DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Priority
This application, filed December 15, 2022, is a national stage application of PCT/US21/37431, filed June 15, 2021, and claims the benefit of U.S. provisional application 63/038989, filed June 15, 2020.
Status of the Application
Applicant’s communication, received January 15, 2026, wherein claims 1, 6, 11, 16, and 21 are amended, is acknowledged.
Claims 1-25 are pending in this application and examined on the merits herein.
Information Disclosure Statement
The information disclosure statements filed October 3, 2025, and April 14, 2026 fail to comply with the provisions of 37 CFR 1.98(a)(4) because each lacks the appropriate size fee assertion. These documents have been placed in the application file, but the information referred to therein has not been considered as to the merits.
Claim Interpretation
The present claims require administering HMB to an animal receiving chemotherapy. In the absence of an express definition of “animal” in the specification, this term is given is customary meaning in the art. The Oxford English Dictionary defines animal as “a living organism which feeds on organic matter, typically having specialized sense organs and a nervous system and able to respond rapidly to stimuli; any living creature, including man” (p. 1, definition 1.a; cited in previous office action). Therefore, animal is interpreted herein to include humans.
Withdrawn Objections
Applicant’s amendment, received January 15, 2026, with respect to the objections to claims 1, 6, 11, 16, and 21 for minor informalities, has been fully considered and found to be persuasive to remove the objection because claims 1, 6, 11, 16, and 21 are amended to correct the informalities. Therefore the objection is withdrawn.
Withdrawn Rejections
Applicant’s amendment, received January 15, 2026, with respect to the rejection to claims 11-13 and 21-23 under 35 U.S.C. § 102 as anticipated by May, has been fully considered and found to be persuasive to remove the rejection because claims 11 and 21 are amended to require administration of HMB attenuates chemotherapy-induced muscle proteolysis and preserves lean body mass during chemotherapy treatment, which the embodiments of May cited in the previous rejection do not teach. Therefore the rejection is withdrawn.
Applicant’s amendment, received January 15, 2026, with respect to the rejection to claims 11, 15, 21, and 25 under 35 U.S.C. § 103 as unpatentable over May in view of Davis, has been fully considered and found to be persuasive to remove the rejection because claims 11 and 21 are amended to require administration of HMB attenuates chemotherapy-induced muscle proteolysis and preserves lean body mass during chemotherapy treatment, which the embodiments of May and Davis cited in the previous rejection do not teach. Therefore the rejection is withdrawn.
Applicant’s amendment, received January 15, 2026, with respect to the rejection to claims 1-4, 11, 14, 16-19, 21, and 24 under 35 U.S.C. § 103 as unpatentable over May in view of Ajouz, has been fully considered and found to be persuasive to remove the rejection because claim 1 is amended to require administration of HMB does not reduce antitumor efficacy of the chemotherapy agent relative to administration of the chemotherapy agent alone, claims 11 and 21 are amended to require administration of HMB attenuates chemotherapy-induced muscle proteolysis and preserves lean body mass during chemotherapy treatment, and claim 16 is amended to require administration of HMB reduces chemotherapy-induced activation of inflammatory cytokines, which the embodiments of May and Ajouz cited in the previous rejection do not teach. Therefore the rejection is withdrawn.
Applicant’s amendment, received January 15, 2026, with respect to the rejection to claim 20 under 35 U.S.C. § 103 as unpatentable over May in view of Ajouz and Davis, has been fully considered and found to be persuasive to remove the rejection because claim 16 is amended to require administration of HMB reduces chemotherapy-induced activation of inflammatory cytokines, which the embodiments of May, Ajouz, and Davis cited in the previous rejection do not teach. Therefore the rejection is withdrawn.
Applicant’s amendment, received January 15, 2026, with respect to the rejection to claim 5 under 35 U.S.C. § 103 as unpatentable over May in view of Ajouz and Rivankar, has been fully considered and found to be persuasive to remove the rejection because claim 1 is amended to require administration of HMB does not reduce antitumor efficacy of the chemotherapy agent relative to administration of the chemotherapy agent alone, which the embodiments of May, Ajouz, and Rivankar cited in the previous rejection do not teach. Therefore the rejection is withdrawn.
Applicant’s amendment, received January 15, 2026, with respect to the rejection to claims 6-8 under 35 U.S.C. § 103 as unpatentable over May in view of Tisdale, has been fully considered and found to be persuasive to remove the rejection because claim 6 is amended to require administration of HMB mitigates chemotherapy-induced physiological stress associated with systemic catabolic response, which the embodiments of May and Tisdale cited in the previous rejection do not teach. Therefore the rejection is withdrawn.
Applicant’s amendment, received January 15, 2026, with respect to the rejection to claim 9 under 35 U.S.C. § 103 as unpatentable over May in view of Tisdale and Ajouz, has been fully considered and found to be persuasive to remove the rejection because claim 6 is amended to require administration of HMB mitigates chemotherapy-induced physiological stress associated with systemic catabolic response, which the embodiments of May, Tisdale, and Ajouz cited in the previous rejection do not teach. Therefore the rejection is withdrawn.
Applicant’s amendment, received January 15, 2026, with respect to the rejection to claim 10 under 35 U.S.C. § 103 as unpatentable over May in view of Tisdale and Davis, has been fully considered and found to be persuasive to remove the rejection because claim 6 is amended to require administration of HMB mitigates chemotherapy-induced physiological stress associated with systemic catabolic response, which the embodiments of May, Tisdale, and Davis cited in the previous rejection do not teach. Therefore the rejection is withdrawn.
Applicant’s amendment, received January 15, 2026, with respect to the rejection to claims 1-3 and 5 under 35 U.S.C. § 103 as unpatentable over Nunes in view of Rivankar, has been fully considered and found to be persuasive to remove the rejection because claim 1 is amended to require administration of HMB does not reduce antitumor efficacy of the chemotherapy agent relative to administration of the chemotherapy agent alone, which the embodiments of Nunes and Rivankar cited in the previous rejection do not teach. Therefore the rejection is withdrawn.
Applicant’s amendment, received January 15, 2026, with respect to the rejection to claims 1-3 and 5 under 35 U.S.C. § 103 as unpatentable over Nunes in view of Rivankar and Ajouz, has been fully considered and found to be persuasive to remove the rejection because claim 1 is amended to require administration of HMB does not reduce antitumor efficacy of the chemotherapy agent relative to administration of the chemotherapy agent alone, which the embodiments of Nunes, Rivankar, and Ajouz cited in the previous rejection do not teach. Therefore the rejection is withdrawn.
Applicant’s amendment, received January 15, 2026, with respect to the previous nonstatutory double patenting rejections over the claims of U.S. Patents 11,406,609, 12,220,391, and 11,547,713, and copending U.S. patent applications 18/095314 and 18/936779 in view of combinations of May, Davis, Ajouz, Rivankar, and Tisdale, have been fully considered and found to be persuasive to remove the rejection because claim 1 is amended to require administration of HMB does not reduce antitumor efficacy of the chemotherapy agent relative to administration of the chemotherapy agent alone, which the embodiments of Nunes, Rivankar, and Ajouz cited in the previous rejection do not teach. Therefore the rejection is withdrawn.
The following are new and/or modified grounds of rejection, necessitated by Applicant’s amendments received January 15, 2026, wherein independent claims 1, 6, 11, 16, and 21 are amended.
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 the first paragraph of pre-AIA 35 U.S.C. 112:
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 of carrying out his invention.
Claims 11-15 and 21-25 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claims 11 and 21 are amended to recite: “wherein administration of HMB attenuates chemotherapy-induced muscle proteolysis and preserves lean body mass during chemotherapy treatment.”
The limitation wherein HMB attenuates chemotherapy-induced muscle proteolysis were not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. The specification discloses that doxorubicin can activate proteolysis (p. 6, second paragraph), and the specification provides examples in which the pro-inflammatory markers are attenuated by HMB (Figure 4), but the specification does not specifically describe or demonstrate the mechanism of HMB as attenuating chemotherapy-induced muscle proteolysis.
Because claims 12-15, and 22-25 depend from claims 11 and 21, claims 12-15 and 22-25 are also rejected under 35 U.S.C. 112(a) as including new matter.
Claim 1 includes the limitation “wherein administration of HMB does not reduce antitumor efficacy of the chemotherapy agent relative to administration of the chemotherapy agent alone.” This is not new matter because the specification provides an example in which administration of HMB and doxorubicin does not reduce the efficacy of doxorubicin (e.g., see Figure 1A and 1B).
Claim 6 includes the limitation wherein administration of HMB mitigates chemotherapy-induced physiological stress associated with systemic catabolic response. This is not new matter because the specification describes the effect of HMB as reducing expression of IL-1B and serum levels of C-reactive protein compared with treatment of doxorubicin alone, protecting against inflammation-driven catabolic potential related to doxorubicin chemotherapy (e.g., see pp. 19-20).
Claim 16 includes the limitation wherein administration of HMB reduces chemotherapy-induced activation of inflammatory cytokines. This is not new matter because the specification provides an example in which administration of HMB reduced inflammatory cytokines (e.g., see Figure 4).
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 11-13 and 21-23 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by May (May, P. E.; et al. The American Journal of Surgery 2002, vol. 183, pp. 471-479; cited in previous office action), as evidenced by Davis (Davis, M. P.; et al. Annals of Palliative Medicine 2019, vol. 8, pp. 86-101; cited in previous office action).
Claim 11 claims a method for protecting against chemotherapy-induced weight loss in an animal undergoing chemotherapy treatment comprising administering to an animal in need
thereof being treated with a chemotherapy agent from about 0.5 g to about 30 g of β-hydroxy-β-
methylbutyrate (HMB), wherein administration of HMB attenuates chemotherapy-induced
muscle proteolysis and preserves lean body mass during chemotherapy treatment. Claim 12 requires said HMB is selected from the group consisting of its free acid form, its salt, its ester and its lactone, and claim 13 requires said HMB is a calcium salt.
Claim 21 claims a method for providing an anti-cachectic treatment against weight loss induced by administration of a chemotherapy agent in an animal undergoing chemotherapy treatment comprising administering to an animal in need thereof being treated with a chemotherapy agent from about 0.5 g to about 30 g of β-hydroxy-β-methylbutyrate (HMB), wherein administration of HMB attenuates chemotherapy-induced muscle proteolysis and preserves lean body mass during chemotherapy treatment. Claim 22 requires said HMB is selected from the group consisting of its free acid form, its salt, its ester and its lactone, and claim 23 requires said HMB is a calcium salt.
May teaches a study for reversing cancer-related wasting using oral supplementation with a combination of β-hydroxy-β-methylbutyrate (HMB), arginine, and glutamine (p. 471, Title). May teaches that patients with solid tumors who had demonstrated a weight loss of at least 5% were considered for the study and were randomly assigned in a double-blind fashion to either an isonitrogenous control mixture of nonessential amino acids or an experimental treatment containing β-hydroxy-β-methylbutyrate (3 g/d), L-arginine (14 g/d), and L-glutamine (14 g/d [HMB/Arg/Gln]) (p. 471, Abstract, Methods section, lines 1-3). May teaches that the patients supplemented with HMB/Arg/Gln gained 0.95 ± 0.66 kg of body mass in 4 weeks, whereas control subjects lost 0.26 ± 0.78 kg during the same time period (p. 471, Abstract, Results section, lines 1-2). May teaches there was no negative effect of treatment on the incidence of adverse effects or quality of life measures (p. 471, Abstract, Results section, lines 6-7).
Specifically relating to their method, May teaches that patients with advanced solid tumors (stage IV) who had documented weight loss greater than 5% and with a likely prognosis of 3 months or greater survival were considered for the study, and that chemotherapy and radiation therapy were acceptable during the study (p. 472, paragraph bridging left and right columns, lines 1-5). May teaches that the treatment group received HMB specifically in the form of a calcium salt (p. 472, right column, second full paragraph, lines 4-5).
May concludes by stating that daily supplementation with HMB/Arg/Gln increases
weight gain and fat-free mass in advanced cancer patients with cachexia, and that the patient population studied was heterogeneous consisting of stage IV cancer patients receiving various treatment modalities with chemotherapeutic agents (p. 477, right column, third full paragraph, lines 1-6) (emphasis added). An increase in fat-free mass is interpreted herein as equivalent to lean body mass as recited in claims 11 and 21, and thus HMB preserves lean body mass during chemotherapy.
Therefore, May teaches administration of HMB in the calcium salt form with a chemotherapy for protecting against chemotherapy-induced weight loss and for providing an anti-cachectic treatment.
May does not teach specifically teach the limitation wherein administration of HMB attenuates chemotherapy-induced muscle proteolysis during chemotherapy treatment. However, this is inherent to the method of administering HMB to a patient during chemotherapy. As evidence, Davis teaches the cisplatin, irinotecan, doxorubicin, and etoposide cause direct muscle loss through activation of the transcription factor NF kappa B which upregulates ubiquitin and proteasomes, increases proteolysis and inflammatory cytokines which increases E3 ligases and increases ubiquitin protein binding for proteolysis (p. 87, right column, third paragraph, lines 1-7). Accordingly, because May teaches daily supplementation with HMB/Arg/Gln increases weight gain and fat-free mass, the examiner asserts that the method administration of HMB in the method of May must inherently attenuate the chemotherapy-induced muscle proteolysis during chemotherapy treatment acknowledged by Davis.
MPEP 2112.01 (especially at I) citing In re Best, 562 F.2d 1252, 195 USPQ 430
(C.C.P.A. 1977) and In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990)
discusses the support of rejections wherein the prior art discloses subject matter which there is
reason to believe necessarily includes functions or characteristics that are newly recited or is
identical to an invention as instantly claimed. In such a situation, the burden is shifted to the
applicants to show the invention of the applicant and the prior art are not the same or that the
prior art invention does not necessarily possess the characteristics of the claimed invention. In this instance, because May teaches daily supplementation with HMB/Arg/Gln increases weight gain and fat-free mass, the examiner asserts that the method administration of HMB in the method of May inherently attenuates chemotherapy-induced muscle proteolysis during chemotherapy treatment, absent evidence to the contrary.
Response to Applicant’s arguments: Regarding the previous rejection of claims 11-13 and 21-23 under 35 U.S.C. § 102, Applicant argues that May does not disclose, teach, or suggest
weight loss attributable to chemotherapy administration, nor does it evaluate chemotherapy-induced muscle proteolysis, inflammatory injury, or preservation of lean body mass during
chemotherapy treatment. (Applicant’s remarks, p. 5)
Moreover, Applicant argues the cited references do not establish that attenuation of chemotherapy-induced muscle proteolysis, preservation of lean body mass during chemotherapy treatment, reduction of chemotherapy-induced inflammatory cytokines, or maintenance of antitumor efficacy necessarily and inevitably occur upon administration of HMB. To the contrary, the art reflects variability and uncertainty in nutritional intervention during chemotherapy. (Applicant’s remarks, p. 7).
Applicant’s arguments have been fully considered but they are not found persuasive. As stated, May teaches a method of administering HMB to patients undergoing chemotherapy and teaches that daily supplementation with HMB/Arg/Gln increases weight gain and fat-free mass, which, as described, is interpreted as equivalent to preserving lean body mass during chemotherapy treatment. Moreover, because Davis recognizes the effect of chemotherapies inducing muscle proteolysis. Because May observes said increase in weight gain and fat-free mass, the limitation wherein administration of HMB attenuates chemotherapy-induced
muscle proteolysis would necessarily be present in the method of May.
Moreover, Applicant has not provided evidence that the art is unpredictable regarding the effect of HMB on chemotherapy-induced muscle proteolysis and preserves lean body mass during chemotherapy treatment. In this instance, the art teaches administration of HMB with chemotherapy increases fat-free mass, and the art further recognizes the effect of chemotherapies on muscle-induced proteolysis. Accordingly, these additional limitations are inherent to the method of May, and the present rejection of claims 11-13 and 21-23 as anticipated by May, evidenced by Davis, is maintained.
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 factual inquiries for establishing a background for determining obviousness under 35
U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 11-13, 15, 21-23, and 25 are rejected under 35 U.S.C. 103 as being unpatentable over May (May, P. E.; et al. The American Journal of Surgery 2002, vol. 183, pp. 471-479; cited in previous office action) in view of Davis (Davis, M. P.; et al. Annals of Palliative Medicine 2019, vol. 8, pp. 86-101; cited in IDS received December 15, 2022).
The examiner maintains that May anticipates claims 11-13 and 21-23, as described in the above rejection under 35 U.S.C. § 102. However, for the sake of argument, if the loss of muscle mass in patients included in May were not due to reduced chemotherapy-induced muscle proteolysis, then claims 11-13 and 21-23 would have been obvious over May in view of Davis. In addition, claims 15 and 25 are obvious over May in view of Davis.
May teaches as described in the above rejection under 35 U.S.C. 102. In addition, May teaches the weight gain of patients in their study was the result of a significant increase in fat-free mass in the HMB/Arg/Gln-supplemented group (1.12 ± 0.68 kg), whereas the subjects supplemented with the control lost 1.34 ± 0.78 kg of fat-free mass, and that the effect of HMB/Arg/Gln on fat-free mass increase was maintained over the 24 weeks (1.60 ± 0.98 kg) (p. 471, Abstract, Results section, lines 1-6).
May further teaches that cancer cachexia has been cited as the most frequent cause of morbidity and mortality in patients with cancer, and that maintenance of lean body mass above the defined critical malnutrition thresholds could enhance patient survival (p. 471, left column, lines 5-8 and right column, lines 1-3). Therefore, in view of May, one of ordinary skill in the art would have recognized that maintenance of lean body mass, facilitated by administration of HMB, could enhance patient survival.
May does not teach the limitation wherein administration of HMB attenuates chemotherapy-induced muscle proteolysis during chemotherapy treatment, as required by claims 11 and 21, and the specific chemotherapy agent as doxorubicin, as required by claims 15 and 25.
Davis teaches sarcopenia associated with chemotherapy and targeted agents for cancer therapy (p. 86, Title). Davis teaches that the chemotherapeutic agents cisplatin, irinotecan, doxorubicin, and etoposide cause direct muscle loss through activation of the transcription factor NF kappa B which upregulates ubiquitin and proteasomes, increases proteolysis and inflammatory cytokines (IL-1 beta, IL6, and TNF alpha), and which increases E3 ligases and ubiquitin protein binding for proteolysis. Davis teaches that TNF alpha accelerates catabolism (protein loss, insulin resistance), muscle contractile dysfunction, and disrupts myogenesis leading to muscle weakness (p. 87, right column, third paragraph, lines 1-10). Therefore, in view of Davis, one of ordinary skill in the art would have recognized that chemotherapies, including the chemotherapy doxorubicin, causes direct muscle loss through activation of NF kappa B, which accelerates catabolism, muscle contractile dysfunction, and disrupts myogenesis.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the present application to administer HMB to a patient undergoing chemotherapy treatment with doxorubicin to protect against chemotherapy-induced weight loss and to provide an anti-cachectic treatment. One of ordinary skill in the art would have been motivated to administer HMB to a patient undergoing chemotherapy treatment with doxorubicin to protect against chemotherapy-induced weight loss and to provide an anti-cachectic treatment because May teaches the value of HMB administration in patients undergoing chemotherapy, including an increase in weight and lean body mass, and because Davis teaches that doxorubicin causes direct muscle loss. Moreover, because May teaches the importance of lean body mass specifically in cancer patients and cancer patient survival, and because the administration of HMB as taught by May increases lean body mass, one of ordinary skill in the art would have recognized that HMB may be effective in reducing or stopping the muscle loss caused by doxorubicin, as taught by Davis
Therefore, one of ordinary skill in the art would have been motivated to apply the method of May to an animal undergoing treatment with the chemotherapy doxorubicin to counteract the effects of doxorubicin-induced muscle loss. In this instance, the rationale “use of a known technique to improve similar methods in the same way” would apply. Because May teaches the benefits of HMB in patients undergoing chemotherapy, specifically for reducing weight loss and reducing lean body mass loss, and because Davis teaches that doxorubicin causes muscle loss, one of ordinary skill in the art would have considered administering HMB to a patient undergoing treatment with doxorubicin for reducing muscle loss, with a reasonable expectation that the administration of HMB may protect against chemotherapy-induced weight loss and provide an anti-cachectic treatment, as taught by May.
Therefore the invention taken as a whole is prima facie obvious.
Response to Applicant’s arguments: With respect to the rejection of claims 11-13, 15, 21-23, and 25, Applicant argues as described in the above rejection under 35 U.S.C. § 102.
In addition, Applicant argues that Davis does not teach nutritional mitigation of
these pathways during chemotherapy, nor does it suggest that administration of HMB would attenuate chemotherapy-induced muscle proteolysis or preserve lean body mass during treatment.
Applicant further argues the examiner's rationale relies on hindsight reconstruction rather than a reasonable expectation of success. Identification of chemotherapy-induced muscle injury does not render its nutritional mitigation predictable, particularly in the oncology context where supplementation frequently fails or interferes with therapy.
Applicant’s arguments have been fully considered but they are not found persuasive. May teaches that cancer cachexia has been cited as the most frequent cause of morbidity and mortality in patients with cancer, and that maintenance of lean body mass above the defined critical malnutrition thresholds could enhance patient survival. May further teaches their study shows that daily supplementation with HMB/Arg/Gln increases weight gain and fat-free mass in advanced cancer patients with cachexia. Therefore, in view of May, one of ordinary skill in the art would have recognized supplementation with HMB as a strategy to treat cachexia in cancer patients undergoing cachexia.
Davis teaches that chemotherapies induce cachexia, further teaching the mechanism of this effect. Accordingly, one of ordinary skill in the art would have had a reasonable expectation of success administering an anti-cachexia therapy – treatment with HMB – to patients experiencing cachexia or at risk of suffering from cachexia.
Moreover, Applicant merely states that nutritional supplementation frequently fails or interferes with therapy, but provides no evidence of said effect. MPEP 2145(I) states: “Arguments presented by applicant cannot take the place of evidence in the record. See In re De Blauwe, 736 F.2d 699, 705, 222 USPQ 191, 196 (Fed. Cir. 1984); In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965); In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997) ("An assertion of what seems to follow from common experience is just attorney argument and not the kind of factual evidence that is required to rebut a prima facie case of obviousness.").”
Accordingly, for the reasons described above, the present rejection of claims 11-13, 15, 21-23, and 25 as unpatentable over May in view of Davis is maintained.
Claims 14, 16-20, and 24 are rejected under 35 U.S.C. 103 as being unpatentable over May in view Davis as applied to claims 11-13, 15, 21-23, and 25 above, and further in view of Ajouz (Ajouz, H.; et al. Journal of Nutritional Oncology 2019, vol. 4, no. 1, pp. 1-8; cited in IDS received December 15, 2022).
May teaches as described in the above rejections under 35 U.S.C. § 102 and 35 U.S.C. § 103. Specifically, May teaches daily administration of a composition comprising HMB that increases weight gain and fat-free mass in advanced cancer patients with cachexia receiving various treatment modalities with chemotherapeutic agents (p. 477, right column, third full paragraph, lines 1-6).
Davis teaches as described in the above rejections under 35 U.S.C. § 102 and 35 U.S.C. § 103.
Neither May nor Davis teach HMB is in the free acid form, as recited in claims 14 and 24. In addition, neither May nor Davis teach a method for protecting against chemotherapy-induced inflammation in an animal undergoing chemotherapy treatment, wherein administration of HMB reduces chemotherapy-induced activation of inflammatory cytokines, as required by claim 16.
Ajouz teaches the role of β-hydroxy-β-methylbutyrate (HMB) in cancer cachexia and sarcopenia (p. 1, Title). Ajouz teaches that although some treatment options exist to counteract cachexia, very few options counteract sarcopenia (loss of muscle mass), and HMB may be a viable component in multi-modal approaches targeting treatment of cancer cachexia/sarcopenia.
Ajouz teaches that HMB promotes myogenic events, suppresses proteasome activity, and activates protein synthesis, represses inflammation, reduces tumor growth, and increases lifespan (p. 1, Abstract, lines 2-5).
Ajouz teaches that cancer cachexia is an inflammation-induced physiological and metabolic response which transfers amino acids from muscle catabolism into the amino acid pool required for acute phase reaction protein synthesis. Ajouz teaches that increased pro-inflammatory cytokine activity, as part of systematic inflammation, is a hallmark of cancer cachexia (p. 1, right column, last paragraph, lines 1-6). Ajouz further teaches that repressing inflammation could counteract the manifestation of cancer cachexia, and that HMB possesses an anti-inflammatory effect, reducing TNFα and IFN-γ production by human mononuclear cells in vitro and blocking some IL-6-mediated pathways (p. 2, left column, first full paragraph, lines 1-6).
Furthermore, relating to the specific salt form of HMB, Ajouz teaches that subjects receiving HMB therapy as a free acid gel presented quicker and greater plasma concentrations and improved clearance of plasma HMB versus those receiving calcium HMB gelatine capsules, and that this gel formulation could improve HMB availability and efficacy to tissue (p. 6, left column, second paragraph, lines 1-6).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the present application to administer HMB for the purposes of protecting against chemotherapy-induced inflammation in an animal undergoing chemotherapy treatment. One of ordinary skill in the art would have been motivated to administer HMB for the purposes of protecting against chemotherapy-induced inflammation in an animal undergoing chemotherapy treatment because May teaches the value of administering HMB for reversing cancer-related wasting in patients undergoing chemotherapy, and because Ajouz teaches cancer cachexia is an inflammation-induced response, the anti-inflammatory effect of HMB, and that repressing inflammation could counteract some of the manifestations of cancer cachexia. Therefore, in view of the benefit of administering HMB to a patient undergoing chemotherapy in maintaining lean muscle mass, as taught by May, and in view of the effect HMB has on inflammation and that repressing inflammation could counteract some manifestations of cancer cachexia, as taught by Ajouz, one of ordinary skill in the art would have reasonably considered administering HMB to an animal undergoing chemotherapy for the purposes of reducing inflammation, because reducing inflammation may counteract some manifestations of cancer cachexia.
Regarding the limitation wherein administration of HMB reduces chemotherapy-induced activation of inflammatory cytokines, because Davis teaches that chemotherapies including doxorubicin, and etoposide cause direct muscle loss through activation of the transcription factor NF kappa B which increases proteolysis and inflammatory cytokines, including IL-1 beta, IL 6 and TNF alpha), and because Ajouz teaches HMB possesses an anti-inflammatory effect, reducing TNFα and IFN-γ production by human mononuclear cells in vitro and blocking some IL-6-mediated pathways, one of ordinary skill in the art would have had a reasonable expectation that administration of HMB would reduce chemotherapy-induced activation of inflammatory cytokines.
Moreover, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the present application to substitute the HMB calcium salt, as used in the method taught by May, for HMB in the form of a free acid gel. One of ordinary skill in the art would have been motivated to substitute the HMB calcium salt for HMB in the form of a free acid gel because May teaches the value of administering HMB for reversing cancer-related wasting, and because Ajouz teaches that HMB in the form of a free acid gel present quicker and greater plasma concentrations than HMB calcium gelatin capsules, and thus one of ordinary skill in the art would have considered this form of HMB because of its potentially advantageous pharmacokinetic properties. In this instance, the rationale “simple substitution of one known element for another to obtain predictable results” would apply. In view of Ajouz, one of ordinary skill in the art would have recognized that the free acid form of HMB may be administered for the purposes of treating cancer cachexia and sarcopenia, and thus may replace the HMB calcium salt taught by May with a reasonable expectation that the HMB free acid form will be effective for protecting against weight loss induced by the administration of a chemotherapy agent, for protecting against chemotherapy-induced inflammation in an animal undergoing chemotherapy treatment, and a method for providing an anti-cachectic treatment against weight loss induced by administration of a chemotherapy agent
Therefore the invention taken as a whole is prima facie obvious.
Response to Applicant’s arguments: Regarding the previous rejection of independent claim 16 as unpatentable over May in view of Ajouz, Applicant argues that Ajouz does not disclose modulation of chemotherapy-induced inflammatory cytokine activation (Applicant’s remarks, p. 6).
Applicant’s arguments have been fully considered but they are not found persuasive. Because Davis teaches chemotherapy can inflammatory cytokines, and because Ajouz teaches HMB represses inflammation, one of ordinary skill in the art would have recognized HMB may reduce chemotherapy-induced activation of inflammatory cytokines.
Accordingly, for the reasons described above, the present rejection of claims 14, 16-20, and 24 as unpatentable over May in view of Davis and Ajouz is maintained.
Claims 6-10 are rejected under 35 U.S.C. 103 as being unpatentable over May (May, P. E.; et al. The American Journal of Surgery 2002, vol. 183, pp. 471-479; cited in previous office action) in view of Tisdale (Tisdale, M. J.; et al. Physiological Reviews 2009, vol. 89, pp. 381-410; cited in previous office action), Davis (Davis, M. P.; et al. Annals of Palliative Medicine 2019, vol. 8, pp. 86-101; cited in IDS received December 15, 2022), Ajouz (Ajouz, H.; et al. Journal of Nutritional Oncology 2019, vol. 4, no. 1, pp. 1-8; cited in IDS received December 15, 2022), and Baracos (Baracos V. E.; et al. Annals of Palliative Medicine 2019, vol. 8, pp. 3-12; cited in PTO-892).
Claim 6 claims a method for increasing survival of an animal undergoing chemotherapy treatment comprising administering to an animal in need thereof being treated with a chemotherapy agent from about 0.5 g to about 30 g of β-hydroxy-β-methylbutyrate (HMB), wherein administration of HMB mitigates chemotherapy-induced physiological stress associated with systemic catabolic response. Claim 7 requires said HMB is selected from the group consisting of its free acid form, its salt, its ester and its lactone, and claim 8 requires said HMB is a calcium salt.
May teaches as described in the above rejections under 35 U.S.C. § 102 and 35 U.S.C. § 103. Specifically, May teaches the weight gain of patients in their study was the result of a significant increase in fat-free mass in the HMB/Arg/Gln-supplemented group (1.12 ± 0.68 kg), whereas the subjects supplemented with the control lost 1.34 ± 0.78 kg of fat-free mass, and that the effect of HMB/Arg/Gln on fat-free mass increase was maintained over the 24 weeks (1.60 ± 0.98 kg) (p. 471, Abstract, Results section, lines 1-6).
In addition, May teaches cancer cachexia has been cited as the most frequent cause of morbidity and mortality in patients with cancer, and that maintenance of lean body mass above the defined critical malnutrition thresholds could enhance patient survival (p. 471, left column, lines 5-8 and right column, lines 1-3) (emphasis added). Therefore, in view of May, one of ordinary skill in the art would have recognized that maintenance of lean body mass, facilitated by administration of HMB, could enhance patient survival.
May does not directly teach a method for increasing survival of an animal undergoing chemotherapy comprising administering to an animal in need thereof being treated with a chemotherapy agent HMB, and wherein administration of HMB mitigates chemotherapy-induced physiological stress associated with systemic catabolic response, each as recited in claim 6.
Tisdale teaches that up to 50% of cancer patients suffer from a progressive atrophy of adipose tissue and skeletal muscle, called cachexia, resulting in weight loss, a reduced quality of life, and a shortened survival time (p. 381, Abstract, lines 1-3).
Davis and Ajouz teach as described in the above rejections under 35 U.S.C. § 103 and 35 U.S.C. § 103.
Baracos teaches that a wide variety of systemic antineoplastic agents generate muscle loss directly by expressing direct catabolic actions on muscle cells, as well as secondarily via their systemic (gastrointestinal) side effects that impair food intake during treatment, and that muscle wasting deserves consideration as a potential adverse effect in the use of current cancer therapies and the development of new ones (p. 9, paragraph bridging left and right columns, lines 6-13).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the present application to administer HMB to an animal receiving chemotherapy for the purposes of increasing its survival time. One of ordinary skill in the art would have been motivated to administer HMB to an animal receiving chemotherapy for the purposes of increasing its survival time because Tisdale teaches that up to 50% of cancer patients suffer from cachexia, resulting in a shortened survival time, and because May teaches that administration of a composition comprising HMB counteracts the effects of cachexia in cancer patients undergoing chemotherapy, including increasing a patient’s lean body mass. Therefore, by administering a composition comprising HMB to a patient undergoing chemotherapy, one of ordinary skill in the art would have recognized that said composition may counteract the effects of cachexia, which results in shortened survival time, as taught by Tisdale.
One of ordinary skill in the art would have had a reasonable expectation of success administering a composition comprising HMB to an animal undergoing chemotherapy to increase its survival because Tisdale teaches that up to 50% of cancer patients suffer cachexia, which results in a shortened survival time, and because May teaches that administration of HMB counteracts the effects of cancer-related cachexia. Therefore, one of ordinary skill in the art would have had a reasonable expectation that administration of HMB with a chemotherapy would have counteracted cachexia in cancer patients and thus increased survival time of an animal undergoing chemotherapy.
Regarding the requirement that administration of HMB mitigates chemotherapy-induced physiological stress associated with systemic catabolic response, this is an intended result of the method for increasing survival of an animal undergoing chemotherapy treatment comprising administering to an animal in need thereof being treated with a chemotherapy agent from about 0.5 g to about 30 g of HMB. MPEP 2111.04 discusses claim language that does not limit a claim to a particular structure, including “adapted to” or “adapted for” clauses, “wherein” clauses, and “whereby” clauses.
“The determination of whether each of these clauses is a limitation in a claim depends on the specific facts of the case. See, e.g., Griffin v. Bertina, 285 F.3d 1029, 1034, 62 USPQ2d 1431 (Fed. Cir. 2002) (finding that a "wherein" clause limited a process claim where the clause gave "meaning and purpose to the manipulative steps"). In In re Giannelli, 739 F.3d 1375, 1378, 109 USPQ2d 1333, 1336 (Fed. Cir. 2014), the court found that an "adapted to" clause limited a machine claim where "the written description makes clear that 'adapted to,' as used in the [patent] application, has a narrower meaning, viz., that the claimed machine is designed or constructed to be used as a rowing machine whereby a pulling force is exerted on the handles." In Hoffer v. Microsoft Corp., 405 F.3d 1326, 1329, 74 USPQ2d 1481, 1483 (Fed. Cir. 2005), the court held that when a "‘whereby’ clause states a condition that is material to patentability, it cannot be ignored in order to change the substance of the invention." Id. However, the court noted that a "‘whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.’" Id. (quoting Minton v. Nat’l Ass’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003)). Therefore, because this limitation in claim 6 recites in an intended result of a process step, and because the process of claims 6-10 is obvious over May in view of Tisdale, Davis, Ajouz, and Baracos, the limitation wherein administration of HMB does not reduce antitumor efficacy of the chemotherapy agent relative to administration of the chemotherapy agent alone does not limit the structure of the method.
Moreover, because Davis teaches that the chemotherapeutic agents such as doxorubicin cause direct muscle loss through activation of the transcription factor NF kappa B which upregulates ubiquitin and proteasomes, increases proteolysis and inflammatory cytokines (IL-1 beta, IL6, and TNF alpha), and further teaches that TNF alpha accelerates catabolism, one of ordinary skill in the art would have recognized that administration of chemotherapeutics, such as doxorubicin, induce physiological stress by activating NF kappa B, increasing proteolysis and inflammatory cytokines including TNF alpha, and accelerating catabolism. Because Ajouz teaches HMB possesses an anti-inflammatory effect, reducing TNFα and IFN-γ production by human mononuclear cells in vitro and blocking some IL-6-mediated pathways, one of ordinary skill in the art would have further had a reasonable expectation that administration of HMB would indeed reduce chemotherapy-induced physiological stress and catabolic response associated with, for example, activation of TNF alpha.
Regarding chemotherapy-induced physiological stress associated with a systemic catabolic response, because Baracos teaches systemic antineoplastic agents generate muscle loss directly by expressing direct catabolic actions on muscle cells, one of ordinary skill in the art would have recognized this chemotherapy-induced physiological stress may be a systemic catabolic response, such as when a chemotherapy is administered systemically.
Regarding the free acid form of HMB required by claim 9, it would have been obvious to one of ordinary skill in the art to substitute the HMB calcium salt taught by May for HMB in the form of a free acid gel. One of ordinary skill in the art would have been motivated to substitute the HMB calcium salt for HMB in the form of a free acid gel because May teaches the value of administering HMB for reversing cancer-related wasting in a patient, thus reasonably increasing survival of said patient, and because Ajouz teaches that HMB in the form of a free acid gel presents quicker and greater plasma concentrations than HMB calcium gelatin capsules. Accordingly, one of ordinary skill in the art would have considered the free acid formulation of HMB taught by Ajouz because of its potentially advantageous pharmacokinetic properties. In this instance, the rationale “simple substitution of one known element for another to obtain predictable results” would apply. In view of Ajouz, one of ordinary skill in the art would have recognized that the free acid form of HMB may be administered for the purposes of treating cancer cachexia and sarcopenia, thus increasing patient survival, and may replace the HMB calcium salt taught by May with a reasonable expectation that the HMB free acid form will be effective for reversing cancer-related wasting and increasing animal survival time.
Therefore the invention taken as a whole is prima facie obvious.
Response to Applicant’s arguments: Regarding the previous rejection of independent claim 6 as unpatentable over May in view of Tisdale, Applicant argues that Tisdale describes correlations between cachexia and mortality but does not teach that nutritional supplementation during chemotherapy increases survival, nor that survival during chemotherapy may be increased without compromising antitumor efficacy (Applicant’s remarks, p. 7).
Applicant’s arguments have been fully considered but they are not found persuasive. Because Tisdale recognizes cachexia as contributing to a shortened survival time and May teaching the anti-cachectic effects of HMB, one of ordinary skill in the art would have administered HMB with a chemotherapy to mitigate the effects of cachexia, which would be expected to increase survival. In addition, because Davis recognizes chemotherapy-induced stress associated with a systemic catabolic response, and Ajouz teaches, for example, that HMB may repress inflammation, one of ordinary skill in the art would have recognized HMB may reasonably mitigate chemotherapy-induced physiological stress associated with systemic catabolic response.
Accordingly, for the reasons described above, the present rejection of claims 6-10 as unpatentable over May in view of Tisdale, Davis, Ajouz, and Baracos is maintained.
Claims 1-3 and 5 are rejected under 35 U.S.C. 103 as being unpatentable over Nunes (Nunes, E. A.; et al. Nutrition Research 2008, vol. 28, pp. 487-493; cited in previous office action) in view of Rivankar (Rivankar, S. Journal of Cancer Research and Therapeutics 2014, vol., 10, pp. 853-858; cited in previous office action).
Nunes teaches a study in which the anticatabolic agent β-hydroxy-β-methylbutyrate (HMB) was supplemented to adult Walker 256 tumor-bearing rats during 8 weeks aiming to determine if tumor burden could be reduced. Nunes teaches that male Wistar rats were randomly assigned to nontumor and tumor-bearing groups inoculated with Walker 256 tumor cells (p. 487, Abstract, lines 2-5; p. 488, right column, Section 2.2, second paragraph, lines 1-4). Walker teaches that the mice were fed regular chow or regular chow plus HMB supplemented (76 mg/kg body weight), and that β-Hydroxy-β-methylbutyrate supplementation induced a lower tumor weight (p. 487, Abstract, lines 4-7). Nunes teaches that reduction in tumor cell proliferation ex vivo was accompanied by increased nuclear factor-κB inhibitor-α content by more than 100% (p. 487, Abstract, lines 8-10).
Nunes teaches that the calcium HMB monohydrate, food grade–based supplement was supplied by Metabolic Technologies, Inc (p. 488, right column, Section 2.2, first paragraph, lines 19-21).
Nunes concludes by stating that HMB supplementation, at a similar dose used in humans to increase muscle mass, caused antitumor and anticachectic effects, with tumor-cell nuclear factor-κB pathway participation, which might be a potential nutritional strategy in cancer therapy (p. 487, Abstract, lines 11-13).
Nunes does not teach administration of an additional chemotherapy with HMB for the purposes of inhibiting tumor growth in an animal, as required by claim 1.
Rivankar teaches doxorubicin as a cancer therapy. Specifically, Rivankar teaches that doxorubicin is most commonly used to treat cancers of the bladder, breast, stomach, lung, ovaries, thyroid, soft tissue sarcoma, multiple myeloma, and Hodgkin’s lymphoma (p. 854, left column, lines 1-3).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the present application to administer the combination of HMB and doxorubicin to an animal for the purposes of inhibiting tumor growth. One of ordinary skill in the art would have been motivated to administer the combination of HMB and doxorubicin to an animal for the purposes of inhibiting tumor growth because Nunes teaches that HMB inhibits growth of tumors when administered to rats, and because Rivankar teaches doxorubicin also has activity against solid tumors. In this instance, the rationale “combining prior art elements according to known methods to yield predictable results” would apply. Because both HMB and doxorubicin are recognized in the art for inhibiting tumor growth, administration of these agents in combination for the purposes of inhibiting tumor growth would have been prima facie obvious.
One of ordinary skill in the art would have had a reasonable expectation of success administering the combination of HMB and doxorubicin to an animal for the purposes of inhibiting tumor growth because each of HMB and doxorubicin are recognized in the art to inhibit tumor growth on their own, and thus one of ordinary skill in the art would have had a reasonable expectation that administering the combination of HMB and doxorubicin to an animal for inhibiting tumor growth would successfully reduce tumor growth in an animal.
Regarding the dose of HMB as required by claim 1 from about 0.5 g to about 30 g, , Nunes teaches a dose of HMB administered to rats of 76 mg/kg body weight. Although this falls below the dose required by claim 1, one of ordinary skill in the art would have recognized the need for a higher dose if administered to a larger animal, such as a human. For example, a 50 kg human, if administered a similar dose, would receive 3.8 g of HMB. Therefore, one of ordinary skill in the art would have reasonably considered doses that fall within the claimed range if said treatment taught by Nunes were administered to a larger animal.
Moreover, with respect to the dose of HMB, MPEP 2144.05 II at A states: “Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).” In this instance, in view of the dose taught by Nunes, one of ordinary skill in the art would have considered doses of HMB that fall within the claimed range.
Regarding the limitation wherein administration of HMB does not reduce antitumor
efficacy of the chemotherapy agent relative to administration of the chemotherapy agent alone as recited in claim 1, this is an intended result of the process of the method for inhibiting tumor growth in an animal undergoing chemotherapy treatment comprising administering to an animal in need thereof being treated with a chemotherapy agent from about 0.5 g to about 30 g of HMB. MPEP 2111.04 discusses claim language that does not limit a claim to a particular structure, including “adapted to” or “adapted for” clauses, “wherein” clauses, and “whereby” clauses.
“The determination of whether each of these clauses is a limitation in a claim depends on the specific facts of the case. See, e.g., Griffin v. Bertina, 285 F.3d 1029, 1034, 62 USPQ2d 1431 (Fed. Cir. 2002) (finding that a "wherein" clause limited a process claim where the clause gave "meaning and purpose to the manipulative steps"). In In re Giannelli, 739 F.3d 1375, 1378, 109 USPQ2d 1333, 1336 (Fed. Cir. 2014), the court found that an "adapted to" clause limited a machine claim where "the written description makes clear that 'adapted to,' as used in the [patent] application, has a narrower meaning, viz., that the claimed machine is designed or constructed to be used as a rowing machine whereby a pulling force is exerted on the handles." In Hoffer v. Microsoft Corp., 405 F.3d 1326, 1329, 74 USPQ2d 1481, 1483 (Fed. Cir. 2005), the court held that when a "‘whereby’ clause states a condition that is material to patentability, it cannot be ignored in order to change the substance of the invention." Id. However, the court noted that a "‘whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.’" Id. (quoting Minton v. Nat’l Ass’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003)). Therefore, because the claim 1 recites an intended result of a process step, and because the process of claims 1-3 and 5 is obvious over Nunes in view of Rivankar, the limitation wherein administration of HMB does not reduce antitumor efficacy of the chemotherapy agent relative to administration of the chemotherapy agent alone does not limit the structure of the method.
Moreover, both HMB and doxorubicin are recognized by the prior art for their anti-tumor effect. Therefore, one of ordinary skill in the art would have reasonably expected a combination of HMB and doxorubicin to show comparable or improved antitumor efficacy compared with the chemotherapy agent alone.
Therefore the invention taken as a whole is prima facie obvious.
Response to Applicant’s arguments: With respect to the previous rejection of independent claim 1, Applicant argues that Ajouz does not teach that HMB may be administered during chemotherapy without reducing antitumor efficacy (Applicant’s remarks, p. 6).
Applicant’s remarks have been fully considered but they are not found persuasive. In this instance, Nunes teaches the antitumor effect of HMB and Rivankar teaches the antitumor effect of doxorubicin. Because each are recognized by the prior art for the same purpose, one of ordinary skill in the art would have considered administering them in combination for treating tumors, because a combination may be more effective than either HMB or doxorubicin alone. In this instance, because each are recognized by the prior art for the same effect, one of ordinary skill in the art would expect activity from the combination of HMB and doxorubicin to be greater than or comparable to the chemotherapy alone, absent evidence to the contrary.
Accordingly, for the reasons described above, the present rejection of claims 1-3 and 5 as unpatentable over Nunes in view of Rivankar is maintained.
Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Nunes (Nunes, E. A.; et al. Nutrition Research 2008, vol. 28, pp. 487-493; cited in previous office action) in view of Rivankar (Rivankar, S. Journal of Cancer Research and Therapeutics 2014, vol., 10, pp. 853-858; cited in previous office action) as applied to claims 1-3 and 5 above, and further in view of Ajouz (Ajouz, H.; et al. Journal of Nutritional Oncology 2019, vol. 4, no. 1, pp. 1-8; cited in IDS received December 15, 2022).
Nunes and Rivankar teach as described in the above rejection under 35 U.S.C. 103.
Nunes and Rivankar do not teach HMB in the free acid form, as required by claim 4.
Ajouz teaches as described in the above rejections under 35 U.S.C. 103.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the present application to substitute the HMB calcium salt taught by Nunes for HMB in the form of a free acid gel. One of ordinary skill in the art would have been motivated to substitute the HMB calcium salt for HMB in the form of a free acid gel because Nunes teaches the anti-tumor activity of HMB, and because Ajouz teaches that HMB in the form of a free acid gel presents quicker and greater plasma concentrations than HMB calcium gelatin capsules. Thus one of ordinary skill in the art would have considered the free acid formulation of HMB taught by Ajouz because of its potentially advantageous pharmacokinetic properties. In this instance, the rationale “simple substitution of one known element for another to obtain predictable results” would apply. In view of Ajouz, one of ordinary skill in the art would have recognized that the free acid form of HMB may be administered for the purposes of inhibiting tumor growth and may replace the HMB calcium salt taught by Nunes with a reasonable expectation that the HMB free acid form will also inhibit tumor growth.
Therefore the invention taken as a whole is prima facie obvious.
Response to Applicant’s arguments concerning unexpected results: Applicant further argues the experimental data in the present application demonstrate unexpected results arising from administration of HMB during chemotherapy treatment. Applicant states that as shown in Figure IA, administration of HMB in combination with doxorubicin does not reduce antitumor efficacy, as tumor growth inhibition in the Doxo+HMB group is comparable to doxorubicin alone. However, Figure lB demonstrates a substantial and unexpected increase in survival in animals receiving HMB in combination with chemotherapy. Further, Figure 2 shows a marked shift in tumor cell death toward apoptosis rather than necrosis in the Doxo+HMB group, indicating a mechanistically distinct and non-predictable interaction between HMB and chemotherapy. In addition, Figures 3 and 4 demonstrate preservation of lean body mass and significant reductions in systemic and muscle-specific inflammatory markers during chemotherapy treatment. Collectively, these results establish that administration of HMB during chemotherapy produces non-additive, synergistic biological effects that are neither taught nor suggested by the cited art and would not have been reasonably expected by one of ordinary skill in the art (Applicant’s remarks, pp. 7-8).
Applicant’s arguments regarding unexpected results have been fully considered but are not found persuasive. The examiner maintains that these effects would have been predictable in view of the prior art of record recited above. For example, May provides that cancer cachexia has been cited as the most frequent cause of morbidity and mortality in patients with cancer, and that maintenance of lean body mass above the defined critical malnutrition thresholds could enhance patient survival. Therefore, treatments that reduce or counteract cachexia in patients receiving chemotherapy would reasonably be expected to increase survival, because cancer cachexia contributes to morbidity and mortality in patients with cancer. Accordingly, the observation that the combination of HMB and chemotherapy improves survival in animals receiving HMB and chemotherapy and HMB would not have been unexpected in view of the prior art.
Furthermore, because May recognizes supplementation with HMB as increasing fat-free mass, and because Ajouz recognizes the anti-inflammatory activity of HMB, the preservation of lean body mass and significant reductions in systemic and muscle-specific inflammatory markers during chemotherapy treatment also would not have been unexpected in view of the prior art.
Regarding the observation that administration of HMB in combination with doxorubicin does not reduce antitumor efficacy, because each of HMB and doxorubicin are recognized by prior art as having anti-cancer activity, one of ordinary skill in the art would not have expected the combination of HMB and doxorubicin to show reduced antitumor efficacy.
Regarding the observation that shows a marked shift in tumor cell death toward apoptosis rather than necrosis in the Doxo+HMB group, it is unclear how this observation relates to the subject matter of the claimed invention. The claims are drawn to a method for inhibiting tumor growth, a method for increasing survival of an animal undergoing chemotherapy, a method for protecting against chemotherapy induced weight loss induced by the administration of a chemotherapy agent, a method for protecting against chemotherapy-induced inflammation in an animal undergoing chemotherapy treatment, and a method for providing an anti-cachectic treatment against weight loss induced by administration of a chemotherapy agent. The claims do not require a specific type of tumor cell death. In addition, even if the claims were to recite such a limitation, it is not clear why this effect would not be present when one of ordinary skill in the art were motivated to administer a chemotherapy and HMB, as described in the above rejections.
Finally, Applicant claims the results described above are unpredictable or superior, but fails to demonstrate this unpredictability or superiority by comparison to prior art that demonstrates the effect. Accordingly, Applicant’s claims of unexpected results are not found persuasive.
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 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); 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 nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual 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 www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 11-15 and 21-25 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, and 5 of U.S. Patent No. 11,406,609 (reference patent, hereinafter ‘609) in view of May and Davis.
Claim 1 of ‘609 claims a method of modulating autophagy in a person in need thereof comprising administering to the person from about 0.5 g to about 30 g of β-hydroxy-β-methylbutyric acid (HMB), wherein upon said administration of said HMB to the person, autophagy is modulated in adipocytes and the modulation of autophagy results in the treatment, inhibition, or reduction of an autophagy-related disease or condition selected from the list consisting of obesity, sarcopenia and sarcopenic obesity. Claim 3 of ‘609 claims HMB is selected from the group consisting of its free acid form, its salt, its ester and its lactone, and claim 5 claims the administration of HMB induces the loss of fat while maintaining or improving at least one of muscle mass, muscle strength or muscle function.
The claims of ‘609 do not claim a method for protecting against chemotherapy induced weight loss induced by the administration of a chemotherapy agent in an animal undergoing
chemotherapy treatment or a method for providing an anti-cachectic treatment against
weight loss induced by administration of a chemotherapy agent in an animal undergoing
chemotherapy treatment by administering the specified dose of HMB, wherein administration of HMB attenuates chemotherapy-induced muscle proteolysis and preserves lean body mass during chemotherapy treatment, as recited in present claims 11 and 21.
May and Davis teach as described in the above rejections under 35 U.S.C. 102 and 35 U.S.C. 103.
It would therefore have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the present application to administer HMB with a chemotherapy for protecting against chemotherapy-induced weight loss or for providing an anti-cachectic treatment because ‘609 claims administering HMB for improving muscle mass, and because May teaches that HMB may be administered to patients undergoing chemotherapy for reducing weight loss and maintaining lean body mass in a patient. Therefore, in view of the claims of ‘609 and May, one of ordinary skill in the art would have recognized HMB may be administered to patients undergoing chemotherapy for the purposes of maintaining or improving muscle mass, which would be expected to protect against chemotherapy-induced weight loss and provide an anti-cachectic treatment for animals undergoing chemotherapy.
Regarding the limitation wherein administration of HMB attenuates chemotherapy-induced muscle proteolysis and preserves lean body mass during chemotherapy treatment, such an outcome would have been expected in view of May and Davis, as described in the above rejection under 35 U.S.C. § 103.
Regarding the specific form of HMB, because ‘609 claims the free acid form and May teaches the specific calcium salt form, one of ordinary skill in the art would have considered administration of both the free acid form and calcium salt form when practicing the method obvious over the claims of ‘609 and May.
Claims 6-10 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, and 5 of U.S. Patent No. 11,406,609 (reference patent, hereinafter ‘609) in view of May, Tisdale, Davis, Ajouz, and Baracos.
The claims of ‘609 claim as described in the above nonstatutory double patenting rejection.
The claims of ‘609 do not claim a method for increasing survival of an animal undergoing chemotherapy treatment comprising administering to an animal in need thereof
being treated with a chemotherapy agent from about 0.5 g to about 30 g of HMB, wherein administration of HMB mitigates chemotherapy-induced physiological stress associated with systemic catabolic response.
May, Tisdale, Davis, Ajouz, and Baracos teach as described in the above rejections under 35 U.S.C. 102 and 35 U.S.C. 103.
It would therefore have been prima facie obvious to one of ordinary skill in the art to administer HMB with a chemotherapy for increasing survival because ‘609 claims administering HMB for inhibiting sarcopenia, May teaches the value of HMB administration in patients undergoing chemotherapy for maintaining lean body mass, which may increase survival, Tisdale teaches that up to 50% of cancer patients suffer from a progressive atrophy of adipose tissue and skeletal muscle resulting in a shortened survival time, and Davis teaches that doxorubicin causes direct muscle loss. Therefore, one of ordinary skill in the art would have recognized that HMB may be administered to counteract the effect of muscle loss via doxorubicin, and that in view of the claims of ‘609, May, and Tisdale, administration of HMB to an animal undergoing treatment with doxorubicin would reasonably be expected to increase survival of said animal.
Regarding the limitation wherein administration of HMB mitigates chemotherapy-induced physiological stress associated with systemic catabolic response, because Davis, Ajouz, and Baracos provide the expectation that administration of HMB with reduce said physiological stress, as described in the above rejection under 35 U.S.C. 103, this outcome would have been expected in view of the cited prior art.
Regarding the specific form of HMB, because ‘609 claims the free acid form and May teaches the specific calcium salt form, one of ordinary skill in the art would have considered administration of both the free acid form and calcium salt form when practicing the method obvious over the claims of ‘609 in view of May and Tisdale.
Claims 16-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, and 5 of U.S. Patent No. 11,406,609 (reference patent, hereinafter ‘609) in view of May, Davis, and Ajouz.
The claims of ‘609 claim as described in the above nonstatutory double patenting rejection.
The claims of ‘609 do not claim a method for protecting against chemotherapy-induced
inflammation in an animal undergoing chemotherapy treatment comprising administering to an animal in need thereof being treated with a chemotherapy agent HMB as claimed, wherein administration of HMB attenuates chemotherapy-induced muscle proteolysis
and preserves lean body mass during chemotherapy treatment.
May, Davis, and Ajouz teach as described in the above rejection under 35 U.S.C. 102 and 35 U.S.C. 103.
It would therefore have been prima facie obvious to one of ordinary skill in the art to administer HMB with a chemotherapy for protecting against chemotherapy-induced inflammation because ‘609 claims administering HMB for inhibiting sarcopenia, May teaches that HMB may be administered to patients undergoing chemotherapy for reducing weight loss and maintaining lean body mass in a patient, Davis teaches chemotherapies that increase inflammatory cytokines, and Ajouz teaches that HMB reduces tumor growth and protects against inflammation. Therefore, in view of the claims of ‘609, May, Davis, and Ajouz, one of ordinary skill in the art would have recognized HMB may be administered to patients undergoing chemotherapy for the purposes of maintaining lean body mass and reducing cancer-related wasting, and that this administration may protect against chemotherapy-induced inflammation in animals undergoing chemotherapy.
Regarding the limitation wherein administration of HMB reduces chemotherapy-induced activation of inflammatory cytokines, because one of ordinary skill in the art would have contemplated the co-administration of chemotherapy and HMB, as described above, and because Davis teaches chemotherapies that increase inflammatory cytokines and Ajouz teaches HMB protects against inflammation, the administration of HMB would have been expected to reduce chemotherapy-induced activation of inflammatory cytokines.
Regarding the specific form of HMB, because ‘609 claims the free acid form and May teaches the specific calcium salt form, one of ordinary skill in the art would have considered administration of both the free acid form and calcium salt form when practicing the method obvious over the claims of ‘609 and May.
Claims 1-5 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, and 5 of U.S. Patent No. 11,406,609 (reference patent, hereinafter ‘609) in view of May, Nunes, Ajouz, and Rivankar.
The claims of ‘609 claim as described in the above nonstatutory double patenting rejection.
The claims of ‘609 do not claim a method for inhibiting tumor growth in an animal undergoing chemotherapy by administering the specified dose of HMB, wherein administration of HMB does not reduce antitumor efficacy of the chemotherapy agent relative to administration of the chemotherapy agent alone, as recited in claim 1.
May, Nunes, Ajouz, and Rivankar teach as described in the above rejections under 35 U.S.C. 102 and 35 U.S.C. 103.
It would therefore have been prima facie obvious to one of ordinary skill in the art to administer HMB with a chemotherapy for inhibiting tumor growth because ‘609 claims administering HMB for inhibiting sarcopenia, because May teaches that HMB may be administered to patients undergoing chemotherapy for reducing weight loss and maintaining lean body mass in a patient, and because Ajouz teaches that HMB reduces tumor growth and protects against inflammation. Therefore, in view of the claims of ‘609, May, and Ajouz, one of ordinary skill in the art would have recognized HMB may be administered to patients undergoing chemotherapy for the purposes of maintaining lean body mass and reducing cancer-related wasting. Moreover, in view oof Ajouz and Nunes teaching the antitumor effect of HMB and Rivankar teaching the anti-tumor effect of doxorubicin, one of ordinary skill in the art would have recognized this therapy has a reasonable expectation of inhibiting tumor growth.
Regarding the limitation that administration of HMB does not reduce antitumor efficacy of the chemotherapy agent relative to administration of the chemotherapy agent alone, because each of HMB and chemotherapy, such as doxorubicin, are recognized as having an anti-tumor effect, absent evidence to the contrary, one of ordinary skill in the art would have reasonably expected the combination of HMB and chemotherapy to have comparable antitumor efficacy compared with the chemotherapy alone.
Regarding the specific form of HMB, because ‘609 claims the free acid form and May teaches the specific calcium salt form, one of ordinary skill in the art would have considered administration of both the free acid form and calcium salt form when practicing the method obvious over the claims of ‘609 and May.
Claims 11-15 and 21-25 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, and 5 of U.S. Patent No. 12,220,391 (reference patent, hereinafter ‘391) in view of May and Davis.
Claim 1 of ‘391 claims a method for inhibiting or treating a disease, a condition or a disorder responsive to autophagy modulation in adipocytes comprising administering to an animal in need thereof an effective amount of a composition of β-hydroxy-β-methylbutyric acid (HMB). Claim 2 claims the effective amount of HMB is from about 0.5 grams HMB to 30 grams HMB per day, claim 3 claims the disease, condition or disorder responsive to autophagy modulation is selected from the list that includes sarcopenia, and claim 5 claims HMB is selected from the group consisting of its free acid form, its salt, its ester and its lactone.
The claims of ‘391 do not claim a method for protecting against chemotherapy-induced weight loss or for providing an anti-cachectic treatment in an animal undergoing chemotherapy by administering the specified dose of HMB, wherein administration of HMB attenuates chemotherapy-induced muscle proteolysis and preserves lean body mass during chemotherapy
treatment, as recited in present claims 11 and 21.
May and Davis teach as described in the above rejections under 35 U.S.C. 102 and 35 U.S.C. 103.
It would therefore have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the present application to administer HMB with a chemotherapy for protecting against chemotherapy-induced weight loss or for providing an anti-cachectic treatment because ‘391 claims administering HMB for treating sarcopenia, and because May teaches that HMB may be administered to patients undergoing chemotherapy for reducing weight loss and maintaining lean muscle mass in a patient. Therefore, in view of the claims of ‘391 and May, one of ordinary skill in the art would have recognized that HMB may be used to treat sarcopenia (loss of muscle mass) in patients undergoing chemotherapy, which would be expected to protect against chemotherapy-induced weight loss and to provide an anti-cachectic treatment for animals undergoing chemotherapy.
Regarding the limitation wherein administration of HMB attenuates chemotherapy-induced muscle proteolysis and preserves lean body mass during chemotherapy treatment, in view of May and Davis, such an outcome would have been expected when administering HMB for preserving lean muscle mass, as described in the above rejection under 35 U.S.C. § 103.
Regarding the specific form of HMB, because ‘609 claims the free acid form and May teaches the specific calcium salt form, one of ordinary skill in the art would have considered administration of both the free acid form and calcium salt form when practicing the method obvious over the claims of ‘609 and May.
Claims 6-10 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, and 5 of U.S. Patent No. 12,220,391 (reference patent, hereinafter ‘391) in view of May, Tisdale, Davis, Ajouz, and Baracos.
The claims of ‘391 claim as described in the above nonstatutory double patenting rejection.
The claims of ‘391 do not claim a method for increasing survival of an animal undergoing chemotherapy treatment comprising administering to an animal in need thereof
being treated with a chemotherapy agent from about 0.5 g to about 30 g of HMB, wherein administration of HMB mitigates chemotherapy-induced physiological stress associated with systemic catabolic response.
May, Tisdale, Davis, Ajouz, and Baracos teach as described in the above rejections under 35 U.S.C. 102 and 35 U.S.C. 103.
It would therefore have been prima facie obvious to one of ordinary skill in the art to administer HMB with a chemotherapy for increasing survival because ‘391 claims administering HMB for inhibiting sarcopenia, May teaches the value of HMB administration in patients undergoing chemotherapy for maintaining lean body mass, which may increase survival, Tisdale teaches that up to 50% of cancer patients suffer from a progressive atrophy of adipose tissue and skeletal muscle resulting in a shortened survival time, and Davis teaches that doxorubicin causes direct muscle loss. Therefore, one of ordinary skill in the art would have recognized that HMB may be administered to counteract the effect of muscle loss via doxorubicin, and that in view of the claims of ‘391, May, and Tisdale, administration of HMB to an animal undergoing treatment with doxorubicin would reasonably be expected to increase survival of said animal.
Regarding the limitation wherein administration of HMB mitigates chemotherapy-induced physiological stress associated with systemic catabolic response, because Davis, Ajouz, and Baracos provide the expectation that administration of HMB with reduce said physiological stress, as described in the above rejection under 35 U.S.C. 103, this outcome would have been expected in view of the cited prior art.
Regarding the specific form of HMB, because ‘391 claims the free acid form and May teaches the specific calcium salt form, one of ordinary skill in the art would have considered administration of both the free acid form and calcium salt form when practicing the method obvious over the claims of ‘391 in view of May and Tisdale.
Claims 16-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, and 5 of U.S. Patent No. 12,220,391 (reference patent, hereinafter ‘391) in view of May, Davis, and Ajouz.
The claims of ‘391 claim as described in the above nonstatutory double patenting rejection.
The claims of ‘391 do not claim a method for protecting against chemotherapy-induced
inflammation in an animal undergoing chemotherapy treatment comprising administering to an animal in need thereof being treated with a chemotherapy agent HMB as claimed, wherein administration of HMB attenuates chemotherapy-induced muscle proteolysis
and preserves lean body mass during chemotherapy treatment.
May, Davis, and Ajouz teach as described in the above rejection under 35 U.S.C. 102 and 35 U.S.C. 103.
It would therefore have been prima facie obvious to one of ordinary skill in the art to administer HMB with a chemotherapy for protecting against chemotherapy-induced inflammation because ‘391 claims administering HMB for inhibiting sarcopenia, May teaches that HMB may be administered to patients undergoing chemotherapy for reducing weight loss and maintaining lean body mass in a patient, Davis teaches chemotherapies that increase inflammatory cytokines, and Ajouz teaches that HMB reduces tumor growth and protects against inflammation. Therefore, in view of the claims of ‘391, May, Davis, and Ajouz, one of ordinary skill in the art would have recognized HMB may be administered to patients undergoing chemotherapy for the purposes of maintaining lean body mass and reducing cancer-related wasting, and that treatment would reasonably protect against chemotherapy-induced inflammation in animals undergoing chemotherapy.
Regarding the limitation wherein administration of HMB reduces chemotherapy-induced activation of inflammatory cytokines, because one of ordinary skill in the art would have contemplated the co-administration of chemotherapy and HMB, as described above, and because Davis teaches chemotherapies that increase inflammatory cytokines and Ajouz teaches HMB protects against inflammation, the administration of HMB would have been expected to reduce chemotherapy-induced activation of inflammatory cytokines.
Regarding the specific form of HMB, because ‘391 claims the free acid form and May teaches the specific calcium salt form, one of ordinary skill in the art would have considered administration of both the free acid form and calcium salt form when practicing the method obvious over the claims of ‘391 and May.
Claims 1-5 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, and 5 of U.S. Patent No. 12,220,391 (reference patent, hereinafter ‘391) in view of May, Nunes, Ajouz, and Rivankar.
The claims of ‘391 claim as described in the above nonstatutory double patenting rejection.
The claims of ‘391 do not claim a method for inhibiting tumor growth in an animal undergoing chemotherapy by administering the specified dose of HMB, wherein administration of HMB does not reduce antitumor efficacy of the chemotherapy agent relative to administration of the chemotherapy agent alone, as recited in claim 1.
May, Nunes, Ajouz, and Rivankar teach as described in the above rejections under 35 U.S.C. 102 and 35 U.S.C. 103.
It would therefore have been prima facie obvious to one of ordinary skill in the art to administer HMB with a chemotherapy for inhibiting tumor growth because ‘391 claims administering HMB for inhibiting sarcopenia, because May teaches that HMB may be administered to patients undergoing chemotherapy for reducing weight loss and maintaining lean body mass in a patient, and because Ajouz teaches that HMB reduces tumor growth and protects against inflammation. Therefore, in view of the claims of ‘391, May, and Ajouz, one of ordinary skill in the art would have recognized HMB may be administered to patients undergoing chemotherapy for the purposes of maintaining lean body mass and reducing cancer-related wasting. Moreover, in view oof Ajouz and Nunes teaching the antitumor effect of HMB and Rivankar teaching the anti-tumor effect of doxorubicin, one of ordinary skill in the art would have recognized this therapy has a reasonable expectation of inhibiting tumor growth.
Regarding the limitation that administration of HMB does not reduce antitumor efficacy of the chemotherapy agent relative to administration of the chemotherapy agent alone, because each of HMB and chemotherapy, such as doxorubicin, are recognized as having an anti-tumor effect, absent evidence to the contrary, one of ordinary skill in the art would have reasonably expected the combination of HMB and chemotherapy to have comparable antitumor efficacy compared with the chemotherapy alone.
Regarding the specific form of HMB, because ‘391 claims the free acid form and May teaches the specific calcium salt form, one of ordinary skill in the art would have considered administration of both the free acid form and calcium salt form when practicing the method obvious over the claims of ‘391 and May.
Claims 11-15 and 21-25 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 11 of U.S. Patent No. 11,547,713 (reference patent, hereinafter ‘713) in view of May and Davis.
The present application and ‘713 are each assigned to Metabolic Technologies LLC.
Claim 11 of ‘713 claims a method for increasing the muscle mass of a human in need thereof, the method comprising the steps of administering to said human a synergistic composition comprising a combination of from about 0.5 g to about 30 g of β-hydroxy-β-methylbutyrate in the free acid form (HMB-acid) and Vitamin D in an amount sufficient to raise blood levels of Vitamin D to at least 30 ng/ml, wherein upon said administration of said synergistic combination of HMB and Vitamin D to the human said muscle mass is increased.
The claims of ‘713 do not claim a method for protecting against chemotherapy-induced weight loss or for providing an anti-cachectic treatment in an animal undergoing chemotherapy by administering the specified dose of HMB, wherein administration of HMB attenuates chemotherapy-induced muscle proteolysis and preserves lean body mass during chemotherapy
treatment, as recited in present claims 11 and 21.
May and Davis teach as described in the above rejections under 35 U.S.C. 102 and 35 U.S.C. 103.
It would therefore have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the present application to administer HMB with a chemotherapy for protecting against chemotherapy-induced weight loss or for providing an anti-cachectic treatment because ‘713 claims administering HMB for increasing the muscle mass of a human, and because May teaches that HMB may be administered to patients undergoing chemotherapy for reducing weight loss and maintaining lean muscle mass in a patient. Therefore, in view of the claims of ‘713 and May, one of ordinary skill in the art would have recognized HMB may be used to protect against chemotherapy-induced weight loss and to provide an anti-cachectic treatment in an animal undergoing chemotherapy.
Regarding the limitation wherein administration of HMB attenuates chemotherapy-induced muscle proteolysis and preserves lean body mass during chemotherapy treatment, in view of May and Davis, such an outcome would have been expected when administering HMB for preserving lean muscle mass, as described in the above rejection under 35 U.S.C. § 103.
Regarding the specific form of HMB, because ‘713 claims the free acid form and May teaches the specific calcium salt form, one of ordinary skill in the art would have considered administration of both the free acid form and calcium salt form when practicing the method obvious over the claims of ‘713 and May.
Claims 6-10 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 11 of U.S. Patent No. 11,547,713 (reference patent, hereinafter ‘713) in view of May, Tisdale, Davis, Ajouz, and Baracos.
The claims of ‘713 claim as described in the above nonstatutory double patenting rejection.
The claims of ‘713 do not claim a method for increasing survival of an animal undergoing chemotherapy treatment comprising administering to an animal in need thereof
being treated with a chemotherapy agent from about 0.5 g to about 30 g of HMB, wherein administration of HMB mitigates chemotherapy-induced physiological stress associated with systemic catabolic response.
May, Tisdale, Davis, Ajouz, and Baracos teach as described in the above rejections under 35 U.S.C. 102 and 35 U.S.C. 103.
It would therefore have been prima facie obvious to one of ordinary skill in the art to administer HMB with a chemotherapy for increasing survival because ‘713 claims administering HMB for increasing the muscle mass of a human, May teaches the value of HMB administration in patients undergoing chemotherapy for maintaining lean body mass, which may increase survival, Tisdale teaches that up to 50% of cancer patients suffer from a progressive atrophy of adipose tissue and skeletal muscle resulting in a shortened survival time, and Davis teaches that doxorubicin causes direct muscle loss. Therefore, one of ordinary skill in the art would have recognized that HMB may be administered to counteract the effect of muscle loss via doxorubicin, and that in view of the claims of ‘713, May, and Tisdale, administration of HMB to an animal undergoing treatment with doxorubicin would reasonably be expected to increase survival of said animal.
Regarding the limitation wherein administration of HMB mitigates chemotherapy-induced physiological stress associated with systemic catabolic response, because Davis, Ajouz, and Baracos provide the expectation that administration of HMB with reduce said physiological stress, as described in the above rejection under 35 U.S.C. 103, this outcome would have been expected in view of the cited prior art.
Regarding the specific form of HMB, because ‘713 claims the free acid form and May teaches the specific calcium salt form, one of ordinary skill in the art would have considered administration of both the free acid form and calcium salt form when practicing the method obvious over the claims of ‘713 in view of May and Tisdale.
Claims 16-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 11 of U.S. Patent No. 11,547,713 (reference patent, hereinafter ‘713) in view of May, Davis, and Ajouz.
The claims of ‘713 claim as described in the above nonstatutory double patenting rejection.
The claims of ‘713 do not claim a method for protecting against chemotherapy-induced
inflammation in an animal undergoing chemotherapy treatment comprising administering to an animal in need thereof being treated with a chemotherapy agent HMB as claimed, wherein administration of HMB attenuates chemotherapy-induced muscle proteolysis
and preserves lean body mass during chemotherapy treatment.
May, Davis, and Ajouz teach as described in the above rejection under 35 U.S.C. 102 and 35 U.S.C. 103.
It would therefore have been prima facie obvious to one of ordinary skill in the art to administer HMB with a chemotherapy for protecting against chemotherapy-induced inflammation because ‘713 claims administering HMB for increasing muscle mass, May teaches that HMB may be administered to patients undergoing chemotherapy for reducing weight loss and maintaining lean body mass in a patient, Davis teaches chemotherapies that increase inflammatory cytokines, and Ajouz teaches that HMB reduces tumor growth and protects against inflammation. Therefore, in view of the claims of ‘713, May, Davis, and Ajouz, one of ordinary skill in the art would have recognized HMB may be administered to patients undergoing chemotherapy for the purposes of maintaining lean body mass and reducing cancer-related wasting, and that said protect against chemotherapy-induced inflammation in animals undergoing chemotherapy.
Regarding the limitation wherein administration of HMB reduces chemotherapy-induced activation of inflammatory cytokines, because one of ordinary skill in the art would have contemplated the co-administration of chemotherapy and HMB, as described above, and because Davis teaches chemotherapies that increase inflammatory cytokines and Ajouz teaches HMB protects against inflammation, the administration of HMB would have been expected to reduce chemotherapy-induced activation of inflammatory cytokines.
Regarding the specific form of HMB, because ‘713 claims the free acid form and May teaches the specific calcium salt form, one of ordinary skill in the art would have considered administration of both the free acid form and calcium salt form when practicing the method obvious over the claims of ‘713 and May.
Claims 1-5 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 11 of U.S. Patent No. 11,547,713 (reference patent, hereinafter ‘713) in view of May, Nunes, Ajouz, and Rivankar.
The claims of ‘713 claim as described in the above nonstatutory double patenting rejection.
The claims of ‘713 do not claim a method for inhibiting tumor growth in an animal undergoing chemotherapy by administering the specified dose of HMB, wherein administration of HMB does not reduce antitumor efficacy of the chemotherapy agent relative to administration of the chemotherapy agent alone, as recited in claim 1.
May, Nunes, Ajouz, and Rivankar teach as described in the above rejections under 35 U.S.C. 102 and 35 U.S.C. 103.
It would therefore have been prima facie obvious to one of ordinary skill in the art to administer HMB with a chemotherapy for inhibiting tumor growth because ‘713 claims administering HMB for increasing muscle mass, because May teaches that HMB may be administered to patients undergoing chemotherapy for reducing weight loss and maintaining lean body mass in a patient, and because Ajouz teaches that HMB reduces tumor growth and protects against inflammation. Therefore, in view of the claims of ‘713, May, and Ajouz, one of ordinary skill in the art would have recognized HMB may be administered to patients undergoing chemotherapy for the purposes of maintaining lean body mass and reducing cancer-related wasting. Moreover, in view of Ajouz and Nunes teaching the antitumor effect of HMB and Rivankar teaching the anti-tumor effect of doxorubicin, one of ordinary skill in the art would have recognized this therapy has a reasonable expectation of inhibiting tumor growth.
Regarding the limitation that administration of HMB does not reduce antitumor efficacy of the chemotherapy agent relative to administration of the chemotherapy agent alone, because each of HMB and chemotherapy, such as doxorubicin, are recognized as having an anti-tumor effect, absent evidence to the contrary, one of ordinary skill in the art would have reasonably expected the combination of HMB and chemotherapy to have comparable antitumor efficacy compared with the chemotherapy alone.
Regarding the specific form of HMB, because ‘713 claims the free acid form and May teaches the specific calcium salt form, one of ordinary skill in the art would have considered administration of both the free acid form and calcium salt form when practicing the method obvious over the claims of ‘713 and May.
Claims 11-15 and 21-25 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 9-11 of co-pending U.S. patent application 18/095314 (reference application, hereinafter ‘314) in view of May and Davis.
The present application and ‘314 are each assigned to Metabolic Technologies LLC.
The claims received January 10, 2023 are cited in this provisional non-statutory double patenting rejection.
Claim 9 of ‘314 claims a method for increasing muscle mass in a non-human animal, the method comprising the steps of administering to said animal a composition comprising a combination of from about 10 mg/kg body weight to about 200 mg/kg body weight β-hydroxy-β-methylbutyrate (HMB) and Vitamin D in an amount sufficient to raise blood levels of Vitamin D to at least 25 ng/ml, wherein upon said administration of said combination of HMB and Vitamin D to the animal, said muscle mass is increased. Claim 10 specifies said HMB is selected from the group consisting of its free acid form, its salt, its ester and its lactone, and claim 11 specifies said HMB is a calcium salt.
The claims of ‘314 do not claim a method for protecting against chemotherapy-induced weight loss or for providing an anti-cachectic treatment in an animal undergoing chemotherapy by administering the specified dose of HMB, wherein administration of HMB attenuates chemotherapy-induced muscle proteolysis and preserves lean body mass during chemotherapy
treatment, as recited in present claims 11 and 21.
May and Davis teach as described in the above rejection under 35 U.S.C. 102 and 35 U.S.C. 103.
It would therefore have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the present application to administer HMB with a chemotherapy for protecting against chemotherapy-induced weight loss or for providing an anti-cachectic treatment because ‘314 claims administering HMB for increasing the muscle mass of a human, and because May teaches that HMB may be administered to patients undergoing chemotherapy for reducing weight loss and maintaining lean muscle mass in a patient. Therefore, in view of the claims of ‘314 and May, one of ordinary skill in the art would have recognized HMB may be used to protect against chemotherapy-induced weight loss and to provide an anti-cachectic treatment in an animal undergoing chemotherapy. Regarding claims 15 and 25, because Davis teaches the proteolytic effects of doxorubicin, one of ordinary skill in the art would have reasonably administered HMB with doxorubicin for protecting against chemotherapy-induced weight loss and providing an anti-cachectic treatment.
Regarding the limitation wherein administration of HMB attenuates chemotherapy-induced muscle proteolysis and preserves lean body mass during chemotherapy treatment, in view of May and Davis, such an outcome would have been expected when administering HMB for preserving lean muscle mass, as described in the above rejection under 35 U.S.C. § 103.
Regarding the specific form of HMB, because ‘314 claims the free acid form and the calcium salt form, one of ordinary skill in the art would have considered administration of both the free acid form and calcium salt form when practicing the method obvious over the claims of ‘314, May, and Davis.
This is a provisional non-statutory double patenting rejection because the patentably indistinct claims have not been patented.
Claims 6-10 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 9-11 of co-pending U.S. patent application 18/095314 (reference application, hereinafter ‘314) in view of May, Tisdale, Davis, Ajouz, and Baracos.
The claims of ‘314 claim as described in the above nonstatutory double patenting rejection.
The claims of ‘314 do not claim a method for increasing survival of an animal undergoing chemotherapy treatment comprising administering to an animal in need thereof
being treated with a chemotherapy agent from about 0.5 g to about 30 g of HMB, wherein administration of HMB mitigates chemotherapy-induced physiological stress associated with systemic catabolic response.
May, Tisdale, Davis, Ajouz, and Baracos teach as described in the above rejections under 35 U.S.C. 102 and 35 U.S.C. 103.
It would therefore have been prima facie obvious to one of ordinary skill in the art to administer HMB with a chemotherapy for increasing survival because ‘314 claims administering HMB for increasing muscle mass, May teaches the value of HMB administration in patients undergoing chemotherapy for maintaining lean body mass, which may increase survival, Tisdale teaches that up to 50% of cancer patients suffer from a progressive atrophy of adipose tissue and skeletal muscle resulting in a shortened survival time, and Davis teaches that doxorubicin causes direct muscle loss. Therefore, one of ordinary skill in the art would have recognized that HMB may be administered to counteract the effect of muscle loss via doxorubicin, and that in view of the claims of ‘314, May, and Tisdale, administration of HMB to an animal undergoing treatment with doxorubicin would reasonably be expected to increase survival of said animal.
Regarding the limitation wherein administration of HMB mitigates chemotherapy-induced physiological stress associated with systemic catabolic response, because Davis, Ajouz, and Baracos provide the expectation that administration of HMB with reduce said physiological stress, as described in the above rejection under 35 U.S.C. 103, this outcome would have been expected in view of the cited prior art.
Regarding the specific form of HMB, because ‘314 claims the free acid form and May teaches the specific calcium salt form, one of ordinary skill in the art would have considered administration of both the free acid form and calcium salt form when practicing the method obvious over the claims of ‘314 in view of May and Tisdale.
This is a provisional non-statutory double patenting rejection because the patentably indistinct claims have not been patented.
Claims 16-20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 9-11 of co-pending U.S. patent application 18/095314 (reference application, hereinafter ‘314) in view of May, Davis, and Ajouz.
The claims of ‘314 claim as described in the above nonstatutory double patenting rejection.
The claims of ‘314 do not claim a method for protecting against chemotherapy-induced
inflammation in an animal undergoing chemotherapy treatment comprising administering to an animal in need thereof being treated with a chemotherapy agent HMB as claimed, wherein administration of HMB attenuates chemotherapy-induced muscle proteolysis
and preserves lean body mass during chemotherapy treatment.
May, Davis, and Ajouz teach as described in the above rejection under 35 U.S.C. 102 and 35 U.S.C. 103.
It would therefore have been prima facie obvious to one of ordinary skill in the art to administer HMB with a chemotherapy for protecting against chemotherapy-induced inflammation because ‘314 claims administering HMB for increasing muscle mass, May teaches that HMB may be administered to patients undergoing chemotherapy for reducing weight loss and maintaining lean body mass in a patient, Davis teaches chemotherapies that increase inflammatory cytokines, and Ajouz teaches that HMB reduces tumor growth and protects against inflammation. Therefore, in view of the claims of ‘314, May, Davis, and Ajouz, one of ordinary skill in the art would have recognized HMB may be administered to patients undergoing chemotherapy for the purposes of maintaining lean body mass and reducing cancer-related wasting, and that said protect against chemotherapy-induced inflammation in animals undergoing chemotherapy.
Regarding the limitation wherein administration of HMB reduces chemotherapy-induced activation of inflammatory cytokines, because one of ordinary skill in the art would have contemplated the co-administration of chemotherapy and HMB, as described above, and because Davis teaches chemotherapies that increase inflammatory cytokines and Ajouz teaches HMB protects against inflammation, the administration of HMB would have been expected to reduce chemotherapy-induced activation of inflammatory cytokines.
Regarding the specific form of HMB, because ‘314 claims the free acid form and May teaches the specific calcium salt form, one of ordinary skill in the art would have considered administration of both the free acid form and calcium salt form when practicing the method obvious over the claims of ‘314 and May.
This is a provisional non-statutory double patenting rejection because the patentably indistinct claims have not been patented.
Claims 1-5 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 9-11 of co-pending U.S. patent application 18/095314 (reference application, hereinafter ‘314) in view of May, Nunes, Ajouz, and Rivankar.
The claims of ‘314 claim as described in the above nonstatutory double patenting rejection.
The claims of ‘314 do not claim a method for inhibiting tumor growth in an animal undergoing chemotherapy by administering the specified dose of HMB, wherein administration of HMB does not reduce antitumor efficacy of the chemotherapy agent relative to administration of the chemotherapy agent alone, as recited in claim 1.
May, Nunes, Ajouz, and Rivankar teach as described in the above rejections under 35 U.S.C. 102 and 35 U.S.C. 103.
It would therefore have been prima facie obvious to one of ordinary skill in the art to administer HMB with a chemotherapy for inhibiting tumor growth because ‘314 claims administering HMB for increasing muscle mass, because May teaches that HMB may be administered to patients undergoing chemotherapy for reducing weight loss and maintaining lean body mass in a patient, and because Ajouz teaches that HMB reduces tumor growth and protects against inflammation. Therefore, in view of the claims of ‘314, May, and Ajouz, one of ordinary skill in the art would have recognized HMB may be administered to patients undergoing chemotherapy for the purposes of maintaining lean body mass and reducing cancer-related wasting. Moreover, in view of Ajouz and Nunes teaching the antitumor effect of HMB and Rivankar teaching the anti-tumor effect of doxorubicin, one of ordinary skill in the art would have recognized this therapy has a reasonable expectation of inhibiting tumor growth.
Regarding the limitation that administration of HMB does not reduce antitumor efficacy of the chemotherapy agent relative to administration of the chemotherapy agent alone, because each of HMB and chemotherapy, such as doxorubicin, are recognized as having an anti-tumor effect, absent evidence to the contrary, one of ordinary skill in the art would have reasonably expected the combination of HMB and chemotherapy to have comparable antitumor efficacy compared with the chemotherapy alone.
Regarding the specific form of HMB, because ‘314 claims the free acid form and May teaches the specific calcium salt form, one of ordinary skill in the art would have considered administration of both the free acid form and calcium salt form when practicing the method obvious over the claims of ‘314 and May.
This is a provisional non-statutory double patenting rejection because the patentably indistinct claims have not been patented.
Claims 11-15 and 21-25 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 of co-pending U.S. patent application 18/936779 (reference application, hereinafter ‘779) in view of May and Davis.
The present application and ‘779 are each assigned to Metabolic Technologies LLC.
The claims received November 4, 2024 are cited in this provisional non-statutory double patenting rejection.
Claim 1 of ‘779 claims a method of inducing fat loss by increasing intracellular lipolysis while enhancing lean mass in a human in need thereof, comprising administering the human a composition of from about 0.5 g to about 30 g of β-hydroxy-β-methylbutyric acid (HMB), thereby inducing fat loss by increasing intracellular lipolysis while enhancing lean mass. Claim 2 requires said HMB is selected from the group consisting of its free acid form, its salt, its ester, and its lactone, and claim 3 requires said salt is selected from the group consisting of a sodium salt, a potassium salt, a magnesium salt, a chromium salt and a calcium salt.
The claims of ‘779 do not claim a method for protecting against chemotherapy-induced weight loss or for providing an anti-cachectic treatment in an animal undergoing chemotherapy by administering the specified dose of HMB, as recited in claims 11 and 21, wherein administration of HMB attenuates chemotherapy-induced muscle proteolysis and preserves lean body mass during chemotherapy treatment, as recited in present claims 11 and 21.
May and Davis teach as described in the above rejections under 35 U.S.C. 102 and 35 U.S.C. 103.
It would therefore have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the present application to administer HMB to an animal undergoing chemotherapy for protecting against chemotherapy-induced weight loss or for providing an anti-cachectic treatment because ‘779 claims administering HMB for enhancing lean mass in a human, and because May teaches that HMB may be administered to patients undergoing chemotherapy for reducing weight loss and maintaining lean muscle mass in a patient, which may enhance patient survival. Therefore, in view of the claims of ‘779 and May, one of ordinary skill in the art would have recognized HMB may be used to protect against chemotherapy-induced weight loss and to provide an anti-cachectic treatment in an animal undergoing chemotherapy by helping to maintain lean muscle mass. Regarding claims 15 and 25, because Davis teaches the proteolytic effects of doxorubicin, one of ordinary skill in the art would have reasonably administered HMB with doxorubicin for protecting against chemotherapy-induced weight loss and providing an anti-cachectic treatment.
Regarding the limitation wherein administration of HMB attenuates chemotherapy-induced muscle proteolysis and preserves lean body mass during chemotherapy treatment, in view of May and Davis, such an outcome would have been expected when administering HMB for preserving lean muscle mass, as described in the above rejection under 35 U.S.C. § 103.
Regarding the specific form of HMB, because ‘779 claims the free acid form and the calcium salt form, one of ordinary skill in the art would have considered administration of both the free acid form and calcium salt form when practicing the method obvious over the claims of ‘779 and May.
This is a provisional non-statutory double patenting rejection because the patentably indistinct claims have not been patented.
Claims 6-10 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 of co-pending U.S. patent application 18/936779 (reference application, hereinafter ‘779) in view of May, Tisdale, Davis, Ajouz, and Baracos.
The claims of ‘779 claim as described in the above nonstatutory double patenting rejection.
The claims of ‘779 do not claim a method for increasing survival of an animal undergoing chemotherapy treatment comprising administering to an animal in need thereof
being treated with a chemotherapy agent from about 0.5 g to about 30 g of HMB, wherein administration of HMB mitigates chemotherapy-induced physiological stress associated with systemic catabolic response.
May, Tisdale, Davis, Ajouz, and Baracos teach as described in the above rejections under 35 U.S.C. 102 and 35 U.S.C. 103.
It would therefore have been prima facie obvious to one of ordinary skill in the art to administer HMB with a chemotherapy for increasing survival because ‘779 claims administering HMB for enhancing lean mass, May teaches the value of HMB administration in patients undergoing chemotherapy for maintaining lean body mass, which may increase survival, Tisdale teaches that up to 50% of cancer patients suffer from a progressive atrophy of adipose tissue and skeletal muscle resulting in a shortened survival time, and Davis teaches that doxorubicin causes direct muscle loss. Therefore, one of ordinary skill in the art would have recognized that HMB may be administered to counteract the effect of muscle loss via doxorubicin, and that in view of the claims of ‘779, May, and Tisdale, administration of HMB to an animal undergoing treatment with doxorubicin would reasonably be expected to increase survival of said animal.
Regarding the limitation wherein administration of HMB mitigates chemotherapy-induced physiological stress associated with systemic catabolic response, because Davis, Ajouz, and Baracos provide the expectation that administration of HMB with reduce said physiological stress, as described in the above rejection under 35 U.S.C. 103, this outcome would have been expected in view of the cited prior art.
Regarding the specific form of HMB, because ‘779 claims the free acid form and May teaches the specific calcium salt form, one of ordinary skill in the art would have considered administration of both the free acid form and calcium salt form when practicing the method obvious over the claims of ‘779 in view of May and Tisdale.
This is a provisional non-statutory double patenting rejection because the patentably indistinct claims have not been patented.
Claims 16-20 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 of co-pending U.S. patent application 18/936779 (reference application, hereinafter ‘779) in view of May, Davis, and Ajouz.
The claims of ‘779 claim as described in the above nonstatutory double patenting rejection.
The claims of ‘779 do not claim a method for protecting against chemotherapy-induced
inflammation in an animal undergoing chemotherapy treatment comprising administering to an animal in need thereof being treated with a chemotherapy agent HMB as claimed, wherein administration of HMB attenuates chemotherapy-induced muscle proteolysis
and preserves lean body mass during chemotherapy treatment.
May, Davis, and Ajouz teach as described in the above rejection under 35 U.S.C. 102 and 35 U.S.C. 103.
It would therefore have been prima facie obvious to one of ordinary skill in the art to administer HMB with a chemotherapy for protecting against chemotherapy-induced inflammation because ‘779 claims administering HMB for enhancing lean mass, May teaches that HMB may be administered to patients undergoing chemotherapy for reducing weight loss and maintaining lean body mass in a patient, Davis teaches chemotherapies that increase inflammatory cytokines, and Ajouz teaches that HMB reduces tumor growth and protects against inflammation. Therefore, in view of the claims of ‘779, May, Davis, and Ajouz, one of ordinary skill in the art would have recognized HMB may be administered to patients undergoing chemotherapy for the purposes of maintaining lean body mass and reducing cancer-related wasting, and that said protect against chemotherapy-induced inflammation in animals undergoing chemotherapy.
Regarding the limitation wherein administration of HMB reduces chemotherapy-induced activation of inflammatory cytokines, because one of ordinary skill in the art would have contemplated the co-administration of chemotherapy and HMB, as described above, and because Davis teaches chemotherapies that increase inflammatory cytokines and Ajouz teaches HMB protects against inflammation, the administration of HMB would have been expected to reduce chemotherapy-induced activation of inflammatory cytokines.
Regarding the specific form of HMB, because ‘779 claims the free acid form and May teaches the specific calcium salt form, one of ordinary skill in the art would have considered administration of both the free acid form and calcium salt form when practicing the method obvious over the claims of ‘779 and May.
This is a provisional non-statutory double patenting rejection because the patentably indistinct claims have not been patented.
Claims 1-5 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 of co-pending U.S. patent application 18/936779 (reference application, hereinafter ‘779) in view of May, Nunes, Ajouz, and Rivankar.
The claims of ‘779 claim as described in the above nonstatutory double patenting rejection.
The claims of ‘779 do not claim a method for inhibiting tumor growth in an animal undergoing chemotherapy by administering the specified dose of HMB, wherein administration of HMB does not reduce antitumor efficacy of the chemotherapy agent relative to administration of the chemotherapy agent alone, as recited in claim 1.
May, Nunes, Ajouz, and Rivankar teach as described in the above rejections under 35 U.S.C. 102 and 35 U.S.C. 103.
It would therefore have been prima facie obvious to one of ordinary skill in the art to administer HMB with a chemotherapy for inhibiting tumor growth because ‘779 claims administering HMB for enhancing lean mass, because May teaches that HMB may be administered to patients undergoing chemotherapy for reducing weight loss and maintaining lean body mass in a patient, and because Ajouz teaches that HMB reduces tumor growth and protects against inflammation. Therefore, in view of the claims of ‘779, May, and Ajouz, one of ordinary skill in the art would have recognized HMB may be administered to patients undergoing chemotherapy for the purposes of maintaining lean body mass and reducing cancer-related wasting. Moreover, in view of Ajouz and Nunes teaching the antitumor effect of HMB and Rivankar teaching the anti-tumor effect of doxorubicin, one of ordinary skill in the art would have recognized this therapy has a reasonable expectation of inhibiting tumor growth.
Regarding the limitation that administration of HMB does not reduce antitumor efficacy of the chemotherapy agent relative to administration of the chemotherapy agent alone, because each of HMB and chemotherapy, such as doxorubicin, are recognized as having an anti-tumor effect, absent evidence to the contrary, one of ordinary skill in the art would have reasonably expected the combination of HMB and chemotherapy to have comparable antitumor efficacy compared with the chemotherapy alone.
Regarding the specific form of HMB, because ‘779 claims the free acid form and May teaches the specific calcium salt form, one of ordinary skill in the art would have considered administration of both the free acid form and calcium salt form when practicing the method obvious over the claims of ‘779 and May.
This is a provisional non-statutory double patenting rejection because the patentably indistinct claims have not been patented.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
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/B.M.B./ Examiner, Art Unit 1693
/ANDREA OLSON/ Primary Examiner, Art Unit 1693
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