EP-4734770-A1 - COMPOUNDS THAT MODULATE GPRC6A RECEPTOR AND PET FOOD PRODUCTS CONTAINING THE SAME

Abstract

The presently disclosed subject matter relates to compounds and/or flavor compositions for enhancing palatability of pet food products. The presently disclosed subject matter also relates to compounds that modulate the activity of a GPRC6A taste receptor.

Inventors

• MCGRANE, Scott Joseph
• GIBBS, Matthew Ronald
• KLEBANSKY, BORIS

Assignees

• Mars, Incorporated

Dates

Publication Date

20260506

Application Date

20240624

Claims (1)

1. 069269.0689 PATENT WHAT IS CLAIMED IS: 1. A pet food product comprising: a) one or more compounds that bind to a GPRC6A receptor or a functional fragment thereof; or b) a flavor composition comprising one or more compounds that bind to a GPRC6A receptor or a functional fragment thereof. 2. The pet food product of claim 1, wherein the pet food product has enhanced palatability. 3. The pet food product of claim 1 or 2, wherein the one or more compound increases, decreases or modulates the biological activity of the GPRC6A receptor. 4. The pet food product of any one of claims 1-3, wherein the one or more compound is selected from the group consisting of amino acids, peptides, hormones, ions, metals, butanoic acid-based compounds, propanoic acid-based compounds, pentanoic acid-based compounds, carboxylic acid-based compounds, derivatives thereof, and combinations thereof. 5. The pet food product of any one of claims 1-4, wherein the one or more compound has an EC50 value of no more than about 50 mM in connection with a biological activity of the GPRC6A receptor. 6. The pet food product of any one of claims 1-5, wherein the compound has the formula: . 7. The pet food product of claim 6, wherein R1 is selected from the group consisting of H, C 1 -C 20 alkyl, branched C 1 -C 20 alkyl, unbranched C 1 -C 20 alkyl, C 1 -C 20 alkenyl, brached C 1 - C 20 alkenyl, unbranched C 1 -C 20 alkenyl, C 1 -C 20 alkynyl, branched C 1 -C 20 alkynyl, unbranched C1-C20 alkynyl, arylalkyl, aryl, cycloalkyl, heterocyclyl, heteroaryl, heteroarylalkyl, haloalkyl, CF3, halogen, phenyl, -C(O)R3, -COOR3, -NR3R4, -NO2, -OH, -OR 3 , -CONR 3 R 4 , -S-Aryl, -O-Aryl, -N-Aryl, -NO 2 , -SO 3 H, -SO 2 R 3 , -NHOH, -C=CR 3 , - C=NOH, -OP(O)(OH)2, and CHO. 8. The pet food product of claim 7, wherein R3 and R4 are each independently selected from the group consisting of H, C 1 -C 20 alkyl, branched C 1 -C 20 alkyl, unbranched C 1 -C 20 alkyl, C 1 -C 20 alkenyl, brached C 1 -C 20 alkenyl, unbranched C 1 -C 20 alkenyl, C 1 -C 20 alkynyl, branched C1-C20 alkynyl, unbranched C1-C20 alkynyl, arylalkyl, aryl, cycloalkyl, heterocyclyl, heteroaryl, heteroarylalkyl, haloalkyl, CF 3 , and halogen. 9. The pet food product of any one of claims 6-8, wherein R 1 is substituted. Active 118427983.2 51 069269.0689 PATENT 10. The pet food product of any one of claims 6-9, wherein R2 is selected from the group consisting of H, C 1 -C 20 alkyl, branched C 1 -C 20 alkyl, unbranched C 1 -C 20 alkyl, C 1 -C 20 alkenyl, brached C 1 -C 20 alkenyl, unbranched C 1 -C 20 alkenyl, C 1 -C 20 alkynyl, branched C 1 - C20 alkynyl, unbranched C1-C20 alkynyl, arylalkyl, aryl, cycloalkyl, heterocyclyl, heteroaryl, and heteroarylalkyl. 11. The pet food product of any one of claims 6-10, wherein R 2 is H or methyl. 12. The pet food product of any one of claims 1-5, wherein the compound has the formula: . 13. The pet food of claim 12, wherein R is selected from the group consisting of H, C 1 -C 20 alkyl, branched C1-C20 alkyl, unbranched C1-C20 alkyl, C1-C20 alkenyl, brached C1-C20 alkenyl, unbranched C 1 -C 20 alkenyl, C 1 -C 20 alkynyl, branched C 1 -C 20 alkynyl, unbranched C 1 -C 20 alkynyl, arylalkyl, aryl, cycloalkyl, heterocyclyl, heteroaryl, heteroarylalkyl, haloalkyl, CF3, halogen, phenyl, -C(O)R3, -COOR3, -NR3R4, -NO2, -OH, -OR3, - CONR3R4, -S-Aryl, -O-Aryl, -N-Aryl, -NO2, -SO3H, -SO2R3, -NHOH, -C=CR3, -C=NOH, -OP(O)(OH) 2 , and CHO. 14. The pet food product of claim 13, wherein R 1 and R 2 are each independently selected from the group consisting of H, C1-C20 alkyl, branched C1-C20 alkyl, unbranched C1-C20 alkyl, C 1 -C 20 alkenyl, brached C 1 -C 20 alkenyl, unbranched C 1 -C 20 alkenyl, C 1 -C 20 alkynyl, branched C 1 -C 20 alkynyl, unbranched C 1 -C 20 alkynyl, arylalkyl, aryl, cycloalkyl, heterocyclyl, heteroaryl, heteroarylalkyl, haloalkyl, CF3, and halogen. 15. The pet food product of any one of claims 12-14, wherein R is substituted. 16. The pet food product of any one of claims 6-15, wherein the compound comprises: a) includes an L-amino-acid; b) includes one carbon after the ^^-carbon of the amino-acid unit; c) can include a positively-charged group at a distance up to ~9A from the ^^-carbon (alpha carbon denoting the carbon of the compound to the amino group to the carboxyl group); and/or d) does not include a negatively-charged group at a distance up to ~9A from ^^-carbon. 17. The pet food product of any one of claims 1-16, wherein the one or more compound is present at a concentration of between about 0.0001% and about 2% weight/weight (w/w) in the pet food product. Active 118427983.2 52 069269.0689 PATENT 18. The pet food product of any one of claims 1-16, wherein the flavor composition is present at a concentration of between about 0.0001% and about 2% weight/weight (w/w) in the pet food product. 19. The pet food product of any one of claims 1-16, wherein the one or more compound is present at a concentration of between about 0.00001% and about 5% in the flavor composition. 20. The pet food product of any one of claims 1-19, wherein the GPRC6A receptor is a feline GPRC6A receptor. 21. The pet food product of any one of claims 1-19, wherein the GPRC6A receptor is a canine GPRC6A receptor. 22. A method for increasing palatability of a pet food product, the method comprising providing a pet food product; and a) admixing the pet food product with at least one compound that binds to one or more amino acids of a GPRC6A receptor; or b) admixing the pet food product with at least one flavor composition, wherein the flavor composition comprises a compound that binds to one or more amino acids of a GPRC6A receptor. 23. The method of claim 22, wherein the at least one compound is selected from the group consisting of amino acids, peptides, hormones, ions, metals, butanoic acid-based compounds, propanoic acid-based compounds, pentanoic acid-based compounds, carboxylic acid-based compounds, derivates thereof, and combinations thereof. 24. The method of claim 22 or 23, wherein the compound has the formula: . 25. The method of claim 24, wherein R 1 is selected from the group consisting of H, C 1 -C 20 alkyl, branched C 1 -C 20 alkyl, unbranched C 1 -C 20 alkyl, C 1 -C 20 alkenyl, brached C 1 -C 20 alkenyl, unbranched C1-C20 alkenyl, C1-C20 alkynyl, branched C1-C20 alkynyl, unbranched C1-C20 alkynyl, arylalkyl, aryl, cycloalkyl, heterocyclyl, heteroaryl, heteroarylalkyl, haloalkyl, CF 3 , halogen, phenyl, -C(O)R 3 , -COOR 3 , -NR 3 R 4 , -NO 2 , -OH, -OR 3 , - CONR3R4, -S-Aryl, -O-Aryl, -N-Aryl, -NO2, -SO3H, -SO2R3, -NHOH, -C=CR3, -C=NOH, -OP(O)(OH)2, and CHO. 26. The method of claim 25, wherein R 3 and R 4 are each independently selected from the group consisting of H, C1-C20 alkyl, branched C1-C20 alkyl, unbranched C1-C20 alkyl, C1-C20 Active 118427983.2 53 069269.0689 PATENT alkenyl, brached C1-C20 alkenyl, unbranched C1-C20 alkenyl, C1-C20 alkynyl, branched C1- C 20 alkynyl, unbranched C 1 -C 20 alkynyl, arylalkyl, aryl, cycloalkyl, heterocyclyl, heteroaryl, heteroarylalkyl, haloalkyl, CF 3 , and halogen. 27. The method of any one of claims 24-26, wherein R1 is substituted. 28. The method of any one of claims 24-27, wherein R2 is selected from the group consisting of H, C 1 -C 20 alkyl, branched C 1 -C 20 alkyl, unbranched C 1 -C 20 alkyl, C 1 -C 20 alkenyl, brached C1-C20 alkenyl, unbranched C1-C20 alkenyl, C1-C20 alkynyl, branched C1-C20 alkynyl, unbranched C1-C20 alkynyl, arylalkyl, aryl, cycloalkyl, heterocyclyl, heteroaryl, and heteroarylalkyl. 29. The method of any one of claims 24-28, wherein R2 is H or methyl. 30. The method of claim 22 or 23, wherein the compound has the formula: . 31. The method of claim 30, wherein R is selected from the group consisting of H, C1-C20 alkyl, branched C1-C20 alkyl, unbranched C1-C20 alkyl, C1-C20 alkenyl, brached C1-C20 alkenyl, unbranched C 1 -C 20 alkenyl, C 1 -C 20 alkynyl, branched C 1 -C 20 alkynyl, unbranched C 1 -C 20 alkynyl, arylalkyl, aryl, cycloalkyl, heterocyclyl, heteroaryl, heteroarylalkyl, haloalkyl, CF3, halogen, phenyl, -C(O)R3, -COOR3, -NR3R4, -NO2, -OH, -OR3, - CONR 3 R 4 , -S-Aryl, -O-Aryl, -N-Aryl, -NO 2 , -SO 3 H, -SO 2 R 3 , -NHOH, -C=CR 3 , -C=NOH, -OP(O)(OH) 2 , and CHO. 32. The method of claim 31, wherein R1 and R2 are each independently selected from the group consisting of H, C 1 -C 20 alkyl, branched C 1 -C 20 alkyl, unbranched C 1 -C 20 alkyl, C 1 -C 20 alkenyl, brached C 1 -C 20 alkenyl, unbranched C 1 -C 20 alkenyl, C 1 -C 20 alkynyl, branched C 1 - C20 alkynyl, unbranched C1-C20 alkynyl, arylalkyl, aryl, cycloalkyl, heterocyclyl, heteroaryl, heteroarylalkyl, haloalkyl, CF3, and halogen. 33. The method of any one of claims 30-32, wherein R is substituted. 34. The method of any one of claims 24-33, wherein the compound comprises: a) includes an L-amino-acid; b) includes one carbon after the ^^-carbon of the amino-acid unit; c) can include a positively-charged group at a distance up to ~9A from the ^^-carbon (alpha carbon denoting the carbon of the compound to the amino group to the carboxyl group); and/or d) does not include a negatively-charged group at a distance up to ~9A from ^^-carbon. Active 118427983.2 54 069269.0689 PATENT 35. The method of any one of claims 22-34, wherein the at least one compound binds to one or more amino acids of a Venus Flytrap Domain of the GPRC6A receptor. 36. The method of any one of claims 22-35, wherein the least one compound binds to one or more amino acids of a 7-transmembrane domain of the GPRC6A receptor. 37. The method of any one of claims 22-36, wherein the GPRC6A receptor is a feline GPRC6A. 38. The method of claim 37, wherein the at least one compound binds to one or more amino acids of the feline GPRC6A receptor selected from the group consisting of Tyr148, Ser149, Glu170, Thr172, Asp 218, Tyr220, Arg279, Asp303, Asn304, Thr307, Arg399, Asn400, and combination thereof. 39. The method of claim 37 or 38, wherein the compound binds to one or more amino acids of the feline GPRC6A receptor selected from the group consisting of Arg662, Gln663, Phe666, Gly667, Phe670, Gln715, Glu746, Ala751, Phe752, Met755, Leu756, Ile759, Tyr793, Trp797, Phe800, Tyr804, Glu816, Val819, Ile820, and combinations thereof. 40. The method of any one of claims 22-36, wherein the GPRC6A receptor is a canine GPRC6A. 41. The method of claim 40, wherein the at least one compound binds to one or more amino acids of the canine GPRC6A receptor selected from the group consisting of Tyr148, Ser149, Glu170, Thr172, Asp 218, Tyr220, Arg279, Asp303, Asn304, Met307, Arg399, Asn400, and combination thereof. 42. The method of claim 40 or 41, wherein the compound binds to one or more amino acids of the GPRC6A receptor selected from the group consisting of Arg662, Gln663, Phe666, Gly667, Phe670, Gln715, Glu746, Ala751, Phe752, Met755, Leu756, Ile759, Tyr793, Trp797, Phe800, Tyr804, Glu816, Val819, Ile820, and combinations thereof. 43. The method of any one of claims 22-42, wherein the at least one compound is present at a concentration of between about 0.0001% and about 2% in the pet food product. 44. The method of any one of claims 22-42, wherein the flavor composition is present at a concentration of between about 0.001% and about 2% in the pet food product. 45. The method of any one of claims 22-42, wherein the at least one compound is present at a concentration of between about 0.00001% and about 5% in the flavor composition. 46. The method of any one of claims 22-45, wherein the method comprises thermal processing of a food product precursor, wherein the compound is generated during the thermal processing. Active 118427983.2 55

Description

069269.0689 PATENT COMPOUNDS THAT MODULATE GPRC6A RECEPTOR AND PET FOOD PRODUCTS CONTAINING THE SAME CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to U.S. Provisional Application No.63/510,968, filed on June 29, 2023, the contents of which are incorporated by reference herein in their entirety and to which priority is claimed. SEQUENCE LISTING The instant application contains a Sequence Listing which has been submitted herewith and is hereby incorporated by reference in its entirety. Said .xml copy, created on June 05, 2024 is named 0692690689.xml, and is 17,754 bytes in size. FIELD The presently disclosed subject matter relates to flavor compositions and/or compounds that interact with a GPRC6A receptor for modulating taste. The flavor compositions and/or compounds can be used to enhance or modify the palatability, taste and/or flavor of pet food products. The flavor compositions can include one or more combinations of compounds and can either be added to pet food products in various delivery system formats or be generated during a manufacturing process of a pet food product. BACKGROUND Taste profiles for edible compositions include basic tastes such as sweet, salt, bitter, sour, umami and kokumi. Taste profiles have also been described as including free fatty acid tastes. Chemical compounds that elicit these tastes are often referred to as tastants. Without being bound by theory, it is hypothesized that tastants are sensed by taste receptors in the mouth and throat which transmit signals to the brain where the tastants and resulting taste profiles are registered. Pet food manufacturers have a long-standing desire to provide pet food products that have high nutritional value. In addition, and with particular regard to cat and dog foods, pet food manufacturers desire a high degree of palatability so that pets can receive the full nutritional benefit from their food. Domestic animals are notoriously finicky in their food preferences and often refuse to eat a pet food product that it has accepted over time or refuse to eat any more than a minimal amount of a pet food product. This phenomenon can be, in part, due to the subtle differences in the sensory profiles of the raw material, which can be perceived by the domestic animals because of their gustatory and olfactory systems. As a result, pet owners frequently Active 118427983.2 1 069269.0689 PATENT change types and brands of pet food in order to maintain their pets in a healthy and contented condition. While there have been recent advances in taste and flavor technologies, there remains a need for compounds that can enhance or modify the palatability of pet food products by enhancing or modifying the taste, texture and/or flavor profiles of the pet food product. The enhancement or modification can be to increase the intensity of a desirable attribute, to replace a desirable attribute not present or somehow lost in the pet food product, or to decrease the intensity of an undesirable attribute. In particular, it is desirable to increase the intensity of a desirable tastant in a pet food product. Therefore, there remains a need in the art for compositions to enhance the palatability and/or modulate the kokumi taste of pet food products. SUMMARY OF THE INVENTION In certain embodiments, the present disclosure relates to a pet food product including: (a) one or more compounds that bind to a GPRC6A receptor or a functional fragment thereof; or (b) a flavor composition including one or more compounds that bind to a GPRC6A receptor or a functional fragment thereof. In certain embodiments, the pet food product has enhanced palatability. In certain embodiments, the one or more compound increases, decreases or modulates the biological activity of the GPRC6A receptor. In certain embodiments, the one or more compound is selected from the group consisting of amino acids, peptides, hormones, ions, metals, butanoic acid-based compounds, propanoic acid-based compounds, pentanoic acid-based compounds, carboxylic acid- based compounds, derivatives thereof, and combinations thereof. In certain embodiments, the one or more compound has an EC50 value of no more than about 50 mM in connection with a biological activity of the GPRC6A receptor. In certain embodiments, the compound has the formula: . In certain embodiments, R1 is selected from the group selected from the group consisting of H, C1-C20 alkyl, branched C1-C20 alkyl, unbranched C1-C20 alkyl, C1-C20 alkenyl, brached C1- C20 alkenyl, unbranched C1-C20 alkenyl, C1-C20 alkynyl, branched C1-C20 alkynyl, unbranched C1- C20 alkynyl, arylalkyl, aryl, cycloalkyl, heterocyclyl, heteroaryl, heteroarylalkyl, haloalkyl, CF3, halogen, phenyl, -C(O)R3, -COOR3, -NR3R4, -NO2, -OH, -OR3, -CONR3R4, -S-Aryl, -O-Aryl, - N-Aryl, -NO2, -SO3H, -SO2R3, -NHOH, -C=CR3, -C=NOH, -OP(O)(OH)2, and CHO. In certain Active 118427983.2 2 069269.0689 PATENT embodiments, R3 and R4 are each independently selected from the