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
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statement (IDS) was submitted on 9/11/2023, before the mailing of a first office action. The submissions are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Status
Claims 16-33, filed 9/11/2023, are pending. Claims 16-33 are under examination.
Specification
The use of the term “FastPrep-24” on page 13, line 39 of the specification, which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
The use of the term “Chemidoc” on page 14, line 2 of the specification, which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
The use of the term “SPSS Statistics” on page 14, line 11 of the specification, which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Objections
Claim 16 is objected to because of the following informalities. Claim 16 recites the phrase “…comprising administering tot the human subject…”. In this context, “tot” should likely be “to”. Appropriate correction is required.
Claim 16 is objected to because of the following informalities. Claim 16 recites the phrase “A method for preventing and/or treating of whole body protein metabolism decline…”. In this context, “of” should be removed. Appropriate correction is required.
Claim Interpretation
Claim 16 recites the terms “whole body protein metabolism”, “whole body protein decline”, “whole body protein metabolism”, and “whole body protein function”. These terms are not specifically defined, and therefore will be interpreted in light of the specification and available prior art with the broadest reasonable interpretation.
The specification discusses protein atrophy during hospitalizations and rehabilitations: “On average, patients undergoing for instance a knee or hip replacement, are in the
hospital for 1-3 days post-surgery. There is often an additional period of muscle disuse ranging from 7-21 days before the patient can begin physical therapy rehabilitation to restore function in the operative limb. All that time that a load-bearing extremity is not used, it sets in motion a series of metabolic processes that lead to muscle atrophy resulting in loss of muscle strength and muscle mass.” (Specification, page 1, line 15).
Furthermore, the prior art also discusses this issue:
“Protein loss, manifested as a reduction in skeletal muscle mass and total body nitrogen content, is observed universally in all critically ill patients. Protein catabolism is part of the metabolic response to critical illness. The magnitude of protein loss is associated with increased morbidity and mortality.1 The depletion of muscle mass seen clinically has been associated with impaired function and poor clinical outcomes.1,2 Adequate protein delivery to hospitalized and critically ill patients is very likely essential for optimal nutrition therapy, but high-quality evidence from clinical trials supporting this view is currently lacking.” (Hurt et al., page 143S, col. 1, para. 2).
Hurt also discloses that critical illnesses can lead to other protein-related issues: “The complexity of protein kinetics is amplified in septic critically ill patients compared with non-ICU or nonseptic patients. The inflammatory and dysregulated immune responses seen in sepsis and major trauma lead to organ dysfunction and catabolic signaling. While hepatic protein synthetic rates may be normal or only minimally elevated in sepsis, total systemic degradation rates are dramatically increased.” (Hurt et al., page 144S, col. 1, para. 7).
However, other causes exist for protein metabolism problems.
Katayama (Katayama, Kazuhiro. Nutrition research 74: 1-9. (2020)) discloses: ” The capacity to metabolize proteins is closely related to the hepatic functional reserve in patients with chronic liver disease, and hypoalbuminemia and hyperammonemia develop along with hepatic disease progression. Zinc deficiency, which is frequently observed in patients with chronic liver disease, significantly affects protein metabolism. Ornithine transcarbamylase is a zinc enzyme involved in the urea cycle.” (Katayama, page 1, Abstract).
Kelly et al. (Kelly, et al. Mental retardation and developmental disabilities research reviews 7.4: 287-295. (2001)) discloses: “The clinical importance of glutamate metabolism has been highlighted by the recent discovery of a dominantly-expressed defect in glutamate metabolism, the hyperinsulinism/ hypermmonemia syndrome (HI/HA) [Weinzimer et al., 1997; Stanley et al., 1998; 2000]. Defects in glutamate metabolism have been implicated in other disorders as well, but these associations are less well established. This paper briefly reviews the pathways of glutamate metabolism and discusses the HI/HA syndrome and other potential disorders of glutamate metabolism.” (Kelly et al., page 287, col. 1, para. 1).
Consequently, the terms “whole body protein metabolism”, “whole body protein decline”, “whole body protein metabolism”, and “whole body protein function” shall be interpreted to refer to muscle loss and muscle gain, protein synthesis problems associated with medical intervention and rehabilitation, as well as genetic disorders that affect protein synthesis.
Regarding claim 17, claim 17 is interpreted to refer to the proteins (a)-(d) from claim 16 based off the references to these proteins found throughout the specification.
Regarding claim 20, claim 20 is interpreted to refer to the proteins (a)-(d) from claim 19 based off the references to these proteins found throughout the specification.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 17, 20, and 26 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding claim 17, claim 17 recites the limitation wherein the sum of said proteins equals 100 weight% of the protein fraction. Because claim 16 uses the “comprising” transition phrase, other proteins may be present in the composition referenced by claim 16. Consequently, it is not clear exactly which proteins are being referenced by the phrase “said proteins” in claim 17. Amendment to refer to “the sum of proteins (a)-(d)” would remedy this lack of clarity. Claim 17 is rejected.
Regarding claim 20, claim 20 recites the limitation wherein the sum of said proteins equals 100 weight% of the protein fraction. Because claim 19 uses the “comprising” transition phrase, other proteins may be present in the composition referenced by claim 19. Consequently, it is not clear exactly which proteins are being referenced by the phrase “said proteins” in claim 19. Amendment to refer to “the sum of proteins (a)-(d)” would remedy this lack of clarity. Claim 19 is rejected.
Regarding claim 26, claim 26 recites the limitation "improving muscle function" in line 1. There is insufficient antecedent basis for this limitation in the claim. Furthermore, the term “involves” does not clearly communicate the relationship between improving muscle function and improving protein synthesis. Claim 26 is rejected.
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 16-33 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for treating whole body protein metabolism decline, whole body protein function decline, or improving whole body protein metabolism, or improving whole body protein function in the case wherein said treatment addresses amino acid availability, does not reasonably provide enablement for preventing whole body protein metabolism decline or whole body protein function decline, nor treating whole body protein metabolism decline, whole body protein function decline, or improving whole body protein metabolism, or improving whole body protein function in all possible cases (causes). The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
In order to determine compliance with the enablement requirement of 35 U.S.C. 112(a), the Federal Circuit developed a framework of factors in In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), referred to as the Wands factors to assess whether any necessary experimentation required by the specification is "reasonable" or is "undue." Consistent with Amgen Inc. et al. v. Sanofi et al., 598 U.S. 594, 2023 USPQ2d 602 (2023), the Wands factors continue to provide a framework for assessing enablement in a utility application or patent, regardless of technology area. Guidelines for Assessing Enablement in Utility Applications and Patents in View of the Supreme Court Decision in Amgen Inc. et al. v. Sanofi et al., 89 FR 1563 (January 10, 2024). These factors include, but are not limited to:
The breadth of the claims;
The scope of claim 16 is broad because it encompasses so many different scenarios that result in protein function decline.
The nature of the invention;
The invention is a method for preventing and/or treating of whole body protein metabolism decline or whole body protein function decline, or improving whole body protein metabolism or whole body protein function, in a human subject suffering from starvation and/or metabolic stress following trauma, inflammation, sepsis, critical illness, stroke, cancer or COPD, comprising administering tot the human subject a liquid nutritional composition wherein the composition comprises a protein fraction comprising (a) 15 to 35 weight% of casein ;(b) 25 to 50 weight% of whey protein ;(c) 10 to 30 weight% of soy protein ; and (d) 10 to 30 weight% of pea protein ;relative to the total protein in protein fraction.
The state of the prior art;
Lack of nutrition and therefore low amino acid intake can cause protein-related problems in the case of critical illness: “Protein loss, manifested as a reduction in skeletal muscle mass and total body nitrogen content, is observed universally in all critically ill patients. Protein catabolism is part of the metabolic response to critical illness. The magnitude of protein loss is associated with increased morbidity and mortality.1 The depletion of muscle mass seen clinically has been associated with impaired function and poor clinical outcomes.1,2 Adequate protein delivery to hospitalized and critically ill patients is very likely essential for optimal nutrition therapy, but high-quality evidence from clinical trials supporting this view is currently lacking.” (Hurt et al., page 143S, col. 1, para. 2).
However, protein synthesis problems can occur for other reasons.
Katayama (Katayama, Kazuhiro. Nutrition research 74: 1-9. (2020)) discloses: ” The capacity to metabolize proteins is closely related to the hepatic functional reserve in patients with chronic liver disease, and hypoalbuminemia and hyperammonemia develop along with hepatic disease progression. Zinc deficiency, which is frequently observed in patients with chronic liver disease, significantly affects protein metabolism. Ornithine transcarbamylase is a zinc enzyme involved in the urea cycle.” (Katayama, page 1, Abstract).
Kelly et al. (Kelly, et al. Mental retardation and developmental disabilities research reviews 7.4: 287-295. (2001)) discloses: “The clinical importance of glutamate metabolism has been highlighted by the recent discovery of a dominantly-expressed defect in glutamate metabolism, the hyperinsulinism/ hypermmonemia syndrome (HI/HA) [Weinzimer et al., 1997; Stanley et al., 1998; 2000]. Defects in glutamate metabolism have been implicated in other disorders as well, but these associations are less well established. This paper briefly reviews the pathways of glutamate metabolism and discusses the HI/HA syndrome and other potential disorders of glutamate metabolism.” (Kelly et al., page 287, col. 1, para. 1).
The level of one of ordinary skill;
A person of ordinary skill in the art typically would possess at least a Master’s level education and frequently a Ph.D.
The level of predictability in the art;
While it is predictable that starvation conditions can cause protein metabolic problems, Liu et al. characterizes the issue in the following manner: “The amino acid requirement during illness cannot be easily quantified. The World Health Organization, the Food and Agriculture Organization of the United Nations, and the United Nations University (WHO/FAO/UNU) protein report (2007) [4] for essential amino acids in healthy individuals is generally used as a reference to assess the quality of protein sources used in medical nutrition.” (Liu et al., page 1, para. 2).
(F) The amount of direction provided by the inventor and the existence of working examples and the quantity of experimentation needed to make or use the invention based on the content of the disclosure.
Applicant discloses data for muscle protein synthesis ratios in the case of mice subjected to partial starvation conditions.
Regarding claim 16, the scope of claim 16 includes the genetic causes for protein metabolic decline described above. Merely adjusting nutrition by the method of claim 16 is unlikely to treat much less prevent protein metabolic decline in these scenarios. It would require undue experimentation for a person of ordinary skill in the art to test the claimed method for efficacy for all possible metabolic decline scenarios.
Furthermore, neither the specification nor the prior art demonstrates that such a composition can prevent such protein metabolic declines from occurring. The specification and the prior art only support treatment of such a condition by improving protein synthesis.
Consequently, the specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims and claim 16 is rejected.
Regarding claims 17-21, these claims have the same scope as claim 16 in terms of condition to be treated and therefore these claims are also rejected.
Regarding claim 22, claim 22 narrows the scope of the condition to be treated to preventing and/or treating muscle decline or improving muscle function. However, muscle decline may still be caused by a genetic condition that result in glutamic acid disorders or a zinc deficiency as described above.
Furthermore, neither the specification nor the prior art demonstrates that such a composition can prevent such protein metabolic declines from occurring. The specification and the prior art only support treatment of such a condition by improving protein synthesis.
Consequently, the specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims and claim 22 is rejected.
Regarding claims 23-31, these claims have the same scope as claim 16 in terms of condition to be treated and therefore these claims are also rejected.
Regarding claim 32, claim 32 narrows the scope of the condition to be treated to preventing and/or treating muscle decline or improving muscle function. However, muscle decline may still be caused by a genetic condition that result in glutamic acid disorders or a zinc deficiency as described above.
Furthermore, neither the specification nor the prior art demonstrates that such a composition can prevent such protein metabolic declines from occurring. The specification and the prior art only support treatment of such a condition by improving protein synthesis.
Consequently, the specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims and claim 32 is rejected.
Regarding claim 33, this claim has the same scope as claim 32 in terms of condition to be treated and therefore these claims are also rejected.
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.
Claims 16-21, 23-25, and 29-31 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Liu et al. (Liu, et al Nutrients 11.11: 2613. (2019)) as evidenced by Hurt, et al. (Hurt, et al. Nutrition in clinical practice 32: 142S-151S (2017)).
Regarding claim 16, claim 16 recites a method for preventing and/or treating of whole body protein metabolism decline or whole body protein function decline, or improving whole body protein metabolism or whole body protein function, in a human subject suffering from starvation and/or metabolic stress following trauma, inflammation, sepsis, critical illness, stroke, cancer or COPD, comprising administering tot the human subject a liquid nutritional composition wherein the composition comprises a protein fraction comprising (a) 15 to 35 weight% of casein ;(b) 25 to 50 weight% of whey protein ;(c) 10 to 30 weight% of soy protein ; and (d) 10 to 30 weight% of pea protein ;relative to the total protein in protein fraction.
Liu discloses the following nutritional composition: ” A blend of dairy and vegetable proteins (35% whey, 25% casein, 20% soy, 20% pea; P4) developed to obtain a more balanced amino acid profile with higher chemical scores, was compared to its constituent single proteins.” (Liu et al., page 1, Abstract). These percentages read on the claimed ranges of Applicant claim 16. Liu also discloses medical applications of this composition: “Protein quality is important for patients needing medical nutrition, especially those dependent on tube feeding.” (Liu et al., page 1, Abstract).
Liu also discloses that the P4 formulation provides a balanced ratio of amino acids that is optimal for amino acid usage: “The results of this study showed substantially greater availability of leucine and methionine with P4 protein than with vegetable proteins (e.g., iAUC of leucine and methionine were ~1.5 and 2 times higher with P4 protein vs. soy). Moreover, P4 protein resulted in a statistically significant increase in arginine availability and a non-significant increase in glycine availability compared to casein and whey (e.g., iAUC arginine and glycine were ~1.4 times higher with P4 protein vs. whey protein). These data indicate that intake of P4 protein can lead to a higher plasma concentration of the limiting amino acid in the protein source compared to the other single protein sources. This finding is relevant, because higher availability of limiting amino acids could increase the efficiency of other amino acids and thus improve protein accretion.” (Liu et al., page 11, para. 2).
Regarding the composition being liquid, Liu discloses that the protein composition is liquid: “The products were prepared by blending 18g pure protein in 360 mL of water. No extra calories (i.e., fat, carbohydrate, or micronutrients) were added. Sucralose and flavors (i.e., caramel, orange, and peach) were used to improve the taste and palatability of the protein solutions. The protein solutions were sterilized and subsequently homogenized. The five products had a similar pH (around 7.1).” (Liu et al, page 4, para. 2).
Regarding the method for preventing and/or treating of whole body protein metabolism decline or whole body protein function decline, or improving whole body protein metabolism or whole body protein function, Liu discloses: “An optimal dietary protein source may be defined by its ability to provide all amino acids required for optimal protein synthesis in muscles and other organs.” (Liu et al., page 1, para. 1). Liu also discloses that “The amino acid with the lowest chemical score is defined as the first limiting amino acid. It has been hypothesized that amino acids with chemical scores higher than the limiting amino acid cannot be efficiently utilized for protein synthesis [1,2,5]; therefore, the nutritional quality of a protein source can be determined by the chemical score of the first limiting amino acid.” (Liu et al., page 1, para .2).
Regarding the subjects of the method, Liu discloses: “Eligible subjects were recruited from a healthy volunteer database, who were: (a) aged ≥ 65 years; (b) between 20 and 30 kg/m2 for body mass index; and (c) judged by the investigator to be in good health. Prior to participation in the study, we confirmed that the subjects were in a fasting state from 22:00 h the day before the study visits; were not using laxatives, antacids, anticonvulsants, prokinetics, or any medication influencing gastric acid production; were not taking nutritional supplements, with the exception of (multi) vitamin and/or mineral supplements; were not current smokers; had not consumed alcohol within the previous 24 h; and had not done any sort of intense physical activity 24 h prior to the study visits. All subjects were required to maintain normal dietary habits for the duration of the study.” (Liu et al., page 3, para. 1).
Hurt discloses how levels of amino acids can affect different protein metabolic pathways. For example, “Arginine deficiency states can occur in critically ill patients, worsening outcomes by impairing adaptive immune responses and endothelial function, among other problems. The arginine deficiency occurs generally as a result of increased destruction by the enzyme arginase.” (Hurt et al., page 144S, col. 2, para.1). Also, “Branched-chain amino acids (BCAAs), especially leucine, act as a trigger for increasing muscle protein synthesis. Leucine is an insulin secretagogue and potent activator of the mammalian target of rapamycin (mTOR) nutrient signaling pathway.” (Hurt et al., page 144S, col. 2, para. 8).
The disclosure of Hurt emphasizes the importance of the arginine and leucine availability provided by the composition of Liu discussed above. Liu discloses that the P4 formulation provides a superior set of limiting amino acids: “Our study showed that differences in the amino acid content of protein sources were reflected in differences in post-prandial individual amino acid availability. A more balanced amino acid profile in P4 protein with higher chemical scores resulted in a more balanced post-prandial amino acid availability compared to single protein sources. “ (Liu, et al., page 12, para. 1).
Finally, Hurt discloses that critical illness can cause protein metabolism decline: ““Protein loss, manifested as a reduction in skeletal muscle mass and total body nitrogen content, is observed universally in all critically ill patients. Protein catabolism is part of the metabolic response to critical illness. The magnitude of protein loss is associated with increased morbidity and mortality.1 The depletion of muscle mass seen clinically has been associated with impaired function and poor clinical outcomes.1,2 Adequate protein delivery to hospitalized and critically ill patients is very likely essential for optimal nutrition therapy, but high-quality evidence from clinical trials supporting this view is currently lacking.” (Hurt et al., page 143S, col. 1, para. 2).
Consequently, Liu et al. discloses a method of treating whole body protein metabolism decline or whole body protein function decline by providing a composition that provides a superior ratio of limiting amino acids wherein the composition also reads on the composition disclosed by Applicant.
Claim 16 is anticipated by Liu et al. as evidenced by Hurt et al. and rejected.
Regarding claim 17, claim 16 is anticipated as described above. Claim 17 further recites the case wherein the sum of said proteins equals 100wt% of the protein fraction. Liu discloses the formulation 35% whey, 25% casein, 20% soy, 20% pea, which sums to 100wt%. (Liu et al., page 1, Abstract).
Claim 17 is anticipated by Liu et al. as evidenced by Hurt et al. and rejected.
Regarding claim 18, claim 16 is anticipated as described above. Claim 18 further recites the case wherein the human subject is a human elderly subject of at least 50 years of age. Liu discloses test subjects of 65 years of age or older: ““Eligible subjects were recruited from a healthy volunteer database, who were: (a) aged ≥ 65 years; (b) between 20 and 30 kg/m2 for body mass index; and (c) judged by the investigator to be in good health.” (Liu et al., page 3, para. 1).
Claim 18 is anticipated by Liu et al. as evidenced by Hurt et al. and rejected.
Regarding claim 19, claim 16 is anticipated as described above. Claim 19 further recites the method according to claim 16, wherein the composition comprises a protein fraction comprising (a) 20 to 30 weight% of casein ;(b) 30 to 40 weight% of whey protein ;(c) 15 to 25 weight% of soy protein ; and(d) 15 to 25 weight% of pea protein ;relative to the total protein in the protein fraction.
Liu discloses the formulation 35% whey, 25% casein, 20% soy, 20% pea, which reads on these ranges. (Liu et al., page 1, Abstract).
Claim 19 is anticipated by Liu et al. as evidenced by Hurt et al. and rejected.
Regarding claim 20, claim 19 is anticipated as described above. Claim 20 further recites the case wherein the sum of said proteins equals 100wt% of the protein fraction. Liu discloses the formulation 35% whey, 25% casein, 20% soy, 20% pea, which sums to 100wt%. (Liu et al., page 1, Abstract).
Claim 20 is anticipated by Liu et al. as evidenced by Hurt et al. and rejected.
Regarding claim 21, claim 16 is anticipated as described above. Claim 21 recites:
PNG
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327
563
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Liu et al. discloses the following amino acid pattern for the P4 product:
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268
241
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231
244
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(Liu et al., page 2, Table 1).
These disclosed values read on the ranges in Applicant claim 21.
Claim 21 is anticipated by Liu et al. as evidenced by Hurt et al. and rejected.
Regarding claim 23, claim 16 is anticipated as described above. Claim 23 further recites the case wherein the proteins are in hydrolyzed or intact form.
Liu discloses that the proteins were intact for consumption: “Five products were tested: P4 protein blend (Nutricia, Utrecht, The Netherlands), casein, whey, soy, and pea. Table 1 shows the amino acid composition of the study products. The study products were food-graded produced by NIZO food research B.V, Ede, The Netherlands. The products were prepared by blending 18 g pure protein in 360 mL of water. No extra calories (i.e., fat, carbohydrate, or micronutrients) were added. Sucralose and flavors (i.e., caramel, orange, and peach) were used to improve the taste and palatability of the protein solutions. The protein solutions were sterilized and subsequently homogenized. The five products had a similar pH (around 7.1).” (Liu et al, page 4, para. 2).
Claim 23 is anticipated by Liu et al. as evidenced by Hurt et al. and rejected.
Regarding claim 24, claim 16 is anticipated as described above. Claim 24 further recites the case wherein there are no free amino acids, peptides, or hydrolysates in the composition.
Liu discloses that the proteins were intact for consumption: “Five products were tested: P4 protein blend (Nutricia, Utrecht, The Netherlands), casein, whey, soy, and pea. Table 1 shows the amino acid composition of the study products. The study products were food-graded produced by NIZO food research B.V, Ede, The Netherlands. The products were prepared by blending 18 g pure protein in 360 mL of water. No extra calories (i.e., fat, carbohydrate, or micronutrients) were added. Sucralose and flavors (i.e., caramel, orange, and peach) were used to improve the taste and palatability of the protein solutions. The protein solutions were sterilized and subsequently homogenized. The five products had a similar pH (around 7.1).” (Liu et al, page 4, para. 2).
No process was used by Liu to create free peptides or free amino acids.
Claim 24 is anticipated by Liu et al. as evidenced by Hurt et al. and rejected.
Regarding claim 25, claim 16 is anticipated as described above. Claim 25 further recites the case wherein the human subject is a human elderly subject of at least 60 years of age. Liu discloses test subjects of 65 years of age or older: ““Eligible subjects were recruited from a healthy volunteer database, who were: (a) aged ≥ 65 years; (b) between 20 and 30 kg/m2 for body mass index; and (c) judged by the investigator to be in good health.” (Liu et al., page 3, para. 1).
Claim 25 is anticipated by Liu et al. as evidenced by Hurt et al. and rejected.
Regarding claim 29, claim 16 is anticipated as described above. Claim 29 further recites the case wherein the composition is adapted for tube feeding.
Liu contemplates the case where tube feeding is required: “Protein quality is important for patients needing medical nutrition, especially those dependent on tube feeding.” (Liu et al., page 1, Abstract).
Claim 29 is anticipated by Liu et al. as evidenced by Hurt et al. and rejected.
Regarding claim 30, claim 16 is anticipated as described above. Claim 30 further recites the case wherein the amount of protein administered to the human subject is between 10 g and 30 g per serving.
Liu discloses the administration of 18g of protein per subject: “The products were prepared by blending 18g pure protein in 360 mL of water. No extra calories (i.e., fat, carbohydrate, or micronutrients) were added. Sucralose and flavors (i.e., caramel, orange, and peach) were used to improve the taste and palatability of the protein solutions. The protein solutions were sterilized and subsequently homogenized. The five products had a similar pH (around 7.1).” (Liu et al, page 4, para. 2).
Claim 30 is anticipated by Liu et al. as evidenced by Hurt et al. and rejected.
Regarding claim 31, claim 16 is anticipated as described above. Claim 30 further recites the case wherein the amount of protein administered to the human subject is between 15 g and 25 g per serving.
Liu discloses the administration of 18g of protein per subject: “The products were prepared by blending 18g pure protein in 360 mL of water. No extra calories (i.e., fat, carbohydrate, or micronutrients) were added. Sucralose and flavors (i.e., caramel, orange, and peach) were used to improve the taste and palatability of the protein solutions. The protein solutions were sterilized and subsequently homogenized. The five products had a similar pH (around 7.1).” (Liu et al, page 4, para. 2).
Claim 31 is anticipated by Liu et al. as evidenced by Hurt et al. and rejected.
Claim Rejections - 35 USC § 103
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 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.
Claims 22, 26-28, and 32-33 are rejected under 35 U.S.C. 103 as being unpatentable over Liu et al. (Liu, et al Nutrients 11.11: 2613. (2019)) as evidenced by Hurt, et al. (Hurt, et al. Nutrition in clinical practice 32: 142S-151S (2017) as applied to claim 16 above, further in view of Hurt, et al. (Hurt, et al. Nutrition in clinical practice 32: 142S-151S (2017)).
Regarding claim 22, claim 16 is anticipated as described above.
The composition of Liu delivers an optimal range of limiting amino acids: “The results of this study showed substantially greater availability of leucine and methionine with P4 protein than with vegetable proteins (e.g., iAUC of leucine and methionine were ~1.5 and 2 times higher with P4 protein vs. soy). Moreover, P4 protein resulted in a statistically significant increase in arginine availability and a non-significant increase in glycine availability compared to casein and whey (e.g., iAUC arginine and glycine were ~1.4 times higher with P4 protein vs. whey protein). These data indicate that intake of P4 protein can lead to a higher plasma concentration of the limiting amino acid in the protein source compared to the other single protein sources. This finding is relevant, because higher availability of limiting amino acids could increase the efficiency of other amino acids and thus improve protein accretion.” (Liu et al., page 11, para. 2).
Hurt discloses the importance of leucine for muscle synthesis: “Branched-chain amino acids (BCAAs), especially leucine, act as a trigger for increasing muscle protein synthesis. Leucine is an insulin secretagogue and potent activator of the mammalian target of rapamycin (mTOR) nutrient signaling pathway.” (Hurt et al., page 144S, col. 2, para. 8).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to use the composition of Liu to deliver an optimal ratio of limiting amino acids to encourage muscle synthesis as described by Hurt to arrive at the claimed invention.
A person of ordinary skill in the art would be motivated to use this method to treat muscle decline because muscle decline in hospitalized patients is unwanted: “Protein loss, manifested as a reduction in skeletal muscle mass and total body nitrogen content, is observed universally in all critically ill patients. Protein catabolism is part of the metabolic response to critical illness. The magnitude of protein loss is associated with increased morbidity and mortality.1 The depletion of muscle mass seen clinically has been associated with impaired function and poor clinical outcomes.1,2 Adequate protein delivery to hospitalized and critically ill patients is very likely essential for optimal nutrition therapy, but high-quality evidence from clinical trials supporting this view is currently lacking.” (Hurt et al., page 143S, col. 1, para. 2).
A person of ordinary skill in the art would have a reasonable expectation of success because the composition of Liu delivers an optimized amount of leucine accompanied by an optimized amount of other amino acids to complement said leucine: “This finding is relevant, because higher availability of limiting amino acids could increase the efficiency of other amino acids and thus improve protein accretion.” (Liu et al., page 11, para. 2).
Consequently, claim 22 is obvious over Liu et al. as evidenced by Hurt et al. as applied to claim 16 above, further in view of Hurt et al. and rejected.
Regarding claim 26, claim 16 is anticipated as described above.
The composition of Liu delivers an optimal range of limiting amino acids: “The results of this study showed substantially greater availability of leucine and methionine with P4 protein than with vegetable proteins (e.g., iAUC of leucine and methionine were ~1.5 and 2 times higher with P4 protein vs. soy). Moreover, P4 protein resulted in a statistically significant increase in arginine availability and a non-significant increase in glycine availability compared to casein and whey (e.g., iAUC arginine and glycine were ~1.4 times higher with P4 protein vs. whey protein). These data indicate that intake of P4 protein can lead to a higher plasma concentration of the limiting amino acid in the protein source compared to the other single protein sources. This finding is relevant, because higher availability of limiting amino acids could increase the efficiency of other amino acids and thus improve protein accretion.” (Liu et al., page 11, para. 2).
Hurt discloses the importance of leucine for muscle synthesis: “Branched-chain amino acids (BCAAs), especially leucine, act as a trigger for increasing muscle protein synthesis. Leucine is an insulin secretagogue and potent activator of the mammalian target of rapamycin (mTOR) nutrient signaling pathway.” (Hurt et al., page 144S, col. 2, para. 8).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to use the composition of Liu to deliver an optimal ratio of limiting amino acids to encourage muscle synthesis as described by Hurt to arrive at the claimed invention.
A person of ordinary skill in the art would be motivated to use this method to treat muscle decline because muscle decline in hospitalized patients is unwanted: “Protein loss, manifested as a reduction in skeletal muscle mass and total body nitrogen content, is observed universally in all critically ill patients. Protein catabolism is part of the metabolic response to critical illness. The magnitude of protein loss is associated with increased morbidity and mortality.1 The depletion of muscle mass seen clinically has been associated with impaired function and poor clinical outcomes.1,2 Adequate protein delivery to hospitalized and critically ill patients is very likely essential for optimal nutrition therapy, but high-quality evidence from clinical trials supporting this view is currently lacking.” (Hurt et al., page 143S, col. 1, para. 2).
A person of ordinary skill in the art would have a reasonable expectation of success because the composition of Liu delivers an optimized amount of leucine accompanied by an optimized amount of other amino acids to complement said leucine: “This finding is relevant, because higher availability of limiting amino acids could increase the efficiency of other amino acids and thus improve protein accretion.” (Liu et al., page 11, para. 2).
Consequently, claim 26 is obvious over Liu et al. as evidenced by Hurt et al. as applied to claim 16 above, further in view of Hurt et al. and rejected.
Regarding claim 27, claim 16 is anticipated as described above. Claim 27 further recites the case wherein the human subject is a human elderly subject who is suffering or at risk of developing sarcopenia or frailty.
Hurt discloses that: “BCAAs (especially leucine) have been shown to stimulate MPS in chronic conditions similar to PICS (eg, advanced age, sarcopenia, and cancer).”
The composition of Liu delivers an optimal range of limiting amino acids: “The results of this study showed substantially greater availability of leucine and methionine with P4 protein than with vegetable proteins (e.g., iAUC of leucine and methionine were ~1.5 and 2 times higher with P4 protein vs. soy). Moreover, P4 protein resulted in a statistically significant increase in arginine availability and a non-significant increase in glycine availability compared to casein and whey (e.g., iAUC arginine and glycine were ~1.4 times higher with P4 protein vs. whey protein). These data indicate that intake of P4 protein can lead to a higher plasma concentration of the limiting amino acid in the protein source compared to the other single protein sources. This finding is relevant, because higher availability of limiting amino acids could increase the efficiency of other amino acids and thus improve protein accretion.” (Liu et al., page 11, para. 2).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to use the composition of Liu to deliver an optimal ratio of limiting amino acids to help prevent sarcopenia as described by Hurt to arrive at the claimed invention.
A person would be motivated to make this combination because sarcopenia is unwanted in the patient population would have a reasonable expectation of success because Liu delivers an optimal amount of leucine and companion amino acids as described above.
Consequently, claim 27 is obvious over Liu et al. as evidenced by Hurt et al. as applied to claim 16 above, further in view of Hurt et al. and rejected.
Regarding claim 28, claim 16 is anticipated as described above. Claim 28 further recites the case wherein the daily amount of protein administered to the human subject is between 1.0 and 1.8 g/kg body weight.
Liu discloses the administration of 18g of protein per subject: “The products were prepared by blending 18g pure protein in 360 mL of water. No extra calories (i.e., fat, carbohydrate, or micronutrients) were added. Sucralose and flavors (i.e., caramel, orange, and peach) were used to improve the taste and palatability of the protein solutions. The protein solutions were sterilized and subsequently homogenized. The five products had a similar pH (around 7.1).” (Liu et al, page 4, para. 2).
MPEP 2144.05(II)(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)”.
Furthermore, Hurt discloses the following: “The International Protein Summit in 2016 brought experts in clinical nutrition and protein metabolism together from around the globe to determine the impact of high-dose protein administration on clinical outcomes and address barriers to its delivery in the critically ill patient. It has been suggested that high doses of protein in the range of 1.2–2.5 g/kg/d may be required in the setting of the intensive care unit (ICU) to optimize nutrition therapy and reduce mortality.”
The range disclosed by Hurt substantially overlaps the claimed range of 1.0-1.8 g/kg/d by claim 28. MPEP 2144.05(I) states: “In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976).”
For these reasons, claim 28 is obvious over Liu et al. as evidenced by Hurt et al. as applied to claim 16 above, further in view of Hurt et al. and rejected.
Regarding claim 32, claim 32 recites a method for prevention and/or treatment of muscle decline, or improving muscle function, in a human subject suffering from metabolic stress and/or starvation following trauma, inflammation, sepsis, critical illness, stroke, cancer or COPD, and wherein the subject is administered with a composition which comprises a protein fraction, the protein fraction provides a balanced amino acid pattern, with numbers in gram per 100 gram of the protein fraction:
PNG
media_image4.png
278
284
media_image4.png
Greyscale
The composition of Liu delivers an optimal range of limiting amino acids: “The results of this study showed substantially greater availability of leucine and methionine with P4 protein than with vegetable proteins (e.g., iAUC of leucine and methionine were ~1.5 and 2 times higher with P4 protein vs. soy). Moreover, P4 protein resulted in a statistically significant increase in arginine availability and a non-significant increase in glycine availability compared to casein and whey (e.g., iAUC arginine and glycine were ~1.4 times higher with P4 protein vs. whey protein). These data indicate that intake of P4 protein can lead to a higher plasma concentration of the limiting amino acid in the protein source compared to the other single protein sources. This finding is relevant, because higher availability of limiting amino acids could increase the efficiency of other amino acids and thus improve protein accretion.” (Liu et al., page 11, para. 2).
Furthermore, Liu et al. discloses the following amino acid pattern for the P4 product:
PNG
media_image2.png
268
241
media_image2.png
Greyscale
PNG
media_image3.png
231
244
media_image3.png
Greyscale
(Liu et al., page 2, Table 1).
These disclosed values read on the ranges in Applicant claim 32.
Hurt discloses the importance of leucine for muscle synthesis: “Branched-chain amino acids (BCAAs), especially leucine, act as a trigger for increasing muscle protein synthesis. Leucine is an insulin secretagogue and potent activator of the mammalian target of rapamycin (mTOR) nutrient signaling pathway.” (Hurt et al., page 144S, col. 2, para. 8).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to use the composition of Liu, having the claimed amino acid ratio, to deliver an optimal ratio of limiting amino acids to encourage muscle synthesis as described by Hurt to arrive at the claimed invention.
A person of ordinary skill in the art would be motivated to use this method to treat muscle decline because muscle decline in hospitalized patients is unwanted: “Protein loss, manifested as a reduction in skeletal muscle mass and total body nitrogen content, is observed universally in all critically ill patients. Protein catabolism is part of the metabolic response to critical illness. The magnitude of protein loss is associated with increased morbidity and mortality.1 The depletion of muscle mass seen clinically has been associated with impaired function and poor clinical outcomes.1,2 Adequate protein delivery to hospitalized and critically ill patients is very likely essential for optimal nutrition therapy, but high-quality evidence from clinical trials supporting this view is currently lacking.” (Hurt et al., page 143S, col. 1, para. 2).
A person of ordinary skill in the art would have a reasonable expectation of success because the composition of Liu delivers an optimized amount of leucine accompanied by an optimized amount of other amino acids to complement said leucine: “This finding is relevant, because higher availability of limiting amino acids could increase the efficiency of other amino acids and thus improve protein accretion.” (Liu et al., page 11, para. 2).
Consequently, claim 32 is obvious over Liu et al. as evidenced by Hurt et al. as applied to claim 16 above, further in view of Hurt et al. and rejected.
Regarding claim 33, claim 32 is obvious as described above. Claim 33 further recites the case wherein the human subject is a human elderly subject of at least 50 years of age. Liu discloses test subjects of 65 years of age or older: ““Eligible subjects were recruited from a healthy volunteer database, who were: (a) aged ≥ 65 years; (b) between 20 and 30 kg/m2 for body mass index; and (c) judged by the investigator to be in good health.” (Liu et al., page 3, para. 1).
Consequently, claim 33 is obvious over Liu et al. as evidenced by Hurt et al. as applied to claim 16 above, further in view of Hurt et al. and rejected.
Conclusion
No claimed is allowed.
Claims 16-33 are rejected.
Claim 1 is objected to.
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/DAVID PAUL BOWLES/ Examiner, Art Unit 1654
/LIANKO G GARYU/ Supervisory Patent Examiner, Art Unit 1654