protein sparing, comprising orally or intraveneously administering to a human subject an effective amount of HMB for increasing the retention of nitrogen, said HMB being in an edible or intravenously-administratable form selected from (i) its free acid form..." and where further in claim 3, the effective amount of HMB is from 0.5 to 10 grams (WO 9414429, p 13, claim 3), Nissen teaches a preferred amount of HBM is from 2-6 grams. (p. 7), and can be administered as a free acid (p. 6), which falls within the range of 0.5 to 30 grams described by instant claim 15. Nissen teaches that the administration of beta-hydroxy-beta-methylbutyric acid (HMB) is based on discovery that nitrogen retention in humans is "dramatically improved by the administration of small amounts of p-hydroxy-p-methylbutyric acid (HMB)” (Summary of Invention, p.4-5). In the preparation of HMB, a phosphate buffer was used (page 9, second full paragraph).
Nissen teaches increased bioavailability, wherein this is intrinsically increased plasma levels of HMB that result in a faster time to reach peak plasma levels.
Ascertainment of the difference between the prior art and the claims
(MPEP 2141.02)
The difference between the instant application and Nissen, is that Nissen does not teach improving muscle strength and increasing systemic exposure in a human compared to the administration of an equivalent amount of HMB in the calcium salt form (CaHMB).
This deficiency in Nissen is cured by the teaching of Sparkman.
Sparkman teaches a composition for treating acute inflammation and preventing or reducing the resulting symptoms of delayed onset muscle soreness following overuse of muscles comprising a source of beta-hydroxy-beta methylbutyrate.
Sparkman also teaches giving a horse 10 g of HMB, to relieve muscle soreness (p. 13, column 1, para [0087]), wherein 10 g falls within the range of HMB described by the instant claim 1, of 0.5 to 30 g of HMB free acid, as Sparkman teaches that HMB can be administered as HMB acid "[0060] The forms of HMB could include but are not limited to beta-hydroxy-beta- methylbutanoic acid, calcium beta-hydroxy-beta-methylbutyrate, beta-hydroxy-beta-methylbutyrate amino acid salt, and tricreatine beta-hydroxy-beta-methylbutyrate. (p. 7, column 1, para [0060].”
Therefore, since the perceived muscle soreness and strength loss is reduced, it is obvious that one of ordinary skill in the art would know to measure this effect by using well-known isometric or isotonic contraction testing protocols, such as planks and lifting weights, to measure muscle strength.
Finding of prima facie obviousness
Rational and Motivation (MPEP 2142-2143)
It would have been obvious to one of ordinary skill in the art at the time the claimed invention was made to use the free acid form of HMB, as taught by Sparkman or Nissen, and produce the instant invention.
One of ordinary skill in the art would have been motivated to do this because Sparkman teaches that HMB is used for compositions with HMB salts or essential amino salts (p. 9, para [0077], lines 3-10, and p. 15, column 2, claim 87). A person of ordinary skill would be motivated to provide the oral form of HMB, as taught by Nissen in any conventional form, or taught by Sparkman to include HMB acid (p. 14, claim 66), including as a gel, to a subject in need thereof.
It is noted that the limitations regarding “increasing strength” and “wherein the administration of HMB acid results in greater increases in muscle strength than the administration of an equivalent amount of HMB in the calcium salt form (CaHMB)” and “increased by at least ten percent” and “increasing systemic exposure” and “wherein the administration of HMB in free acid results in a higher peak plasma concentration (Cmax) and a shorter time to reach peak plasma concentration (Tmax) than administration of an equivalent amount of HMB in the calcium salt form (CaHMB)” are considered inherent in vivo mechanisms of action and will necessarily occur because the same claimed active agent is being administered to the same claimed patient population at the same claimed dosage amount.
Response to Arguments
Applicant argues that the claims do not seek to optimize the dose, formulation, or tolerability. They claim the discovery that form alone, at the same dose, produces different physiological outcomes. Here, the specification demonstrates that HMB-acid produced approximately 80% greater net percent increase in strength per week compared to CaHMB. This result was not merely quantitatively greater than expected, but qualitatively different from what the art predicted. Finally, the prior art does not teach that the pharmacokinetic differences are predictable.
This is not persuasive because Applicant is reminded that the prior art clearly teaches the administration of HMB free acid at the claimed dosage. Therefore, there is no need to provide a motivation or reasoning to interchange to or from a particular salt form. The muscle strength, Cmax, and Tmax of HMB free acid administration is being compared to what the muscle strength, Cmax, and Tmax would have been if CaHMB was administered. Either way, the limitation is met because the increase in muscle strength, Cmax, and Tmax of HMB free acid is obvious to occur since the method steps of the claims have been taught by the cited prior art.
Conclusion
THIS ACTION IS MADE FINAL. 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 extension fee 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 Yong S. Chong whose telephone number is (571)-272-8513. The examiner can normally be reached Monday to Friday: 9 AM to 5 PM EST.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Adam 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.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at (866)-217-9197 (toll-free).
/Yong S. Chong/Primary Examiner, Art Unit 1623
Prosecution Insights