Use of a polypeptide for the prevention or treatment of allergic conjunctivitis

Abstract

The present disclosure provides a polypeptide for preventing or treating allergic conjunctivitis. Also provided is a method for treating or preventing allergic conjunctivitis in a subject in need thereof, comprising administering to the subject an effective amount of any of the polypeptides.

Description

(19) State Intellectual Property Office (12) Invention Patent Application (10) Application Publication Number (43) Application Publication Date (21) Application Number 202480030908.9 (22) Application Date 2024.03.13 (66) Domestic Priority Data PCT / CN2023 / 081353 2023.03.14 CN (85) PCT International Application Entering National Phase Date 2025.11.06 (86) PCT International Application Application Data PCT / CN2024 / 081353 2024.03.13 (87) PCT International Application Publication Data WO2024 / 188256 EN 2024.09.19 (71) Applicant Shanghai Puyou Biomedical Co., Ltd. Address 6, Lane 99, Shenmei Road, Pudong New Area, Shanghai 201321, China Building A (72) Inventors: Zhang Yinghao, Yan Guirui (74) Patent Agency: Beijing Anxin Fangda Intellectual Property Agency Co., Ltd. 11262 Patent Attorneys: Xu Aiwen, Wu Jingjing (51) Int.Cl. C07K 14 / 47 (2006.01) C07K 19 / 00 (2006.01) A61K 38 / 17 (2006.01) A61P 27 / 02 (2006.01) (54) Invention Title: Use of a polypeptide for the prevention or treatment of allergic conjunctivitis (57) Abstract: This disclosure provides a polypeptide for the prevention or treatment of allergic conjunctivitis. A method for treating or preventing allergic conjunctivitis in a subject in need is also provided, comprising administering an effective amount of any of the polypeptides to the subject. Claims 20 pages, Description 68 pages, Drawings 1 page, CN 121079312 A 2025.12.05 CN 1 21 07 93 12 A 1. A method for treating or preventing allergic conjunctivitis in a subject in need, comprising administering to the subject an effective amount of an artificial polypeptide of formula (I): X-Y (I), wherein X is a portion comprising a sequence having at least 80% identity with SEQ ID NO: 1, and Y is a portion comprising 10 to 50 amino acids, at least 50% of which are selected from I, V, L, F, C, M, and A; wherein the total number of cysteine ​​(C) contained in Y is less than 5. 2. The method according to claim 1, wherein X comprises a sequence having at least 90% identity with SEQ ID NO: 1, X comprises a sequence having at least 95% identity with SEQ ID NO: 1, or X comprises the sequence of SEQ ID NO: 1. 3. The method according to claim 1 or 2, wherein at least 50% of the amino acids in X are selected from R, K, N, D, Q, E and H.4. The method according to any one of claims 1 to 3, wherein the total number of cysteine ​​(C) contained in Y is less than 4, the total number of cysteine ​​(C) contained in Y is less than 3, or the total number of cysteine ​​(C) contained in Y is less than 2. 5. The method according to any one of claims 1 to 4, wherein the total number of hydrophobic amino acids in Y is greater than 8, the total number of hydrophobic amino acids in Y is greater than 12, the total number of hydrophobic amino acids in Y is greater than 15, and / or the total number of hydrophilic amino acids in Y does not exceed 5. 6. The method according to any one of claims 1 to 5, wherein X contains a sequence having at least 90% identity with any one of SEQ ID NO: 81-83. 7. The method according to any one of claims 1 to 6, wherein Y contains a sequence having at least 90% identity with any one of SEQ ID NO: 3-15, 58-61, and 84-85, or Y contains a sequence having at least 90% identity with any one of SEQ ID NO: 3-18, 58-61, and 84-85. 8. The method of any one of claims 1 to 7, wherein the polypeptide comprises a sequence having at least 90% identity with any one of SEQ ID NO: 29-41, 54-57, 75, and 91-95. 9. The method of any one of claims 1 to 8, wherein the allergic conjunctivitis is at least one selected from seasonal allergic conjunctivitis, perennial allergic conjunctivitis, vernal keratoconjunctivitis, giant papillary conjunctivitis, atopic keratoconjunctivitis, and herpetic keratoconjunctivitis. 10. The method of claim 9, wherein the seasonal allergic conjunctivitis is caused by or partially by a seasonal allergen. 11. The method of claim 10, wherein the seasonal allergen is at least one selected from tree pollen, weed pollen, grass pollen, and mold spores. 12. The method of claim 9, wherein the perennial allergic conjunctivitis is caused by or partially by a perennial allergen. 13. The method of claim 12, wherein the perennial allergen is at least one selected from dust mites, cockroaches, and animal dander. 14. The method of claim 9, wherein the vernal keratoconjunctivitis is at least one selected from eyelid vernal keratoconjunctivitis, limbal vernal keratoconjunctivitis, and mixed vernal keratoconjunctivitis. 15. The method of claim 9, wherein the giant papillary conjunctivitis is caused, or is partially caused, by repetitive mechanical irritation of the conjunctiva. 16. The method of claim 15, wherein the repetitive mechanical irritation of the conjunctiva is associated with at least one selected from contact lens wear, use of ocular prostheses, use of conjunctival sutures, use of prominent scleral buckles, and corneal scarring.Claims 1 / 20 page 2 CN 121079312 A 17. The method of claim 9, wherein the atopic keratoconjunctivitis is accompanied by atopic dermatitis and / or asthma. 18. The method of claim 9, wherein the herpetic keratoconjunctivitis is caused by or in part by a delayed hypersensitivity reaction or inflammatory reaction of the cornea and conjunctiva to antigens expressed by various pathogens. 19. The method of claim 18, wherein the pathogen is at least one selected from bacteria (e.g., Staphylococcus aureus, Streptococcus viridans, Mycobacterium tuberculosis), viruses (e.g., herpes simplex virus), chlamydia, fungi (e.g., Candida albicans), and parasites (e.g., tapeworms such as Hymenolepis microsporum; and nematodes). 20. The method of any one of claims 1 to 19, wherein the subject does not suffer from any ocular disease selected from viral conjunctivitis, bacterial conjunctivitis, chemical conjunctivitis, and dry eye syndrome or dry eye-related conditions. 21. The method according to any one of claims 1 to 20, wherein the subject experiences at least one symptom prior to administration of the artificial polypeptide of formula (I), the symptom being selected from conjunctival redness, conjunctival edema, conjunctival hyperemia, eyelid redness, eyelid edema, eyelid hyperemia, itchy eyes, visible corneal damage, mucus secretion, watery secretion, tearing, photophobia, foreign body sensation, and difficulty opening the eyes. 22. The method according to any one of claims 1 to 21, wherein the subject, after administration of at least one dose of the artificial polypeptide of formula (I), shows a reduction in at least one symptom selected from conjunctival redness, conjunctival edema, conjunctival hyperemia, eyelid redness, eyelid edema, eyelid hyperemia, itchy eyes, visible corneal damage, mucus secretion, watery secretion, tearing, photophobia, foreign body sensation, and difficulty opening the eyes. 23. The method according to any one of claims 1 to 22, wherein the subject, after administration of at least one dose of the artificial polypeptide of formula (I), shows improvement in at least one tissue selected from the conjunctiva, cornea, anterior chamber, iris, pupil, vitreous body, and fundus. 24. A method for treating or preventing allergic conjunctivitis in a subject in need, comprising administering to the subject an effective amount of an artificial polypeptide of formula (II): X-Y(II), wherein X is a portion comprising a sequence having at least 80% identity with SEQ ID NO: 1, and Y is a portion comprising 10 to 50 amino acids, at least 50% of said amino acids being selected from I, V, L, F, C, M, and A; wherein Y comprises a sequence having at most 90% identity with SEQ ID NO: 2. 25. The method of claim 24, wherein X comprises a sequence having at least 90% identity with SEQ ID NO: 1, X comprises a sequence having at least 95% identity with SEQ ID NO: 1, or X comprises the sequence of SEQ ID NO: 1.26. The method according to claim 24 or 25, wherein at least 50% of the amino acids in X are selected from R, K, N, D, Q, E, and H. 27. The method according to any one of claims 24 to 26, wherein Y comprises a sequence having at most 80% identity with SEQ ID NO: 2, Y comprises a sequence having at most 70% identity with SEQ ID NO: 2, or Y comprises a sequence having at most 50% identity with SEQ ID NO: 2. 28. The method according to any one of claims 24 to 27, wherein the total number of hydrophobic amino acids in Y is greater than 8, the total number of hydrophobic amino acids in Y is greater than 12, the total number of hydrophobic amino acids in Y is greater than 15, and / or the total number of hydrophilic amino acids in Y does not exceed 5. 29. The method according to any one of claims 24 to 28, wherein Y comprises a sequence having at least 90% identity with any one of SEQ ID NO: 16-18, or Y comprises a sequence having at least 95% identity with any one of SEQ ID NO: 16-18. 30. The method of any one of claims 24 to 29, wherein the polypeptide comprises a sequence having at least 90% identity with any one of SEQ ID NO: 42-44. Claims 2 / 20 Page 3 CN 121079312 A 31. The method of any one of claims 24 to 30, wherein the allergic conjunctivitis is at least one selected from seasonal allergic conjunctivitis, perennial allergic conjunctivitis, vernal keratoconjunctivitis, giant papillary conjunctivitis, atopic keratoconjunctivitis, and herpetic keratoconjunctivitis. 32. The method of claim 31, wherein the seasonal allergic conjunctivitis is caused by or partially by a seasonal allergen. 33. The method of claim 32, wherein the seasonal allergen is at least one selected from tree pollen, weed pollen, grass pollen, and mold spores. 34. The method of claim 31, wherein the perennial allergic conjunctivitis is caused by or partially by a perennial allergen. 35. The method of claim 34, wherein the perennial allergen is at least one selected from dust mites, cockroaches, and animal dander. 36. The method of claim 31, wherein the vernal keratoconjunctivitis is at least one selected from eyelid vernal keratoconjunctivitis, limbal vernal keratoconjunctivitis, and mixed vernal keratoconjunctivitis. 37. The method of claim 31, wherein the giant papillary conjunctivitis is caused, or is partially caused, by repetitive mechanical irritation of the conjunctiva. 38. The method of claim 37, wherein the repetitive mechanical irritation of the conjunctiva is associated with at least one selected from contact lens wear, use of ocular prostheses, use of conjunctival sutures, use of prominent scleral buckles, and corneal scarring.39. The method of claim 31, wherein the atopic keratoconjunctivitis is accompanied by atopic dermatitis and / or asthma. 40. The method of claim 31, wherein the herpetic keratoconjunctivitis is caused, or is partially caused, by a delayed-type hypersensitivity or inflammatory response of the cornea and conjunctiva to antigens expressed by various pathogens. 41. The method of claim 40, wherein the pathogen is at least one selected from bacteria (e.g., Staphylococcus aureus, Streptococcus viridans, Mycobacterium tuberculosis), viruses (e.g., herpes simplex virus), chlamydia, fungi (e.g., Candida albicans), and parasites (e.g., tapeworms such as Hymenolepis microsporum; and nematodes). 42. The method of any one of claims 24 to 41, wherein the subject does not suffer from any ocular disease selected from viral conjunctivitis, bacterial conjunctivitis, chemical conjunctivitis, and dry eye syndrome or dry eye-related conditions. 43. The method according to any one of claims 24 to 42, wherein the subject experiences at least one symptom prior to administration of the artificial polypeptide of formula (II), the symptom being selected from conjunctival redness, conjunctival edema, conjunctival hyperemia, eyelid redness, eyelid edema, eyelid hyperemia, itchy eyes, visible corneal damage, mucus secretion, watery secretion, tearing, photophobia, foreign body sensation, and difficulty opening the eyes. 44. The method according to any one of claims 24 to 43, wherein the subject, after administration of at least one dose of the artificial polypeptide of formula (II), shows a reduction in at least one symptom selected from conjunctival redness, conjunctival edema, conjunctival hyperemia, eyelid redness, eyelid edema, eyelid hyperemia, itchy eyes, visible corneal damage, mucus secretion, watery secretion, tearing, photophobia, foreign body sensation, and difficulty opening the eyes. 45. The method according to any one of claims 24 to 44, wherein the subject shows improvement in at least one tissue selected from the conjunctiva, cornea, anterior chamber, iris, pupil, vitreous body, and fundus after administration of at least one dose of the artificial polypeptide of formula (II). 46. A method for treating or preventing allergic conjunctivitis in a subject in need, comprising administering an effective amount of the artificial polypeptide of formula (III) to the subject: AX-Y(III), wherein X is a portion comprising 40 to 65 amino acids, at least 50% of which are selected from H, R, K, D, Q, N, and E; and Y is a portion comprising a sequence having at least 80% identity with SEQ ID NO: 2, wherein the total number of H, R, K, D, Q, N, and E in X is less than 33. 47. The method of claim 46, wherein Y comprises a sequence having at least 90% identity with SEQ ID NO: 2, Y comprises a sequence having at least 95% identity with SEQ ID NO: 2, or Y comprises a sequence of SEQ ID NO: 2.48. The method according to claim 46 or 47, wherein at least 50% of the amino acids in Y are selected from I, V, L, F, C, M, and A. 49. The method according to any one of claims 46 to 48, wherein the total number of H, R, K, D, Q, N, and E in X is less than 30, the total number of H, R, K, D, Q, N, and E in X is less than 25, or the total number of H, R, K, D, Q, N, and E in X is less than 20. 50. The method according to any one of claims 46 to 49, wherein the total number of hydrophilic amino acids in X is greater than 10, the total number of hydrophilic amino acids in X is greater than 15, the total number of hydrophilic amino acids in X is greater than 20, the total number of hydrophilic amino acids in X is greater than 25, the total number of hydrophobic amino acids in X is not more than 15, and / or the total number of hydrophobic amino acids in X is not more than 10. 51. The method of any one of claims 46 to 50, wherein X comprises a sequence having at least 90% identity with any one of SEQ ID NO: 23-27, or X comprises a sequence having at least 95% identity with any one of SEQ ID NO: 23-27. 52. The method of any one of claims 46 to 51, wherein the polypeptide comprises a sequence having at least 90% identity with any one of SEQ ID NO: 49-53. 53. The method of any one of claims 46 to 52, wherein the allergic conjunctivitis is at least one selected from seasonal allergic conjunctivitis, perennial allergic conjunctivitis, vernal keratoconjunctivitis, giant papillary conjunctivitis, atopic keratoconjunctivitis, and herpetic keratoconjunctivitis. 54. The method of claim 53, wherein the seasonal allergic conjunctivitis is caused by or partially by a seasonal allergen. 55. The method of claim 54, wherein the seasonal allergen is at least one selected from tree pollen, weed pollen, grass pollen, and mold spores. 56. The method of claim 53, wherein the perennial allergic conjunctivitis is caused by or partially by a perennial allergen. 57. The method of claim 56, wherein the perennial allergen is at least one selected from dust mites, cockroaches, and animal dander. 58. The method of claim 53, wherein the vernal keratoconjunctivitis is at least one selected from eyelid vernal keratoconjunctivitis, limbal vernal keratoconjunctivitis, and mixed vernal keratoconjunctivitis. 59. The method of claim 53, wherein the giant papillary conjunctivitis is caused by or partially by repetitive mechanical irritation of the conjunctiva. 60. The method of claim 59, wherein the repetitive mechanical irritation of the conjunctiva is associated with at least one selected from contact lens wear, use of ocular prostheses, use of conjunctival sutures, use of prominent scleral buckles, and corneal scarring.61. The method of claim 53, wherein the atopic keratoconjunctivitis is accompanied by atopic dermatitis and / or asthma. 62. The method of claim 53, wherein the herpetic keratoconjunctivitis is caused, or is partially caused, by a delayed-type hypersensitivity or inflammatory reaction of the cornea and conjunctiva to antigens expressed by various pathogens. 63. The method of claim 62, wherein the pathogen is at least one selected from bacteria (e.g., Staphylococcus aureus, Streptococcus viridans, Mycobacterium tuberculosis), viruses (e.g., herpes simplex virus), chlamydia, fungi (e.g., Candida albicans), and parasites (e.g., tapeworms such as Hymenolepis microsporum; and nematodes). 64. The method of any one of claims 46 to 63, wherein the subject does not suffer from any ocular disease selected from viral conjunctivitis, bacterial conjunctivitis, chemical conjunctivitis, and dry eye syndrome or dry eye-related conditions. 65. The method according to any one of claims 46 to 64, wherein the subject experiences at least one symptom prior to administration of the artificial polypeptide of formula (III), the symptom being selected from conjunctival redness, conjunctival edema, conjunctival hyperemia, eyelid redness, eyelid edema, eyelid hyperemia, itchy eyes, visible corneal damage, mucus secretion, watery secretion, tearing, photophobia, foreign body sensation, and difficulty opening the eyes. 66. The method according to any one of claims 46 to 65, wherein the subject, after administration of at least one dose of the artificial polypeptide of formula (III), shows a reduction in at least one symptom selected from conjunctival redness, conjunctival edema, conjunctival hyperemia, eyelid redness, eyelid edema, eyelid hyperemia, itchy eyes, visible corneal damage, mucus secretion, watery secretion, tearing, photophobia, foreign body sensation, and difficulty opening the eyes. 67. The method according to any one of claims 46 to 66, wherein the subject shows improvement in at least one tissue selected from the conjunctiva, cornea, anterior chamber, iris, pupil, vitreous body, and fundus after administration of at least one dose of the artificial polypeptide of formula (III). 68. A method for treating or preventing allergic conjunctivitis in a subject in need, comprising administering to the subject an effective amount of the artificial polypeptide of formula (IV): X-Y (IV), wherein X is a portion comprising 40 to 65 amino acids, at least 50% of which are selected from H, R, K, D, Q, N, and E; and Y is a portion comprising a sequence having at least 80% identity with SEQ ID NO: 2, wherein X comprises a sequence having at most 90% identity with SEQ ID NO: 1.69. The method of claim 68, wherein X comprises a sequence having at most 80% identity with SEQ ID NO: 1, X comprises a sequence having at most 70% identity with SEQ ID NO: 1, or X comprises a sequence having at most 50% identity with SEQ ID NO: 1. 70. The method of claim 68 or 69, wherein Y comprises a sequence having at least 90% identity with SEQ ID NO: 2, Y comprises a sequence having at least 95% identity with SEQ ID NO: 2, or Y comprises the sequence of SEQ ID NO: 2. 71. The method of any one of claims 68 to 70, wherein at least 50% of the amino acids in Y are selected from I, V, L, F, C, M, and A. 72. The method according to any one of claims 68 to 71, wherein the total number of hydrophilic amino acids in X is greater than 10, the total number of hydrophilic amino acids in X is greater than 15, the total number of hydrophilic amino acids in X is greater than 20, the total number of hydrophilic amino acids in X is greater than 25, the total number of hydrophobic amino acids in X is not more than 15, and / or the total number of hydrophobic amino acids in X is not more than 10. 73. The method according to any one of claims 68 to 72, wherein X comprises a sequence having at least 90% identity with any one of SEQ ID NO: 19-22 and 76-79, or X comprises a sequence having at least 95% identity with any one of SEQ ID NO: 19-22 and 76-79. 74. The method according to any one of claims 68 to 73, wherein the polypeptide comprises a sequence having at least 90% identity with any one of SEQ ID NO: 45-48 and 86-89. Claims 5 / 20, page 6, CN 121079312 A 75. The method according to any one of claims 68 to 74, wherein the allergic conjunctivitis is at least one selected from seasonal allergic conjunctivitis, perennial allergic conjunctivitis, vernal keratoconjunctivitis, giant papillary conjunctivitis, atopic keratoconjunctivitis, and herpetic keratoconjunctivitis. 76. The method according to claim 75, wherein the seasonal allergic conjunctivitis is caused by or partially by a seasonal allergen. 77. The method according to claim 76, wherein the seasonal allergen is at least one selected from tree pollen, weed pollen, grass pollen, and mold spores. 78. The method according to claim 75, wherein the perennial allergic conjunctivitis is caused by or partially by a perennial allergen. 79. The method according to claim 78, wherein the perennial allergen is at least one selected from dust mites, cockroaches, and animal dander.80. The method of claim 75, wherein the vernal keratoconjunctivitis is at least one selected from eyelid vernal keratoconjunctivitis, limbal vernal keratoconjunctivitis, and mixed vernal keratoconjunctivitis. 81. The method of claim 75, wherein the giant papillary conjunctivitis is caused, or is partially caused, by repetitive mechanical irritation of the conjunctiva. 82. The method of claim 81, wherein the repetitive mechanical irritation of the conjunctiva is associated with at least one selected from contact lens wear, use of ocular prostheses, use of conjunctival sutures, use of prominent scleral buckles, and corneal scarring. 83. The method of claim 75, wherein the atopic keratoconjunctivitis is accompanied by atopic dermatitis and / or asthma. 84. The method of claim 75, wherein the vesicular keratoconjunctivitis is caused, or is partially caused, by delayed hypersensitivity or inflammatory reactions of the cornea and conjunctiva to antigens expressed by various pathogens. 85. The method of claim 84, wherein the pathogen is at least one selected from bacteria (e.g., Staphylococcus aureus, Streptococcus viridans, Mycobacterium tuberculosis), viruses (e.g., herpes simplex virus), chlamydia, fungi (e.g., Candida albicans), and parasites (e.g., tapeworms such as Hymenolepis microsporum; and nematodes). 86. The method of any one of claims 68 to 85, wherein the subject does not suffer from any ocular disease selected from viral conjunctivitis, bacterial conjunctivitis, chemical conjunctivitis, and dry eye syndrome or dry eye-related conditions. 87. The method of any one of claims 68 to 86, wherein the subject experiences at least one symptom prior to administration of the artificial polypeptide of formula (IV), the symptom being selected from conjunctival redness, conjunctival edema, conjunctival hyperemia, eyelid redness, eyelid edema, eyelid hyperemia, itchy eyes, visible corneal damage, mucus secretion, watery secretion, tearing, photophobia, foreign body sensation, and difficulty opening the eyes. 88. The method according to any one of claims 68 to 87, wherein the subject, after administration of at least one dose of the artificial polypeptide of formula (IV), shows relief of at least one symptom selected from conjunctival redness, conjunctival edema, conjunctival hyperemia, eyelid redness, eyelid edema, eyelid hyperemia, itchy eyes, visible corneal damage, mucus secretion, watery secretion, tearing, photophobia, foreign body sensation, and difficulty opening the eyes. 89. The method according to any one of claims 68 to 88, wherein the subject, after administration of at least one dose of the artificial polypeptide of formula (IV), shows improvement in at least one tissue selected from the conjunctiva, cornea, anterior chamber, iris, pupil, vitreous body, and fundus.90. A method for treating or preventing allergic conjunctivitis in a subject in need, comprising administering to said subject an effective amount of an artificial polypeptide of formula (V): AX-Y(V), wherein X is a portion comprising a sequence having at least 80% identity with SEQ ID NO: 1, and Y is a portion comprising 10 to 30 amino acids, wherein Y comprises a sequence having at least 10 consecutive AAs as in SEQ ID NO: 2. 91. The method of claim 90, wherein Y comprises 10 to 25 amino acids, Y comprises 10 to 20 amino acids, or Y comprises 10 to 15 amino acids. 92. The method of claim 90 or 91, wherein X comprises a sequence having at least 90% identity with SEQ ID NO: 1, X comprises a sequence having at least 95% identity with SEQ ID NO: 1, or X comprises the sequence of SEQ ID NO: 1. 93. The method according to any one of claims 90 to 92, wherein at least 50% of the amino acids in X are selected from R, K, N, D, Q, E, and H. 94. The method according to any one of claims 90 to 93, wherein X comprises a sequence having at least 80% identity with SEQ ID NO: 96, X comprises a sequence having at least 90% identity with SEQ ID NO: 96, X comprises a sequence having at least 95% identity with SEQ ID NO: 96, or X comprises the sequence of SEQ ID NO: 96. 95. The method according to any one of claims 90 to 94, wherein Y comprises a sequence having at most 80% identity with SEQ ID NO: 2, Y comprises a sequence having at most 70% identity with SEQ ID NO: 2, or Y comprises a sequence having at most 50% identity with SEQ ID NO: 2. 96. The method according to any one of claims 90 to 95, wherein Y comprises a sequence having at least 80% identity with any one of SEQ ID NO: 97-103, Y comprises a sequence having at least 90% identity with any one of SEQ ID NO: 97-103, Y comprises a sequence having at least 95% identity with any one of SEQ ID NO: 97-103, or Y comprises a sequence selected from any one of SEQ ID NO: 97-103. 97. The method according to any one of claims 90 to 96, wherein the polypeptide comprises a sequence having at least 90% identity with any one of SEQ ID NO: 53-56 and 104-110.98. The method of any one of claims 90 to 97, wherein the allergic conjunctivitis is at least one selected from seasonal allergic conjunctivitis, perennial allergic conjunctivitis, vernal keratoconjunctivitis, giant papillary conjunctivitis, atopic keratoconjunctivitis, and vesicular keratoconjunctivitis. 99. The method of claim 98, wherein the seasonal allergic conjunctivitis is caused by or partially by a seasonal allergen. 100. The method of claim 99, wherein the seasonal allergen is at least one selected from tree pollen, weed pollen, grass pollen, and fungal spores. 101. The method of claim 98, wherein the perennial allergic conjunctivitis is caused by or partially by a perennial allergen. 102. The method of claim 101, wherein the perennial allergen is at least one selected from dust mites, cockroaches, and animal dander. 103. The method of claim 98, wherein the vernal keratoconjunctivitis is at least one selected from eyelid vernal keratoconjunctivitis, limbal vernal keratoconjunctivitis, and mixed vernal keratoconjunctivitis. 104. The method of claim 98, wherein the giant papillary conjunctivitis is caused, or is partially caused, by repetitive mechanical irritation of the conjunctiva. 105. The method of claim 104, wherein the repetitive mechanical irritation of the conjunctiva is associated with at least one selected from the following: wearing contact lenses, using ocular prostheses, using conjunctival sutures, using scleral buckles, and corneal scarring. 106. The method of claim 98, wherein the atopic keratoconjunctivitis is accompanied by atopic dermatitis and / or asthma. 107. The method of claim 98, wherein the herpetic keratoconjunctivitis is caused, or is partially caused, by delayed hypersensitivity or inflammatory reactions of the cornea and conjunctiva to antigens expressed by various pathogens. 108. The method of claim 107, wherein the pathogen is at least one selected from bacteria (e.g., Staphylococcus aureus, Streptococcus viridans, Mycobacterium tuberculosis), viruses (e.g., herpes simplex virus), chlamydia, fungi (e.g., Candida albicans), and parasites (e.g., tapeworms such as Hymenolepis microsporum; and nematodes). 109. The method of any one of claims 90 to 108, wherein the subject does not suffer from any ocular disease selected from viral conjunctivitis, bacterial conjunctivitis, chemical conjunctivitis, and dry eye syndrome or dry eye-related conditions.110. The method according to any one of claims 90 to 109, wherein the subject experiences at least one symptom prior to administration of the artificial polypeptide of formula (V), the symptom being selected from conjunctival redness, conjunctival edema, conjunctival hyperemia, eyelid redness, eyelid edema, eyelid hyperemia, itchy eyes, visible corneal damage, mucus secretion, watery secretion, tearing, photophobia, foreign body sensation, and difficulty opening the eyes. 111. The method according to any one of claims 90 to 110, wherein the subject, after administration of at least one dose of the artificial polypeptide of formula (V), shows a reduction in at least one symptom selected from conjunctival redness, conjunctival edema, conjunctival hyperemia, eyelid redness, eyelid edema, eyelid hyperemia, itchy eyes, visible corneal damage, mucus secretion, watery secretion, tearing, photophobia, foreign body sensation, and difficulty opening the eyes. 112. The method according to any one of claims 90 to 111, wherein the subject shows improvement in at least one tissue selected from the conjunctiva, cornea, anterior chamber, iris, pupil, vitreous body, and fundus after administration of at least one dose of the artificial polypeptide of formula (V). 113. A method for treating or preventing allergic conjunctivitis in a subject in need, comprising administering to the subject an effective amount of the artificial polypeptide of formula (VI): X-Y (VI), wherein X is a portion comprising a mutant of sequence SEQ ID NO: 1, characterized in that the mutant mutates at least 1, 2, 3, 4, 5, 6, 7, 8, or 9 Ds in SEQ ID NO: 1 to S, and / or mutates at least 1, 2, 3, 4, 5, or 6 Es in SEQ ID NO: 1 to T; and Y is a portion comprising a mutant of sequence SEQ ID NO: 2, characterized in that the mutant mutates at least 1, 2, 3, 4, or 5 Cs in SEQ ID NO: 2 to A. 114. The method of claim 113, wherein X comprises a sequence having at least 70% identity with SEQ ID NO: 1, and / or X comprises a sequence having at most 95% identity with SEQ ID NO: 1. 115. The method of claim 113 or 114, wherein Y comprises a sequence having at least 80% identity with SEQ ID NO: 2, and / or Y comprises a sequence having at most 95% identity with SEQ ID NO: 2. 116. The method of any one of claims 113 to 115, wherein at least 50% of the amino acids in Y are selected from I, V, L, F, C, M, and A. 117. The method of any one of claims 113 to 116, wherein the total number of R, K, T, A, N, Q, D, E, S, and G in X is greater than 30, and / or the total number of W, Y, F, M, L, I, and V in X does not exceed 20.118. The method according to any one of claims 113 to 117, wherein the total number of R, K, T, A, N, Q, D, E, S, and G in Y is greater than 10, and / or the total number of W, Y, F, M, L, I, and V in Y does not exceed 20. Claims 8 / 20, page 9, CN 121079312 A 119. The method according to any one of claims 113 to 118, wherein X comprises a sequence having at least 80% identity with any one of SEQ ID NO: 80-83, X comprises a sequence selected from SEQ ID NO: 80-83, or X is a sequence selected from SEQ ID NO: 80-83. 120. The method according to any one of claims 113 to 119, wherein Y comprises a sequence having at least 80% identity with SEQ ID NO: 3, Y comprises a sequence of SEQ ID NO: 3, or Y is a sequence of SEQ ID NO: 3. 121. The method of any one of claims 113 to 120, wherein the artificial polypeptide comprises a sequence having at least 80% identity with any one of SEQ ID NO: 90-93, the artificial polypeptide comprising a sequence selected from any one of SEQ ID NO: 90-93, or the artificial polypeptide is a sequence selected from any one of SEQ ID NO: 90-93. 122. The method of any one of claims 113 to 121, wherein the allergic conjunctivitis is at least one selected from seasonal allergic conjunctivitis, perennial allergic conjunctivitis, vernal keratoconjunctivitis, giant papillary conjunctivitis, atopic keratoconjunctivitis, and herpetic keratoconjunctivitis. 123. The method of claim 122, wherein the seasonal allergic conjunctivitis is caused by or partially by a seasonal allergen. 124. The method of claim 123, wherein the seasonal allergen is at least one selected from tree pollen, weed pollen, grass pollen, and mold spores. 125. The method of claim 122, wherein the perennial allergic conjunctivitis is caused by or partially by a perennial allergen. 126. The method of claim 125, wherein the perennial allergen is at least one selected from dust mites, cockroaches, and animal dander. 127. The method of claim 122, wherein the vernal keratoconjunctivitis is at least one selected from eyelid vernal keratoconjunctivitis, limbal vernal keratoconjunctivitis, and mixed vernal keratoconjunctivitis. 128. The method of claim 122, wherein the giant papillary conjunctivitis is caused by or partially by repeated mechanical irritation of the conjunctiva.129. The method of claim 128, wherein the repetitive mechanical stimulation of the conjunctiva is associated with at least one selected from contact lens wear, use of ocular prostheses, use of conjunctival sutures, use of scleral buckles, and corneal scarring. 130. The method of claim 122, wherein the atopic keratoconjunctivitis is accompanied by atopic dermatitis and / or asthma. 131. The method of claim 122, wherein the herpetic keratoconjunctivitis is caused by or in part by a delayed-type hypersensitivity or inflammatory response of the cornea and conjunctiva to antigens expressed by various pathogens. 132. The method of claim 131, wherein the pathogen is at least one selected from bacteria (e.g., Staphylococcus aureus, Streptococcus viridans, Mycobacterium tuberculosis), viruses (e.g., herpes simplex virus), chlamydia, fungi (e.g., Candida albicans), and parasites (e.g., tapeworms such as Hymenolepis microsporum; and nematodes). 133. The method according to any one of claims 113 to 132, wherein the subject does not suffer from any eye disease selected from viral conjunctivitis, bacterial conjunctivitis, chemical conjunctivitis, and dry eye syndrome or dry eye-related conditions. 134. The method according to any one of claims 113 to 133, wherein the subject experiences at least one symptom prior to administration of the artificial polypeptide of formula (VI), the symptom being selected from conjunctival redness, conjunctival edema, conjunctival hyperemia, eyelid redness, eyelid edema, eyelid hyperemia, itchy eyes, visible corneal damage, mucus secretion, watery secretion, tearing, photophobia, foreign body sensation, and difficulty opening the eyes. (Claims 9 / 20 pages 10 CN 121079312 A) 135. The method according to any one of claims 113 to 134, wherein the subject, after administration of at least one dose of the artificial polypeptide of formula (VI), exhibits a reduction in at least one symptom selected from conjunctival redness, conjunctival edema, conjunctival hyperemia, eyelid redness, eyelid edema, eyelid hyperemia, itchy eyes, visible corneal damage, mucus secretion, watery secretion, tearing, photophobia, foreign body sensation, and difficulty opening the eyes. 136. The method according to any one of claims 113 to 135, wherein the subject, after administration of at least one dose of the artificial polypeptide of formula (VI), exhibits improvement in at least one tissue selected from the conjunctiva, cornea, anterior chamber, iris, pupil, vitreous body, and fundus.137. A method for treating or preventing allergic conjunctivitis in a subject in need, comprising administering to the subject an effective amount of an artificial polypeptide of formula (VII): X-Y (VII), wherein X is a portion comprising a mutant of the sequence SEQ ID NO: 1, characterized in that the mutant has an insertion of at least 1, 2, 3, 4, or 5 amino acids relative to SEQ ID NO: 1, and Y is a portion comprising 10 to 30 amino acids, wherein Y comprises a sequence having at least 15 consecutive amino acids of SEQ ID NO: 2. 138. The method of claim 137, wherein the amino acid insertion is located at the N-terminus of X, and / or the inserted amino acid is M. 139. The method according to claim 137 or 138, wherein Y is a portion comprising a mutant of sequence SEQ ID NO: 2, characterized in that the mutant has a truncation of at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acids relative to SEQ ID NO: 2, and optionally, the truncation of at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acids is located at the C-terminus of Y. 140. The method according to any one of claims 137 to 139, wherein at least 50% of the amino acids in X are selected from R, K, N, D, Q, E, and H, and / or at most 60% of the amino acids in X are selected from R, K, N, D, Q, E, and H. 141. The method according to any one of claims 137 to 140, wherein the total number of E or D in X is at least 8, and / or the total number of E or D in X is at most 15. 142. The method according to any one of claims 137 to 141, wherein the total number of R, K, T, A, N, Q, D, E, S, and G in X is greater than 30, and / or the total number of W, Y, F, M, L, I, and V in X does not exceed 20. 143. The method according to any one of claims 137 to 142, wherein Y comprises 15 to 25 amino acids, Y comprises 18 to 25 amino acids, or Y comprises 20 to 25 amino acids. 144. The method according to any one of claims 137 to 143, wherein 40-65% of the amino acids in Y are selected from I, V, L, F, C, M, and A. 145. The method according to any one of claims 137 to 144, wherein the total number of R, K, T, A, N, Q, D, E, S and G in Y does not exceed 10, and / or the total number of W, Y, F, M, L, I and V in Y does not exceed 15.146. The method of any one of claims 137 to 145, wherein X comprises a sequence having at least 80% identity with SEQ ID NO: 96, X comprises a sequence of SEQ ID NO: 96, or X is a sequence of SEQ ID NO: 96. 147. The method of any one of claims 137 to 146, wherein Y comprises a sequence having at least 80% identity with any one of SEQ ID NO: 97-103, Y comprises a sequence of any one of SEQ ID NO: 97-103, or Y is a sequence of any one of SEQ ID NO: 97-103. 148. The method according to any one of claims 137 to 147, wherein the artificial polypeptide comprises a sequence having at least 80% identity with any one of SEQ ID NO: 104-110, the artificial polypeptide comprising any one of SEQ ID NO: 104-110, or the artificial polypeptide is any one of SEQ ID NO: 104-110. 149. The method according to any one of claims 137 to 148, wherein the allergic conjunctivitis is at least one selected from seasonal allergic conjunctivitis, perennial allergic conjunctivitis, vernal keratoconjunctivitis, giant papillary conjunctivitis, atopic keratoconjunctivitis, and herpetic keratoconjunctivitis. 150. The method according to claim 149, wherein the seasonal allergic conjunctivitis is caused by or partially by a seasonal allergen. 151. The method of claim 150, wherein the seasonal allergen is at least one selected from tree pollen, weed pollen, grass pollen, and fungal spores. 152. The method of claim 149, wherein the perennial allergic conjunctivitis is caused by or partially by a perennial allergen. 153. The method of claim 152, wherein the perennial allergen is at least one selected from dust mites, cockroaches, and animal dander. 154. The method of claim 149, wherein the vernal keratoconjunctivitis is at least one selected from eyelid vernal keratoconjunctivitis, limbal vernal keratoconjunctivitis, and mixed vernal keratoconjunctivitis. 155. The method of claim 149, wherein the giant papillary conjunctivitis is caused by or partially by repetitive mechanical irritation of the conjunctiva. 156. The method of claim 155, wherein the repetitive mechanical irritation of the conjunctiva is associated with at least one selected from contact lens wear, use of ocular prostheses, use of conjunctival sutures, use of prominent scleral buckles, and corneal scarring.157. The method of claim 149, wherein the atopic keratoconjunctivitis is accompanied by atopic dermatitis and / or asthma. 158. The method of claim 149, wherein the herpetic keratoconjunctivitis is caused, or is partially caused, by a delayed-type hypersensitivity or inflammatory response of the cornea and conjunctiva to antigens expressed by various pathogens. 159. The method of claim 158, wherein the pathogen is at least one selected from bacteria (e.g., Staphylococcus aureus, Streptococcus viridans, Mycobacterium tuberculosis), viruses (e.g., herpes simplex virus), chlamydia, fungi (e.g., Candida albicans), and parasites (e.g., tapeworms such as Hymenolepis microsporum; and nematodes). 160. The method of any one of claims 137 to 159, wherein the subject does not suffer from any ocular disease selected from viral conjunctivitis, bacterial conjunctivitis, chemical conjunctivitis, and dry eye syndrome or dry eye-related conditions. 161. The method according to any one of claims 137 to 160, wherein the subject experiences at least one symptom prior to administration of the artificial polypeptide of formula (VII), the symptom being selected from conjunctival redness, conjunctival edema, conjunctival hyperemia, eyelid redness, eyelid edema, eyelid hyperemia, itchy eyes, visible corneal damage, mucus secretion, watery secretion, tearing, photophobia, foreign body sensation, and difficulty opening the eyes. 162. The method according to any one of claims 137 to 161, wherein the subject, after administration of at least one dose of the artificial polypeptide of formula (VII), shows a reduction in at least one symptom selected from conjunctival redness, conjunctival edema, conjunctival hyperemia, eyelid redness, eyelid edema, eyelid hyperemia, itchy eyes, visible corneal damage, mucus secretion, watery secretion, tearing, photophobia, foreign body sensation, and difficulty opening the eyes. 163. The method according to any one of claims 137 to 162, wherein the subject shows improvement in at least one tissue selected from the conjunctiva, cornea, anterior chamber, iris, pupil, vitreous body and fundus after administration of at least one dose of the artificial polypeptide of formula (VII) of claim 11 / 20 pages 12 CN 121079312 A. 164. A method for treating or preventing allergic conjunctivitis in a subject in need, comprising administering to the subject an effective amount of a mutant of an artificial polypeptide of formula (I), X-Y (I), wherein X is a portion comprising a sequence having at least 80% identity with SEQ ID NO: 1, Y is a portion comprising 10 to 50 amino acids, at least 50% of said amino acids being selected from I, V, L, F, C, M, and A, and Y comprising a total number of less than 5 cysteine ​​(C) residues, characterized in that the mutant mutates at least 1, 2, 3, 4, 5, 6, 7, 8, or 9 D residues in X to S residues, and / or mutates at least 1, 2, 3, 4, 5, or 6 E residues in X to T residues.165. The method of claim 164, wherein at least 20% of the amino acids in X are selected from R, K, N, D, Q, E, and H; at least 30% of the amino acids in X are selected from R, K, N, D, Q, E, and H; at most 90% of the amino acids in X are selected from R, K, N, D, Q, E, and H; and / or at most 80% of the amino acids in X are selected from R, K, N, D, Q, E, and H. 166. The method of claim 164 or 165, wherein X comprises a sequence having at least 70% identity with SEQ ID NO: 1. 167. The method of any one of claims 164 to 166, wherein Y comprises a total number of less than 4 cysteine ​​(C) residues, or Y comprises a total number of less than 3 cysteine ​​(C) residues. 168. The method according to any one of claims 164 to 167, wherein the total number of hydrophobic amino acids in Y is greater than 8, the total number of hydrophobic amino acids in Y is greater than 12, the total number of hydrophobic amino acids in Y is greater than 15, and / or the total number of hydrophilic amino acids in Y does not exceed 5. 169. The method according to any one of claims 164 to 168, wherein Y comprises a sequence having at least 90% identity with any one of SEQ ID NO: 3-15, 58-61, and 84-85, or Y comprises a sequence having at least 90% identity with any one of SEQ ID NO: 3-18, 58-61, and 84-85. 170. The method according to any one of claims 164 to 169, wherein the allergic conjunctivitis is at least one selected from seasonal allergic conjunctivitis, perennial allergic conjunctivitis, vernal keratoconjunctivitis, giant papillary conjunctivitis, atopic keratoconjunctivitis, and herpetic keratoconjunctivitis. 171. The method of claim 170, wherein the seasonal allergic conjunctivitis is caused by or partially by a seasonal allergen. 172. The method of claim 171, wherein the seasonal allergen is at least one selected from tree pollen, weed pollen, grass pollen, and mold spores. 173. The method of claim 170, wherein the perennial allergic conjunctivitis is caused by or partially by a perennial allergen. 174. The method of claim 173, wherein the perennial allergen is at least one selected from dust mites, cockroaches, and animal dander. 175. The method of claim 170, wherein the vernal keratoconjunctivitis is at least one selected from eyelid vernal keratoconjunctivitis, limbal vernal keratoconjunctivitis, and mixed vernal keratoconjunctivitis. 176. The method of claim 170, wherein the giant papillary conjunctivitis is caused by or partially by repeated mechanical irritation of the conjunctiva.177. The method of claim 176, wherein the repetitive mechanical stimulation of the conjunctiva is associated with at least one selected from the following: wearing contact lenses, using ocular prostheses, using conjunctival sutures, using scleral buckles, and corneal scarring. 178. The method of claim 170, wherein the atopic keratoconjunctivitis is accompanied by atopic dermatitis and / or asthma. 179. The method of claim 170, wherein the herpetic keratoconjunctivitis is caused, or in part, by delayed hypersensitivity or inflammatory reactions of the cornea and conjunctiva to antigens expressed by various pathogens. 180. The method of claim 179, wherein the pathogen is at least one selected from bacteria (e.g., Staphylococcus aureus, Streptococcus viridans, Mycobacterium tuberculosis), viruses (e.g., herpes simplex virus), chlamydia, fungi (e.g., Candida albicans), and parasites (e.g., tapeworms such as Hymenolepis microsporum; and nematodes). 181. The method of any one of claims 164 to 180, wherein the subject does not suffer from any eye disease selected from viral conjunctivitis, bacterial conjunctivitis, chemical conjunctivitis, and dry eye syndrome or dry eye-related conditions. 182. The method of any one of claims 164 to 181, wherein the subject experiences at least one symptom prior to administration of the mutant of the artificial polypeptide of formula (I), the symptom being selected from conjunctival redness, conjunctival edema, conjunctival hyperemia, eyelid redness, eyelid edema, eyelid hyperemia, itchy eyes, visible corneal damage, mucus secretion, watery secretion, tearing, photophobia, foreign body sensation, and difficulty opening the eyes. 183. The method according to any one of claims 164 to 182, wherein the subject, after administration of at least one dose of the mutant of the artificial polypeptide of formula (I), exhibits a reduction in at least one symptom selected from conjunctival redness, conjunctival edema, conjunctival hyperemia, eyelid redness, eyelid edema, eyelid hyperemia, itchy eyes, visible corneal damage, mucus secretion, watery secretion, tearing, photophobia, foreign body sensation, and difficulty opening the eyes. 184. The method according to any one of claims 164 to 183, wherein the subject, after administration of at least one dose of the mutant of the artificial polypeptide of formula (I), exhibits improvement in at least one tissue selected from the conjunctiva, cornea, anterior chamber, iris, pupil, vitreous body, and fundus.185. A method for treating or preventing allergic conjunctivitis in a subject in need, comprising administering to the subject an effective amount of a mutant of an artificial polypeptide of formula (II), X-Y (II), wherein X is a portion comprising a sequence having at least 80% identity with SEQ ID NO: 1, Y is a portion comprising 10 to 50 amino acids, at least 50% of said amino acids being selected from I, V, L, F, C, M, and A, and Y comprising a sequence having at most 90% identity with SEQ ID NO: 2, characterized in that the mutant mutates at least 1, 2, 3, 4, 5, 6, 7, 8, or 9 Ds in X to S, and / or mutates at least 1, 2, 3, 4, 5, or 6 Es in X to T. 186. The method of claim 185, wherein at least 20% of the amino acids in X are selected from R, K, N, D, Q, E, and H; at least 30% of the amino acids in X are selected from R, K, N, D, Q, E, and H; at most 90% of the amino acids in X are selected from R, K, N, D, Q, E, and H; and / or at most 80% of the amino acids in X are selected from R, K, N, D, Q, E, and H. 187. The method of claim 185 or 186, wherein X comprises a sequence having at least 70% identity with SEQ ID NO: 1. 188. The method of any one of claims 185 to 187, wherein Y comprises a sequence having at most 80% identity with SEQ ID NO: 2, or Y comprises a sequence having at most 70% identity with SEQ ID NO: 2. 189. The method according to any one of claims 185 to 188, wherein the total number of hydrophobic amino acids in Y is greater than 8, the total number of hydrophobic amino acids in Y is greater than 12, the total number of hydrophobic amino acids in Y is greater than 15, and / or the total number of hydrophilic amino acids in Y does not exceed 5. 190. The method according to any one of claims 185 to 189, wherein Y comprises a sequence having at least 90% identity with any one of SEQ ID NO: 16-18, or Y comprises a sequence having at least 95% identity with any one of SEQ ID NO: 16-18. 191. The method according to any one of claims 185 to 190, wherein the allergic conjunctivitis is at least one selected from seasonal allergic conjunctivitis, perennial allergic conjunctivitis, vernal keratoconjunctivitis, giant papillary conjunctivitis, atopic keratoconjunctivitis, and herpetic keratoconjunctivitis. 192. The method of claim 191, wherein the seasonal allergic conjunctivitis is caused by or in part by a seasonal allergen. 193. The method of claim 192, wherein the seasonal allergen is at least one selected from tree pollen, weed pollen, grass pollen, and mold spores.194. The method of claim 191, wherein the perennial allergic conjunctivitis is caused by or partially by a perennial allergen. 195. The method of claim 194, wherein the perennial allergen is at least one selected from dust mites, cockroaches, and animal dander. 196. The method of claim 191, wherein the vernal keratoconjunctivitis is at least one selected from eyelid vernal keratoconjunctivitis, limbal vernal keratoconjunctivitis, and mixed vernal keratoconjunctivitis. 197. The method of claim 191, wherein the giant papillary conjunctivitis is caused by or partially by repetitive mechanical irritation of the conjunctiva. 198. The method of claim 197, wherein the repetitive mechanical irritation of the conjunctiva is associated with at least one selected from contact lens wear, use of ocular prostheses, use of conjunctival sutures, use of prominent scleral buckles, and corneal scarring. 199. The method of claim 191, wherein the atopic keratoconjunctivitis is accompanied by atopic dermatitis and / or asthma. 200. The method of claim 191, wherein the herpetic keratoconjunctivitis is caused, or is partially caused, by a delayed-type hypersensitivity reaction or inflammatory reaction of the cornea and conjunctiva to antigens expressed by various pathogens. 201. The method of claim 200, wherein the pathogen is at least one selected from bacteria (e.g., Staphylococcus aureus, Streptococcus viridans, Mycobacterium tuberculosis), viruses (e.g., herpes simplex virus), chlamydia, fungi (e.g., Candida albicans), and parasites (e.g., tapeworms such as Hymenolepis microsporum; and nematodes). 202. The method of any one of claims 185 to 201, wherein the subject does not suffer from any ocular disease selected from viral conjunctivitis, bacterial conjunctivitis, chemical conjunctivitis, and dry eye syndrome or dry eye-related conditions. 203. The method according to any one of claims 185 to 202, wherein the subject experiences at least one symptom prior to administration of the mutant of the artificial polypeptide of formula (II), the symptom being selected from conjunctival redness, conjunctival edema, conjunctival hyperemia, eyelid redness, eyelid edema, eyelid hyperemia, itchy eyes, visible corneal damage, mucus secretion, watery secretion, tearing, photophobia, foreign body sensation, and difficulty opening the eyes. 204. The method according to any one of claims 185 to 203, wherein the subject, after administration of at least one dose of the mutant of the artificial polypeptide of formula (II), shows a reduction in at least one symptom selected from conjunctival redness, conjunctival edema, conjunctival hyperemia, eyelid redness, eyelid edema, eyelid hyperemia, itchy eyes, visible corneal damage, mucus secretion, watery secretion, tearing, photophobia, foreign body sensation, and difficulty opening the eyes.Claims 14 / 20 pages 15 CN 121079312 A 205. The method according to any one of claims 185 to 204, wherein the subject shows improvement in at least one tissue selected from the conjunctiva, cornea, anterior chamber, iris, pupil, vitreous body and fundus after administration of at least one dose of the mutant of the formula (II) artificial polypeptide. 206. A method for treating or preventing allergic conjunctivitis in a subject in need, comprising administering to the subject an effective amount of a mutant of an artificial polypeptide of formula (III), X-Y(III), wherein X is a portion comprising 40 to 65 amino acids, at least 50% of which are selected from H, R, K, D, Q, N, and E, Y is a portion comprising a sequence having at least 80% identity with SEQ ID NO: 2, and the total number of H, R, K, D, Q, N, and E in X is less than 33, characterized in that the mutant mutates at least 1, 2, 3, 4, 5, 6, 7, 8, or 9 Ds in X to S, and / or mutates at least 1, 2, 3, 4, 5, or 6 Es in X to T. 207. The method of claim 206, wherein at least 20% of the amino acids in X are selected from R, K, N, D, Q, E, and H; at least 30% of the amino acids in X are selected from R, K, N, D, Q, E, and H; at most 90% of the amino acids in X are selected from R, K, N, D, Q, E, and H; and / or at most 80% of the amino acids in X are selected from R, K, N, D, Q, E, and H. 208. The method of claim 206 or 207, wherein X comprises a sequence having at least 70% identity with SEQ ID NO: 1. 209. The method of any one of claims 206 to 208, wherein Y comprises a sequence having at least 90% identity with SEQ ID NO: 2, or Y comprises the sequence of SEQ ID NO: 2. 210. The method of any one of claims 206 to 209, wherein at least 50% of the amino acids in Y are selected from I, V, L, F, C, M, and A. 211. The method according to any one of claims 206 to 210, wherein the total number of H, R, K, D, Q, N, and E in X is less than 30, the total number of H, R, K, D, Q, N, and E in X is less than 25, or the total number of H, R, K, D, Q, N, and E in X is less than 20. 212. The method according to any one of claims 206 to 211, wherein the total number of hydrophilic amino acids in X is greater than 10, the total number of hydrophilic amino acids in X is greater than 15, the total number of hydrophilic amino acids in X is greater than 20, the total number of hydrophilic amino acids in X is greater than 25, the total number of hydrophobic amino acids in X is not more than 15, and / or the total number of hydrophobic amino acids in X is not more than 10.213. The method of any one of claims 206 to 212, wherein the allergic conjunctivitis is at least one selected from seasonal allergic conjunctivitis, perennial allergic conjunctivitis, vernal keratoconjunctivitis, giant papillary conjunctivitis, atopic keratoconjunctivitis, and herpetic keratoconjunctivitis. 214. The method of claim 213, wherein the seasonal allergic conjunctivitis is caused by or partially by a seasonal allergen. 215. The method of claim 214, wherein the seasonal allergen is at least one selected from tree pollen, weed pollen, grass pollen, and fungal spores. 216. The method of claim 213, wherein the perennial allergic conjunctivitis is caused by or partially by a perennial allergen. 217. The method of claim 216, wherein the perennial allergen is at least one selected from dust mites, cockroaches, and animal dander. 218. The method of claim 213, wherein the vernal keratoconjunctivitis is at least one selected from eyelid vernal keratoconjunctivitis, limbal vernal keratoconjunctivitis, and mixed vernal keratoconjunctivitis. 219. The method of claim 213, wherein the giant papillary conjunctivitis is caused by or in part by repetitive mechanical stimulation of the conjunctiva. 220. The method of claim 219, wherein the repetitive mechanical stimulation of the conjunctiva is associated with at least one selected from contact lens wear, use of ocular prostheses, use of conjunctival sutures, use of prominent scleral buckles, and corneal scarring. 221. The method of claim 213, wherein the atopic keratoconjunctivitis is accompanied by atopic dermatitis and / or asthma. 222. The method of claim 213, wherein the vesicular keratoconjunctivitis is caused by or in part by delayed hypersensitivity or inflammatory reactions of the cornea and conjunctiva to antigens expressed by various pathogens. 223. The method of claim 222, wherein the pathogen is at least one selected from bacteria (e.g., Staphylococcus aureus, Streptococcus viridans, Mycobacterium tuberculosis), viruses (e.g., herpes simplex virus), chlamydia, fungi (e.g., Candida albicans), and parasites (e.g., tapeworms such as Hymenolepis microsporum; and nematodes). 224. The method of any one of claims 206 to 223, wherein the subject does not suffer from any ocular disease selected from viral conjunctivitis, bacterial conjunctivitis, chemical conjunctivitis, and dry eye syndrome or dry eye-related conditions.225. The method according to any one of claims 206 to 224, wherein the subject experiences at least one symptom prior to administration of the mutant of the artificial polypeptide of formula (III), the symptom being selected from conjunctival redness, conjunctival edema, conjunctival hyperemia, eyelid redness, eyelid edema, eyelid hyperemia, itchy eyes, visible corneal damage, mucus secretion, watery secretion, tearing, photophobia, foreign body sensation, and difficulty opening the eyes. 226. The method according to any one of claims 206 to 225, wherein the subject, after administration of at least one dose of the mutant of the artificial polypeptide of formula (III), shows a reduction in at least one symptom selected from conjunctival redness, conjunctival edema, conjunctival hyperemia, eyelid redness, eyelid edema, eyelid hyperemia, itchy eyes, visible corneal damage, mucus secretion, watery secretion, tearing, photophobia, foreign body sensation, and difficulty opening the eyes. 227. The method according to any one of claims 206 to 226, wherein the subject shows improvement in at least one tissue selected from the conjunctiva, cornea, anterior chamber, iris, pupil, vitreous body, and fundus after administration of at least one dose of the mutant of the formula (III) artificial polypeptide. 228. A method for treating or preventing allergic conjunctivitis in a subject in need, comprising administering to the subject an effective amount of a mutant of the formula (IV) artificial polypeptide, X-Y (IV), wherein X is a portion comprising 40 to 65 amino acids, at least 50% of which are selected from H, R, K, D, Q, N, and E, Y is a portion comprising a sequence having at least 80% identity with SEQ ID NO: 2, and X comprises a sequence having at most 90% identity with SEQ ID NO: 1, characterized in that the mutant mutates at least 1, 2, 3, 4, 5, 6, 7, 8, or 9 Ds in X to S, and / or mutates at least 1, 2, 3, 4, 5, or 6 Es in X to T. 229. The method of claim 228, wherein at least 20% of the amino acids in X are selected from R, K, N, D, Q, E, and H; at least 30% of the amino acids in X are selected from R, K, N, D, Q, E, and H; at most 90% of the amino acids in X are selected from R, K, N, D, Q, E, and H; and / or at most 80% of the amino acids in X are selected from R, K, N, D, Q, E, and H. 230. The method of claim 228 or 229, wherein X comprises a sequence having at least 70% identity with SEQ ID NO: 1. 231. The method of any one of claims 228 to 230, wherein Y comprises a sequence having at least 90% identity with SEQ ID NO: 2, or Y comprises the sequence of SEQ ID NO: 2.Claims 16 / 20, page 17, CN 121079312 A 232. The method according to any one of claims 228 to 231, wherein at least 50% of the amino acids in Y are selected from I, V, L, F, C, M, and A. 233. The method according to any one of claims 228 to 232, wherein the total number of hydrophilic amino acids in X is greater than 10, the total number of hydrophilic amino acids in X is greater than 15, the total number of hydrophilic amino acids in X is greater than 20, the total number of hydrophilic amino acids in X is greater than 25, the total number of hydrophobic amino acids in X is not more than 15, and / or the total number of hydrophobic amino acids in X is not more than 10. 234. The method according to any one of claims 228 to 233, wherein the allergic conjunctivitis is at least one selected from seasonal allergic conjunctivitis, perennial allergic conjunctivitis, vernal keratoconjunctivitis, giant papillary conjunctivitis, atopic keratoconjunctivitis, and herpetic keratoconjunctivitis. 235. The method of claim 234, wherein the seasonal allergic conjunctivitis is caused by or partially by a seasonal allergen. 236. The method of claim 235, wherein the seasonal allergen is at least one selected from tree pollen, weed pollen, grass pollen, and mold spores. 237. The method of claim 234, wherein the perennial allergic conjunctivitis is caused by or partially by a perennial allergen. 238. The method of claim 237, wherein the perennial allergen is at least one selected from dust mites, cockroaches, and animal dander. 239. The method of claim 234, wherein the vernal keratoconjunctivitis is at least one selected from eyelid vernal keratoconjunctivitis, limbal vernal keratoconjunctivitis, and mixed vernal keratoconjunctivitis. 240. The method of claim 234, wherein the giant papillary conjunctivitis is caused by or partially by repeated mechanical irritation of the conjunctiva. 241. The method of claim 240, wherein the repetitive mechanical stimulation of the conjunctiva is associated with at least one selected from contact lens wear, use of ocular prostheses, use of conjunctival sutures, use of scleral buckles, and corneal scarring. 242. The method of claim 234, wherein the atopic keratoconjunctivitis is accompanied by atopic dermatitis and / or asthma. 243. The method of claim 234, wherein the herpetic keratoconjunctivitis is caused by or in part by a delayed-type hypersensitivity or inflammatory response of the cornea and conjunctiva to antigens expressed by various pathogens. 244. The method of claim 243, wherein the pathogen is at least one selected from bacteria (e.g., Staphylococcus aureus, Streptococcus viridans, Mycobacterium tuberculosis), viruses (e.g., herpes simplex virus), chlamydia, fungi (e.g., Candida albicans), and parasites (e.g., tapeworms such as Hymenolepis microsporum; and nematodes).245. The method of any one of claims 228 to 244, wherein the subject does not suffer from any eye disease selected from viral conjunctivitis, bacterial conjunctivitis, chemical conjunctivitis, and dry eye syndrome or dry eye-related conditions. 246. The method of any one of claims 228 to 245, wherein the subject experiences at least one symptom prior to administration of the mutant of the formula (IV) artificial polypeptide, the symptom being selected from conjunctival redness, conjunctival edema, conjunctival hyperemia, eyelid redness, eyelid edema, eyelid hyperemia, itchy eyes, visible corneal damage, mucus secretion, watery secretion, tearing, photophobia, foreign body sensation, and difficulty opening the eyes. 247. The method according to any one of claims 228 to 246, wherein the subject, after administration of at least one dose of the mutant of the formula (IV) artificial polypeptide, exhibits a reduction in at least one symptom selected from conjunctival redness, conjunctival edema, conjunctival hyperemia, eyelid redness, eyelid edema, eyelid hyperemia, itchy eyes, visible corneal damage, mucus secretion, watery secretion, tearing, photophobia, foreign body sensation, and difficulty opening the eyes. 248. The method according to any one of claims 228 to 247, wherein the subject, after administration of at least one dose of the mutant of the formula (IV) artificial polypeptide, exhibits improvement in at least one tissue selected from the conjunctiva, cornea, anterior chamber, iris, pupil, vitreous body, and fundus. 249. A method for treating or preventing allergic conjunctivitis in a subject in need, comprising administering to the subject an effective amount of a mutant of an artificial polypeptide of formula (V), X-Y (V), wherein X is a portion comprising a sequence having at least 80% identity with SEQ ID NO: 1, and Y is a portion comprising 10 to 30 amino acids, wherein Y comprises a sequence having at least 10 consecutive AAs of SEQ ID NO: 2, characterized in that the mutant mutates at least 1, 2, 3, 4, 5, 6, 7, 8, or 9 Ds in X to S, and / or mutates at least 1, 2, 3, 4, 5, or 6 Es in X to T. 250. The method of claim 249, wherein at least 20% of the amino acids in X are selected from R, K, N, D, Q, E, and H; at least 30% of the amino acids in X are selected from R, K, N, D, Q, E, and H; at most 90% of the amino acids in X are selected from R, K, N, D, Q, E, and H; and / or at most 80% of the amino acids in X are selected from R, K, N, D, Q, E, and H. 251. The method of claim 249 or 250, wherein Y comprises 10 to 25 amino acids, Y comprises 10 to 20 amino acids, or Y comprises 10 to 15 amino acids. 252. The method of any one of claims 249 to 251, wherein X comprises a sequence having at least 70% identity with SEQ ID NO: 1.253. The method of any one of claims 249 to 252, wherein Y comprises a sequence having at most 80% identity with SEQ ID NO: 2, Y comprises a sequence having at most 70% identity with SEQ ID NO: 2, or Y comprises a sequence having at most 50% identity with SEQ ID NO: 2. 254. The method of any one of claims 249 to 253, wherein the allergic conjunctivitis is at least one selected from seasonal allergic conjunctivitis, perennial allergic conjunctivitis, vernal keratoconjunctivitis, giant papillary conjunctivitis, atopic keratoconjunctivitis, and herpetic keratoconjunctivitis. 255. The method of claim 254, wherein the seasonal allergic conjunctivitis is caused by or partially by a seasonal allergen. 256. The method of claim 255, wherein the seasonal allergen is at least one selected from tree pollen, weed pollen, grass pollen, and mold spores. 257. The method of claim 254, wherein the perennial allergic conjunctivitis is caused by or partially by a perennial allergen. 258. The method of claim 257, wherein the perennial allergen is at least one selected from dust mites, cockroaches, and animal dander. 259. The method of claim 254, wherein the vernal keratoconjunctivitis is at least one selected from eyelid vernal keratoconjunctivitis, limbal vernal keratoconjunctivitis, and mixed vernal keratoconjunctivitis. 260. The method of claim 254, wherein the giant papillary conjunctivitis is caused by or partially by repetitive mechanical irritation of the conjunctiva. 261. The method of claim 260, wherein the repetitive mechanical irritation of the conjunctiva is related to at least one of the following: contact lens wear, use of ocular prostheses, use of conjunctival sutures, use of prominent scleral buckles, and corneal scarring. (Claim 18 / 20, page 19, CN 121079312 A) 262. The method of claim 254, wherein the atopic keratoconjunctivitis is accompanied by atopic dermatitis and / or asthma. 263. The method of claim 254, wherein the herpetic keratoconjunctivitis is caused, or is partially caused, by a delayed-type hypersensitivity or inflammatory response of the cornea and conjunctiva to antigens expressed by various pathogens. 264. The method of claim 263, wherein the pathogen is at least one selected from bacteria (e.g., Staphylococcus aureus, Streptococcus viridans, Mycobacterium tuberculosis), viruses (e.g., herpes simplex virus), chlamydia, fungi (e.g., Candida albicans), and parasites (e.g., tapeworms such as Hymenolepis microsporum; and nematodes).265. The method of any one of claims 249 to 264, wherein the subject does not suffer from any eye disease selected from viral conjunctivitis, bacterial conjunctivitis, chemical conjunctivitis, and dry eye syndrome or dry eye-related conditions. 266. The method of any one of claims 249 to 265, wherein the subject experiences at least one symptom prior to administration of the mutant of the formula (V) artificial polypeptide, the symptom being selected from conjunctival redness, conjunctival edema, conjunctival hyperemia, eyelid redness, eyelid edema, eyelid hyperemia, itchy eyes, visible corneal damage, mucus secretion, watery secretion, tearing, photophobia, foreign body sensation, and difficulty opening the eyes. 267. The method of any one of claims 249 to 266, wherein the subject, after administration of at least one dose of the mutant of the artificial polypeptide of formula (V), exhibits a reduction in at least one symptom selected from conjunctival erythema, conjunctival edema, conjunctival hyperemia, eyelid erythema, eyelid edema, eyelid hyperemia, itchy eyes, visible corneal damage, mucus secretion, watery secretion, tearing, photophobia, foreign body sensation, and difficulty opening the eyes. 268. The method of any one of claims 249 to 267, wherein the subject, after administration of at least one dose of the mutant of the artificial polypeptide of formula (V), exhibits improvement in at least one tissue selected from the conjunctiva, cornea, anterior chamber, iris, pupil, vitreous body, and fundus. 269. A method for treating or preventing allergic conjunctivitis in a subject in need, comprising administering to the subject an effective amount of a polypeptide or a fragment or variant thereof, the polypeptide having at least 70% identity with any one of SEQ ID NO: 28, SEQ ID NO: 57, and 62-74. 270. The method of claim 269, wherein the polypeptide is a polypeptide or fragment or variant of any one of SEQ ID NO: 28, SEQ ID NO: 57, and 62-74, or the polypeptide is the polypeptide of SEQ ID NO: 28. 271. The method of claim 269 or 270, wherein the allergic conjunctivitis is at least one selected from seasonal allergic conjunctivitis, perennial allergic conjunctivitis, vernal keratoconjunctivitis, giant papillary conjunctivitis, atopic keratoconjunctivitis, and herpetic keratoconjunctivitis. 272. The method of claim 271, wherein the seasonal allergic conjunctivitis is caused by or partially by a seasonal allergen. 273. The method of claim 272, wherein the seasonal allergen is at least one selected from tree pollen, weed pollen, grass pollen, and mold spores.274. The method of claim 271, wherein the perennial allergic conjunctivitis is caused by or partially by a perennial allergen. 275. The method of claim 274, wherein the perennial allergen is at least one selected from dust mites, cockroaches, and animal dander. Claims 19 / 20 pages 20 CN 121079312 A 276. The method of claim 271, wherein the vernal keratoconjunctivitis is at least one selected from eyelid vernal keratoconjunctivitis, limbal vernal keratoconjunctivitis, and mixed vernal keratoconjunctivitis. 277. The method of claim 271, wherein the giant papillary conjunctivitis is caused by or partially by repetitive mechanical irritation of the conjunctiva. 278. The method of claim 277, wherein the repetitive mechanical irritation of the conjunctiva is associated with at least one selected from contact lens wear, use of ocular prostheses, use of conjunctival sutures, use of prominent scleral buckles, and corneal scarring. 279. The method of claim 271, wherein the atopic keratoconjunctivitis is accompanied by atopic dermatitis and / or asthma. 280. The method of claim 271, wherein the herpetic keratoconjunctivitis is caused, or is partially caused, by a delayed-type hypersensitivity or inflammatory response of the cornea and conjunctiva to antigens expressed by various pathogens. 281. The method of claim 280, wherein the pathogen is at least one selected from bacteria (e.g., Staphylococcus aureus, Streptococcus viridans, Mycobacterium tuberculosis), viruses (e.g., herpes simplex virus), chlamydia, fungi (e.g., Candida albicans), and parasites (e.g., tapeworms such as Hymenolepis microsporum; and nematodes). 282. The method of any one of claims 269 to 281, wherein the subject does not suffer from any ocular disease selected from viral conjunctivitis, bacterial conjunctivitis, chemical conjunctivitis, and dry eye syndrome or dry eye-related conditions. 283. The method according to any one of claims 269 to 282, wherein the subject experiences at least one symptom prior to administration of the polypeptide or a fragment or variant thereof having at least 70% identity with any one of SEQ ID NO: 28, SEQ ID NO: 57 and 62-74, the symptom being selected from conjunctival redness, conjunctival edema, conjunctival hyperemia, eyelid redness, eyelid edema, eyelid hyperemia, itchy eyes, visible corneal damage, mucus secretion, watery secretion, tearing, photophobia, foreign body sensation, and difficulty opening the eyes.284. The method of any one of claims 269 to 283, wherein the subject, after administration of at least one dose of the polypeptide or a fragment or variant thereof having at least 70% identity with any one of SEQ ID NO: 28, SEQ ID NO: 57, and 62-74, shows relief of at least one symptom selected from conjunctival redness, conjunctival edema, conjunctival hyperemia, eyelid redness, eyelid edema, eyelid hyperemia, itchy eyes, visible corneal damage, mucus secretion, watery secretion, tearing, photophobia, foreign body sensation, and difficulty opening the eyes. 285. The method of any one of claims 269 to 284, wherein the subject, after administration of at least one dose of the polypeptide or a fragment or variant thereof having at least 70% identity with any one of SEQ ID NO: 28, SEQ ID NO: 57, and 62-74, shows improvement in at least one tissue selected from the conjunctiva, cornea, anterior chamber, iris, pupil, vitreous body, and fundus. Claims 20 / 20 Page 21 CN 121079312 A Use of a polypeptide for the prevention or treatment of allergic conjunctivitis Cross-reference

[0001] This application claims priority to PCT application No. PCT / CN2023 / 081353, filed March 14, 2023, the contents of which are incorporated herein by reference in their entirety. Technical Field

[0002] This disclosure provides the use of a polypeptide for the prevention or treatment of allergic conjunctivitis. A method for treating or preventing allergic conjunctivitis in a subject in need is also provided, comprising administering to the subject an effective amount of any of the polypeptides disclosed herein. Background Art

[0003] The conjunctiva is a thin, transparent mucous membrane that covers the inside of the eyelids and the white part of the eyeball (i.e., the sclera). The conjunctiva lubricates the eye by producing small amounts of mucus and tears; in addition, it helps prevent microorganisms from entering the eye and also aids in immune surveillance. Conjunctival diseases are common in various populations, particularly because the surface of the eye is directly exposed to external influencing factors and is easily affected by them.

[0004] Conjunctivitis (also known as "pink eye") is a very common conjunctival condition, an inflammation of the inner surface of the eyelids and the outermost white layer of the eye. Conjunctivitis typically presents with redness and swelling of the conjunctiva, as well as tearing. This condition can be caused by viral infections (i.e., viral conjunctivitis), bacterial infections (i.e., bacterial conjunctivitis), chemical substances (i.e., chemical conjunctivitis), allergens (i.e., allergic conjunctivitis), or autoimmune responses (i.e., autoimmune conjunctivitis, such as Sjögren's syndrome, Schwann-Jones syndrome, and cicatricial pemphigoid).

[0005] Allergic conjunctivitis is reported to be the most common cause of conjunctivitis, affecting approximately 15% to 40% of the population (see Mourad MS, Rihan RA (April 2018). "Prevalence of Different Eye Diseases excluding Refractive Errors Presented at the Outpatient Clinic in Beheira Eye Hospital". The Egyptian Journal of Hospital Medicine. 71 (2): 2484–2489). Allergic conjunctivitis is a group of inflammatory diseases caused by a hypersensitive reaction of the conjunctiva to various allergens. This condition is essentially an immune response of the conjunctiva to various indoor or outdoor allergens (such as pollen, mold spores, dust mites, and pet dander) that enter the eye. Because the eyes are directly exposed to the external environment and are relatively sensitive to various irritants, they are easily affected by allergens. The body releases chemicals, including histamine, which produces inflammation in response to these allergens, and then allergic conjunctivitis develops.

[0006] Although allergic conjunctivitis is not a contagious disease and is not life-threatening, it causes considerable inconvenience to the lives of those affected and can sometimes be difficult to manage. Some common signs and symptoms of allergic conjunctivitis include conjunctival redness, edema or hyperemia, eyelid redness, edema or hyperemia, itchy eyes, visible corneal damage, mucus discharge, watery discharge, tearing, photophobia, foreign body sensation, and difficulty opening the eyes. Other reported symptoms include itchy nose, sneezing, coughing, transient blurred vision, difficulty concentrating, decreased productivity, and fatigue.

[0007] Current clinical care for allergic conjunctivitis includes the use of eye drops or other ophthalmic preparations containing antihistamines, mast cell stabilizers, corticosteroids, and / or immunosuppressants, which help alleviate the signs and symptoms of allergic conjunctivitis. However, these measures suffer from problems such as slow onset of action, limited efficacy and / or duration of effect, induction of ocular complications, poor compliance with treatment instructions (page 1 / 68, 22 CN 121079312 A), inconsistent dosage, and drug abuse. Therefore, the medical community's need for drugs that effectively relieve or treat allergic conjunctivitis remains unmet. Summary of the Invention

[0008] This disclosure provides novel measures for the prevention or treatment of allergic conjunctivitis. Specifically, this disclosure provides the use of a polypeptide for the prevention or treatment of allergic conjunctivitis. A method for treating or preventing allergic conjunctivitis in a subject in need is also provided, comprising administering to the subject an effective amount of any of the polypeptides disclosed herein.

[0009] In one aspect, a method is provided for treating or preventing allergic conjunctivitis in a subject in need, comprising administering to the subject an effective amount of an artificial polypeptide of formula (I): X-Y (I), wherein X is a portion comprising a sequence having at least 80% identity with SEQ ID NO: 1, and Y is a portion comprising 10 to 50 amino acids, at least 50% of which are selected from I, V, L, F, C, M, and A; wherein the total number of cysteine ​​(C) contained in Y is less than 5.

[0010] In some embodiments, X comprises a sequence having at least 90% identity with SEQ ID NO: 1, X comprises a sequence having at least 95% identity with SEQ ID NO: 1, or X comprises the sequence of SEQ ID NO: 1. In some embodiments, X comprises a sequence having at least 90% identity with SEQ ID NO: 1. In some embodiments, X comprises a sequence having at least 95% identity with SEQ ID NO: 1. In some embodiments, X comprises the sequence of SEQ ID NO: 1. In some embodiments, at least 50% of the amino acids in X are selected from R, K, N, D, Q, E, and H. In some embodiments, X contains a sequence having at least 90% identity with any of SEQ ID NO: 81-83.

[0011] In some embodiments, Y contains less than 4 cysteine ​​(C) residues, Y contains less than 3 cysteine ​​(C) residues, or Y contains less than 2 cysteine ​​(C) residues. In some embodiments, Y contains less than 4 cysteine ​​(C) residues. In some embodiments, Y contains less than 3 cysteine ​​(C) residues. In some embodiments, Y contains less than 2 cysteine ​​(C) residues. In some embodiments, Y contains more than 8 hydrophobic amino acids, Y contains more than 12 hydrophobic amino acids, Y contains more than 15 hydrophobic amino acids, and / or Y contains no more than 5 hydrophilic amino acids. In some embodiments, Y contains more than 8 hydrophobic amino acids. In some embodiments, the total number of hydrophobic amino acids in Y is greater than 12. In some embodiments, the total number of hydrophobic amino acids in Y is greater than 15. In some embodiments, the total number of hydrophilic amino acids in Y is no more than 5. In some embodiments, Y contains a sequence having at least 90% identity with any one of SEQ ID NO: 3-15, 58-61, and 84-85, or Y contains a sequence having at least 90% identity with any one of SEQ ID NO: 3-18, 58-61, and 84-85. In some embodiments, Y contains a sequence having at least 90% identity with any one of SEQ ID NO: 3-15, 58-61, and 84-85.In some embodiments, Y comprises a sequence having at least 90% identity with any one of SEQ ID NO: 3-18, 58-61, and 84-85.

[0012] In some embodiments, the polypeptide comprises a sequence having at least 90% identity with any one of SEQ ID NO: 29-41, 54-57, 75, and 91-95.

[0013] In some embodiments, allergic conjunctivitis is at least one of seasonal allergic conjunctivitis, perennial allergic conjunctivitis, vernal keratoconjunctivitis, giant papillary conjunctivitis, atopic keratoconjunctivitis, and herpetic keratoconjunctivitis. In some embodiments, seasonal allergic conjunctivitis is caused by or partially by a seasonal allergen. In some embodiments, the seasonal allergen is at least one of tree pollen, weed pollen, grass pollen, and mold spores. In some embodiments, perennial allergic conjunctivitis is caused by or partially by a perennial allergen. In some embodiments, the perennial allergen is at least one selected from dust mites, cockroaches, and animal dander. In some embodiments, vernal keratoconjunctivitis is at least one selected from eyelid vernal keratoconjunctivitis, limbal vernal keratoconjunctivitis, and mixed vernal keratoconjunctivitis. In some embodiments, giant papillary conjunctivitis is caused by or partially by repetitive mechanical irritation of the conjunctiva. In some embodiments, repetitive mechanical irritation of the conjunctiva is associated with at least one selected from contact lens wear, use of ocular prostheses, use of conjunctival sutures, use of prominent scleral buckles, and corneal scarring. In some embodiments, atopic keratoconjunctivitis is accompanied by atopic dermatitis and / or asthma. In some embodiments, vesicular keratoconjunctivitis is caused by or partially by delayed hypersensitivity or inflammatory reactions of the cornea and conjunctiva to antigens expressed by various pathogens. In some embodiments, the pathogen is at least one selected from bacteria (e.g., Staphylococcus aureus, Streptococcus viridans, Mycobacterium tuberculosis), viruses (e.g., herpes simplex virus), chlamydia, fungi (e.g., Candida albicans), and parasites (e.g., tapeworms such as Hymenolepis microsporum; and nematodes). In some embodiments, the subject does not suffer from any ocular disease selected from viral conjunctivitis, bacterial conjunctivitis, chemical conjunctivitis, and dry eye syndrome or dry eye-related conditions. In some embodiments, the subject experiences at least one symptom prior to administration of the artificial polypeptide of formula (I), the symptom being selected from conjunctival redness, conjunctival edema, conjunctival hyperemia, eyelid redness, eyelid edema, eyelid hyperemia, itchy eye, visible corneal damage, mucus secretion, watery secretion, tearing, photophobia, foreign body sensation, and difficulty opening the eyes.In some embodiments, after administration of at least one dose of the artificial polypeptide of formula (I), the subject shows a reduction in at least one symptom selected from conjunctival redness, conjunctival edema, conjunctival hyperemia, eyelid redness, eyelid edema, eyelid hyperemia, itchy eyes, visible corneal damage, mucus secretion, watery secretion, tearing, photophobia, foreign body sensation, and difficulty opening the eyes. In some embodiments, after administration of at least one dose of the artificial polypeptide of formula (I), the subject shows improvement in at least one tissue selected from the conjunctiva, cornea, anterior chamber, iris, pupil, vitreous body, and fundus.

[0014] In another aspect, a method is provided for treating or preventing allergic conjunctivitis in a subject in need, comprising administering to the subject an effective amount of an artificial polypeptide of formula (II): X-Y(II), wherein X is a portion comprising a sequence having at least 80% identity with SEQ ID NO: 1, and Y is a portion comprising 10 to 50 amino acids, at least 50% of which are selected from I, V, L, F, C, M, and A; wherein Y comprises a sequence having at most 90% identity with SEQ ID NO: 2.

[0015] In some embodiments, X comprises a sequence having at least 90% identity with SEQ ID NO: 1, X comprises a sequence having at least 95% identity with SEQ ID NO: 1, or X comprises the sequence of SEQ ID NO: 1. In some embodiments, X comprises a sequence having at least 90% identity with SEQ ID NO: 1. In some embodiments, X comprises a sequence having at least 95% identity with SEQ ID NO: 1. In some embodiments, X comprises the sequence of SEQ ID NO: 1. In some embodiments, at least 50% of the amino acids in X are selected from R, K, N, D, Q, E, and H.

[0016] In some embodiments, Y contains a sequence having up to 80% identity with SEQ ID NO: 2, Y contains a sequence having up to 70% identity with SEQ ID NO: 2, or Y contains a sequence having up to 50% identity with SEQ ID NO: 2. In some embodiments, Y contains a sequence having up to 80% identity with SEQ ID NO: 2. In some embodiments, Y contains a sequence having up to 70% identity with SEQ ID NO: 2. In some embodiments, Y contains a sequence having up to 50% identity with SEQ ID NO: 2. In some embodiments, the total number of hydrophobic amino acids in Y is greater than 8, the total number of hydrophobic amino acids in Y is greater than 12, the total number of hydrophobic amino acids in Y is greater than 15, and / or the total number of hydrophilic amino acids in Y is no more than 5. In some embodiments, the total number of hydrophobic amino acids in Y is greater than 8. In some implementations, the total number of hydrophobic amino acids in Y is greater than 12.In some embodiments, the total number of hydrophobic amino acids in Y is greater than 15. In some embodiments, as described on page 3 / 68 of CN 121079312 A, the total number of hydrophilic amino acids in Y is no more than 5. In some embodiments, Y contains a sequence having at least 90% identity with any of SEQ ID NO: 16-18, or Y contains a sequence having at least 95% identity with any of SEQ ID NO: 16-18. In some embodiments, Y contains a sequence having at least 90% identity with any of SEQ ID NO: 16-18. In some embodiments, Y contains a sequence having at least 95% identity with any of SEQ ID NO: 16-18.

[0017] In some embodiments, the polypeptide contains a sequence having at least 90% identity with any of SEQ ID NO: 42-44.

[0018] In some embodiments, allergic conjunctivitis is at least one selected from seasonal allergic conjunctivitis, perennial allergic conjunctivitis, vernal keratoconjunctivitis, giant papillary conjunctivitis, atopic keratoconjunctivitis, and herpetic keratoconjunctivitis. In some embodiments, seasonal allergic conjunctivitis is caused by or partially by a seasonal allergen. In some embodiments, the seasonal allergen is at least one selected from tree pollen, weed pollen, grass pollen, and mold spores. In some embodiments, perennial allergic conjunctivitis is caused by or partially by a perennial allergen. In some embodiments, the perennial allergen is at least one selected from dust mites, cockroaches, and animal dander. In some embodiments, vernal keratoconjunctivitis is at least one selected from palpebral vernal keratoconjunctivitis, limbal vernal keratoconjunctivitis, and mixed vernal keratoconjunctivitis. In some embodiments, giant papillary conjunctivitis is caused by or partially by repeated mechanical irritation of the conjunctiva. In some embodiments, recurrent mechanical irritation of the conjunctiva is associated with at least one of the following: contact lens wear, use of ocular prostheses, use of conjunctival sutures, use of prominent scleral buckles, and corneal scarring. In some embodiments, atopic keratoconjunctivitis is accompanied by atopic dermatitis and / or asthma. In some embodiments, herpetic keratoconjunctivitis is caused by or in part by delayed hypersensitivity or inflammatory reactions of the cornea and conjunctiva to antigens expressed by various pathogens. In some embodiments, the pathogen is at least one of the following: bacteria (e.g., Staphylococcus aureus, Streptococcus viridans, Mycobacterium tuberculosis), viruses (e.g., herpes simplex virus), chlamydia, fungi (e.g., Candida albicans), and parasites (e.g., tapeworms such as Hymenolepis microsporum; and nematodes).In some embodiments, the subject does not suffer from any eye disease selected from viral conjunctivitis, bacterial conjunctivitis, chemical conjunctivitis, and dry eye syndrome or dry eye-related conditions. In some embodiments, the subject experiences at least one symptom selected from conjunctival redness, conjunctival edema, conjunctival hyperemia, eyelid redness, eyelid edema, eyelid hyperemia, itchy eye, visible corneal damage, mucus secretion, watery secretion, tearing, photophobia, foreign body sensation, and difficulty opening the eyes before administration of at least one dose of the artificial polypeptide of formula (II). In some embodiments, the subject shows a reduction in at least one symptom selected from conjunctival redness, conjunctival edema, conjunctival hyperemia, eyelid redness, eyelid edema, eyelid hyperemia, itchy eye, visible corneal damage, mucus secretion, watery secretion, tearing, photophobia, foreign body sensation, and difficulty opening the eyes after administration of at least one dose of the artificial polypeptide of formula (II). In some embodiments, the subject shows improvement in at least one tissue selected from the conjunctiva, cornea, anterior chamber, iris, pupil, vitreous body, and fundus after administration of at least one dose of the artificial polypeptide of formula (II).

[0019] In another aspect, a method for treating or preventing allergic conjunctivitis in a subject in need is provided, comprising administering to the subject an effective amount of the artificial polypeptide of formula (III): X-Y(III), wherein X is a portion comprising 40 to 65 amino acids, at least 50% of which are selected from H, R, K, D, Q, N, and E; and Y is a portion comprising a sequence having at least 80% identity with SEQ ID NO: 2, wherein the total number of H, R, K, D, Q, N, and E in X is less than 33.

[0020] In some embodiments, Y comprises a sequence having at least 90% identity with SEQ ID NO: 2, Y comprises a sequence having at least 95% identity with SEQ ID NO: 2 of document 4 / 68, page 25, CN 121079312 A, or Y comprises the sequence of SEQ ID NO: 2. In some embodiments, Y comprises a sequence having at least 90% identity with SEQ ID NO: 2. In some embodiments, Y comprises a sequence having at least 95% identity with SEQ ID NO: 2. In some embodiments, Y comprises the sequence of SEQ ID NO: 2. In some embodiments, at least 50% of the amino acids in Y are selected from I, V, L, F, C, M, and A.

[0021] In some embodiments, the total number of H, R, K, D, Q, N, and E in X is less than 30, the total number of H, R, K, D, Q, N, and E in X is less than 25, or the total number of H, R, K, D, Q, N, and E in X is less than 20. In some implementations, the total number of H, R, K, D, Q, N, and E in X is less than 30. In some implementations, the total number of H, R, K, D, Q, N, and E in X is less than 25.In some embodiments, the total number of H, R, K, D, Q, N, and E in X is less than 20. In some embodiments, the total number of hydrophilic amino acids in X is greater than 10; the total number of hydrophilic amino acids in X is greater than 15; the total number of hydrophilic amino acids in X is greater than 20; the total number of hydrophilic amino acids in X is greater than 25; the total number of hydrophobic amino acids in X is no more than 15; and / or the total number of hydrophobic amino acids in X is no more than 10. In some embodiments, the total number of hydrophilic amino acids in X is greater than 10. In some embodiments, the total number of hydrophilic amino acids in X is greater than 15. In some embodiments, the total number of hydrophilic amino acids in X is greater than 20. In some embodiments, the total number of hydrophilic amino acids in X is greater than 25. In some embodiments, the total number of hydrophobic amino acids in X is no more than 15. In some embodiments, the total number of hydrophobic amino acids in X is no more than 10. In some embodiments, X comprises a sequence having at least 90% identity with any of SEQ ID NO: 23-27, or X comprises a sequence having at least 95% identity with any of SEQ ID NO: 23-27. In some embodiments, X comprises a sequence having at least 90% identity with any of SEQ ID NO: 23-27. In some embodiments, X comprises a sequence having at least 95% identity with any of SEQ ID NO: 23-27.

[0022] In some embodiments, the polypeptide comprises a sequence having at least 90% identity with SEQ ID NO: 49-53.

[0023] In some embodiments, allergic conjunctivitis is at least one selected from seasonal allergic conjunctivitis, perennial allergic conjunctivitis, vernal keratoconjunctivitis, giant papillary conjunctivitis, atopic keratoconjunctivitis, and herpetic keratoconjunctivitis. In some embodiments, seasonal allergic conjunctivitis is caused by or partially by seasonal allergens. In some embodiments, the seasonal allergen is at least one selected from tree pollen, weed pollen, grass pollen, and mold spores. In some embodiments, perennial allergic conjunctivitis is caused by or partially by a perennial allergen. In some embodiments, the perennial allergen is at least one selected from dust mites, cockroaches, and animal dander. In some embodiments, vernal keratoconjunctivitis is at least one selected from eyelid vernal keratoconjunctivitis, limbal vernal keratoconjunctivitis, and mixed vernal keratoconjunctivitis. In some embodiments, giant papillary conjunctivitis is caused by or partially by repetitive mechanical irritation of the conjunctiva. In some embodiments, repetitive mechanical irritation of the conjunctiva is associated with at least one selected from contact lens wear, use of ocular prostheses, use of conjunctival sutures, use of prominent scleral buckles, and corneal scarring. In some embodiments, atopic keratoconjunctivitis is accompanied by atopic dermatitis and / or asthma.In some embodiments, herpetic keratoconjunctivitis is caused, or is partially caused, by a delayed-type hypersensitivity or inflammatory response of the cornea and conjunctiva to antigens expressed by various pathogens. In some embodiments, the pathogen is at least one selected from bacteria (e.g., Staphylococcus aureus, Streptococcus viridans, Mycobacterium tuberculosis), viruses (e.g., herpes simplex virus), chlamydia, fungi (e.g., Candida albicans), and parasites (e.g., tapeworms such as Hymenolepis microsporum; and nematodes). In some embodiments, the subject does not suffer from any ocular disease selected from viral conjunctivitis, bacterial conjunctivitis, chemical conjunctivitis, and dry eye syndrome or dry eye-related conditions. In some embodiments, the subject experiences at least one symptom prior to administration of the formula (III) artificial polypeptide, the symptom being selected from conjunctival redness, conjunctival edema, conjunctival hyperemia, eyelid redness, eyelid edema, eyelid hyperemia, itchy eye, visible corneal damage, mucus secretion, watery secretion, tearing, photophobia, foreign body sensation, and difficulty opening the eyes. In some embodiments, after administration of at least one dose of the artificial polypeptide of formula (III), the subject shows a reduction in at least one symptom selected from conjunctival redness, conjunctival edema, conjunctival hyperemia, eyelid redness, eyelid edema, eyelid hyperemia, itchy eyes, visible corneal damage, mucus secretion, watery secretion, tearing, photophobia, foreign body sensation, and difficulty opening the eyes. In some embodiments, after administration of at least one dose of the artificial polypeptide of formula (III), the subject shows improvement in at least one tissue selected from the conjunctiva, cornea, anterior chamber, iris, pupil, vitreous body, and fundus.

[0024] In another aspect, a method for treating or preventing allergic conjunctivitis in a subject in need is provided, comprising administering to the subject an effective amount of an artificial polypeptide of formula (IV): X-Y (IV), wherein X is a portion comprising 40 to 65 amino acids, at least 50% of which are selected from H, R, K, D, Q, N, and E; and Y is a portion comprising a sequence having at least 80% identity with SEQ ID NO: 2, wherein X comprises a sequence having at most 90% identity with SEQ ID NO: 1.

[0025] In some embodiments, X comprises a sequence having at most 80% identity with SEQ ID NO: 1, X comprises a sequence having at most 70% identity with SEQ ID NO: 1, or X comprises a sequence having at most 50% identity with SEQ ID NO: 1. In some embodiments, X comprises a sequence having at most 80% identity with SEQ ID NO: 1. In some embodiments, X comprises a sequence having at most 70% identity with SEQ ID NO: 1. In some implementations, X comprises a sequence that has up to 50% identity with SEQ ID NO: 1.In some embodiments, the total number of hydrophilic amino acids in X is greater than 10, greater than 15, greater than 20, greater than 25, and the total number of hydrophobic amino acids in X is no more than 15, and / or no more than 10. In some embodiments, the total number of hydrophilic amino acids in X is greater than 10. In some embodiments, the total number of hydrophilic amino acids in X is greater than 15. In some embodiments, the total number of hydrophilic amino acids in X is greater than 20. In some embodiments, the total number of hydrophilic amino acids in X is greater than 25. In some embodiments, the total number of hydrophobic amino acids in X is no more than 15. In some embodiments, the total number of hydrophobic amino acids in X is no more than 10. In some embodiments, X contains a sequence having at least 90% identity with any one of SEQ ID NO: 19-22 and 76-79, or X contains a sequence having at least 95% identity with any one of SEQ ID NO: 19-22 and 76-79. In some embodiments, X comprises a sequence having at least 90% identity with any one of SEQ ID NO: 19-22 and 76-79. In some embodiments, X comprises a sequence having at least 95% identity with any one of SEQ ID NO: 19-22 and 76-79.

[0026] In some embodiments, Y comprises a sequence having at least 90% identity with SEQ ID NO: 2, Y comprises a sequence having at least 95% identity with SEQ ID NO: 2, or Y comprises the sequence of SEQ ID NO: 2. In some embodiments, Y comprises a sequence having at least 90% identity with SEQ ID NO: 2. In some embodiments, Y comprises a sequence having at least 95% identity with SEQ ID NO: 2. In some embodiments, Y comprises the sequence of SEQ ID NO: 2. In some embodiments, at least 50% of the amino acids in Y are selected from I, V, L, F, C, M, and A.

[0027] In some embodiments, the polypeptide comprises a sequence having at least 90% identity with any one of SEQ ID NO: 45-48 and 86-89.

[0028] In some embodiments, allergic conjunctivitis is at least one selected from seasonal allergic conjunctivitis, perennial allergic conjunctivitis, vernal keratoconjunctivitis, giant papillary conjunctivitis, atopic keratoconjunctivitis, and herpetic keratoconjunctivitis. In some embodiments, seasonal allergic conjunctivitis is caused by or partially by a seasonal allergen. In some embodiments, the seasonal allergen is at least one selected from tree pollen, weed pollen, grass pollen, and mold spores.In some embodiments, perennial allergic conjunctivitis is caused by or partially by a perennial allergen. In some embodiments, the perennial allergen is at least one selected from dust mites, cockroaches, and animal dander. In some embodiments, vernal keratoconjunctivitis is at least one selected from eyelid vernal keratoconjunctivitis, limbal vernal keratoconjunctivitis, and mixed vernal keratoconjunctivitis. In some embodiments, giant papillary conjunctivitis is caused by or partially by repetitive mechanical irritation of the conjunctiva. In some embodiments, repetitive mechanical irritation of the conjunctiva is associated with at least one selected from contact lens wear, use of ocular prostheses, use of conjunctival sutures, use of prominent scleral buckles, and corneal scarring. In some embodiments, atopic keratoconjunctivitis is accompanied by atopic dermatitis and / or asthma. In some embodiments, vesicular keratoconjunctivitis is caused by or partially by delayed hypersensitivity or inflammatory reactions of the cornea and conjunctiva to antigens expressed by various pathogens. In some embodiments, the pathogen is at least one selected from bacteria (e.g., Staphylococcus aureus, Streptococcus viridans, Mycobacterium tuberculosis), viruses (e.g., herpes simplex virus), chlamydia, fungi (e.g., Candida albicans), and parasites (e.g., tapeworms such as Hymenolepis microsporum; and nematodes). In some embodiments, the subject does not suffer from any ocular disease selected from viral conjunctivitis, bacterial conjunctivitis, chemical conjunctivitis, and dry eye syndrome or dry eye-related conditions. In some embodiments, the subject experiences at least one symptom prior to administration of the formula (IV) artificial polypeptide, the symptom being selected from conjunctival redness, conjunctival edema, conjunctival hyperemia, eyelid redness, eyelid edema, eyelid hyperemia, itchy eye, visible corneal damage, mucus secretion, watery secretion, tearing, photophobia, foreign body sensation, and difficulty opening the eyes. In some embodiments, after administration of at least one dose of the artificial polypeptide of formula (IV), the subject shows relief of at least one symptom selected from conjunctival redness, conjunctival edema, conjunctival hyperemia, eyelid redness, eyelid edema, eyelid hyperemia, itchy eyes, visible corneal damage, mucus secretion, watery secretion, tearing, photophobia, foreign body sensation, and difficulty opening the eyes. In some embodiments, after administration of at least one dose of the artificial polypeptide of formula (IV), the subject shows improvement in at least one tissue selected from the conjunctiva, cornea, anterior chamber, iris, pupil, vitreous body, and fundus.

[0029] In another aspect, a method for treating or preventing allergic conjunctivitis in a subject in need is provided, comprising administering to the subject an effective amount of the artificial polypeptide of formula (V): X-Y (V), wherein X is a portion comprising a sequence having at least 80% identity with SEQ ID NO: 1, and Y is a portion comprising 10 to 30 amino acids, wherein Y comprises a sequence having at least 10 consecutive AAs of SEQ ID NO: 2.

[0030] In some embodiments, X comprises a sequence having at least 90% identity with SEQ ID NO: 1, X comprises a sequence having at least 95% identity with SEQ ID NO: 1, or X comprises the sequence of SEQ ID NO: 1. In some embodiments, X comprises a sequence having at least 90% identity with SEQ ID NO: 1. In some embodiments, X comprises a sequence having at least 95% identity with SEQ ID NO: 1. In some embodiments, X comprises the sequence of SEQ ID NO: 1. In some embodiments, at least 50% of the amino acids in X are selected from R, K, N, D, Q, E, and H. In some embodiments, X comprises a sequence having at least 80% identity with SEQ ID NO: 96, X comprises a sequence having at least 90% identity with SEQ ID NO: 96, X comprises a sequence having at least 95% identity with SEQ ID NO: 96, or X comprises the sequence of SEQ ID NO: 96. In some embodiments, X comprises a sequence having at least 80% identity with SEQ ID NO: 96. In some embodiments, X comprises a sequence having at least 90% identity with SEQ ID NO: 96. In some embodiments, X comprises a sequence having at least 95% identity with SEQ ID NO: 96. In some embodiments, X comprises the sequence of SEQ ID NO: 96.

[0031] In some embodiments, Y comprises 10 to 25 amino acids, Y comprises 10 to 20 amino acids, or Y comprises 10 to 15 amino acids. In some embodiments, Y comprises 10 to 25 amino acids. In some embodiments, Y comprises 10 to 20 amino acids. In some embodiments, Y comprises 10 to 15 amino acids.

[0032] In some embodiments, Y comprises a sequence having at most 80% identity with SEQ ID NO: 2, Y comprises a sequence having at most 70% identity with SEQ ID NO: 2, or Y comprises a sequence having at most 50% identity with SEQ ID NO: 2. (Specification page 7 / 68, 28 CN 121079312 A) In some embodiments, Y comprises a sequence having up to 80% identity with SEQ ID NO: 2. In some embodiments, Y comprises a sequence having up to 70% identity with SEQ ID NO: 2. In some embodiments, Y comprises a sequence having up to 50% identity with SEQ ID NO: 2.In some embodiments, Y comprises a sequence having at least 80% identity with any of SEQ ID NO: 97-103; Y comprises a sequence having at least 90% identity with any of SEQ ID NO: 97-103; Y comprises a sequence having at least 95% identity with any of SEQ ID NO: 97-103; or Y comprises any of SEQ ID NO: 97-103. In some embodiments, Y comprises a sequence having at least 80% identity with any of SEQ ID NO: 97-103. In some embodiments, Y comprises a sequence having at least 90% identity with any of SEQ ID NO: 97-103. In some embodiments, Y comprises a sequence having at least 95% identity with any of SEQ ID NO: 97-103. In some embodiments, Y comprises any of SEQ ID NO: 97-103.

[0033] In some embodiments, the polypeptide comprises a sequence having at least 90% identity with any one of SEQ ID NO: 53-56 and 104-110.

[0034] In some embodiments, allergic conjunctivitis is selected from at least one of seasonal allergic conjunctivitis, perennial allergic conjunctivitis, vernal keratoconjunctivitis, giant papillary conjunctivitis, atopic keratoconjunctivitis, and herpetic keratoconjunctivitis. In some embodiments, seasonal allergic conjunctivitis is caused by or partially by a seasonal allergen. In some embodiments, the seasonal allergen is selected from at least one of tree pollen, weed pollen, grass pollen, and mold spores. In some embodiments, perennial allergic conjunctivitis is caused by or partially by a perennial allergen. In some embodiments, the perennial allergen is selected from at least one of dust mites, cockroaches, and animal dander. In some embodiments, vernal keratoconjunctivitis is at least one selected from eyelid vernal keratoconjunctivitis, limbal vernal keratoconjunctivitis, and mixed vernal keratoconjunctivitis. In some embodiments, giant papillary conjunctivitis is caused by or in part by repetitive mechanical irritation of the conjunctiva. In some embodiments, repetitive mechanical irritation of the conjunctiva is associated with at least one selected from contact lens wear, use of ocular prostheses, use of conjunctival sutures, use of prominent scleral buckles, and corneal scarring. In some embodiments, atopic keratoconjunctivitis is accompanied by atopic dermatitis and / or asthma. In some embodiments, vesicular keratoconjunctivitis is caused by or in part by delayed hypersensitivity or inflammatory reactions of the cornea and conjunctiva to antigens expressed by various pathogens.In some embodiments, the pathogen is at least one selected from bacteria (e.g., Staphylococcus aureus, Streptococcus viridans, Mycobacterium tuberculosis), viruses (e.g., herpes simplex virus), chlamydia, fungi (e.g., Candida albicans), and parasites (e.g., tapeworms such as Hymenolepis microsporum; and nematodes). In some embodiments, the subject does not suffer from any ocular disease selected from viral conjunctivitis, bacterial conjunctivitis, chemical conjunctivitis, and dry eye syndrome or dry eye-related conditions. In some embodiments, the subject experiences at least one symptom prior to administration of the formula (V) artificial polypeptide, the symptom being selected from conjunctival redness, conjunctival edema, conjunctival hyperemia, eyelid redness, eyelid edema, eyelid hyperemia, itchy eye, visible corneal damage, mucus secretion, watery secretion, tearing, photophobia, foreign body sensation, and difficulty opening the eyes. In some embodiments, after administration of at least one dose of the artificial polypeptide of formula (V), the subject shows a reduction in at least one symptom selected from conjunctival redness, conjunctival edema, conjunctival hyperemia, eyelid redness, eyelid edema, eyelid hyperemia, itchy eyes, visible corneal damage, mucus secretion, watery secretion, tearing, photophobia, foreign body sensation, and difficulty opening the eyes. In some embodiments, after administration of at least one dose of the artificial polypeptide of formula (V), the subject shows improvement in at least one tissue selected from the conjunctiva, cornea, anterior chamber, iris, pupil, vitreous body, and fundus.

[0035] In another aspect, a method is provided for treating or preventing allergic conjunctivitis in a subject in need, comprising administering to the subject an effective amount of an artificial polypeptide of formula (VI): X-Y (VI), specification 8 / 68 pages 29 CN 121079312 A, wherein X is a portion comprising a mutant of the sequence SEQ ID NO: 1, characterized in that the mutant mutates at least 1, 2, 3, 4, 5, 6, 7, 8 or 9 Ds in SEQ ID NO: 1 to S, and / or mutates at least 1, 2, 3, 4, 5 or 6 Es in SEQ ID NO: 1 to T; and Y is a portion comprising a mutant of the sequence SEQ ID NO: 2, characterized in that the mutant mutates at least 1, 2, 3, 4 or 5 Cs in SEQ ID NO: 2 to A.

[0036] In some embodiments, X comprises a sequence having at least 70% identity with SEQ ID NO: 1, and / or X comprises a sequence having at most 95% identity with SEQ ID NO: 1. In some embodiments, X comprises a sequence having at least 70% identity with SEQ ID NO: 1. In some embodiments, X comprises a sequence having up to 95% identity with SEQ ID NO: 1. In some embodiments, the total number of R, K, T, A, N, Q, D, E, S, and G in X is greater than 30, and / or the total number of W, Y, F, M, L, I, and V in X is no more than 20.In some embodiments, the total number of R, K, T, A, N, Q, D, E, S, and G in X is greater than 30. In some embodiments, the total number of W, Y, F, M, L, I, and V in X is no more than 20. In some embodiments, X contains a sequence having at least 80% identity with any of SEQ ID NO: 80-83, X contains any of SEQ ID NO: 80-83, or X is any of SEQ ID NO: 80-83. In some embodiments, X contains a sequence having at least 80% identity with any of SEQ ID NO: 80-83. In some embodiments, X contains any of SEQ ID NO: 80-83. In some embodiments, X is any of SEQ ID NO: 80-83.

[0037] In some embodiments, Y contains a sequence having at least 80% identity with SEQ ID NO: 2, and / or Y contains a sequence having at most 95% identity with SEQ ID NO: 2. In some embodiments, Y comprises a sequence having at least 80% identity with SEQ ID NO: 2. In some embodiments, Y comprises a sequence having up to 95% identity with SEQ ID NO: 2. In some embodiments, at least 50% of the amino acids in Y are selected from I, V, L, F, C, M, and A. In some embodiments, the total number of R, K, T, A, N, Q, D, E, S, and G in Y is greater than 10, and / or the total number of W, Y, F, M, L, I, and V in Y does not exceed 20. In some embodiments, the total number of R, K, T, A, N, Q, D, E, S, and G in Y is greater than 10. In some embodiments, the total number of W, Y, F, M, L, I, and V in Y does not exceed 20. In some embodiments, Y comprises a sequence having at least 80% identity with SEQ ID NO: 3, Y comprises the sequence of SEQ ID NO: 3, or Y is the sequence of SEQ ID NO: 3. In some embodiments, Y comprises a sequence having at least 80% identity with SEQ ID NO: 3. In some embodiments, Y comprises the sequence of SEQ ID NO: 3. In some embodiments, Y is the sequence of SEQ ID NO: 3.

[0038] In some embodiments, the artificial polypeptide comprises a sequence having at least 80% identity with any one of SEQ ID NO: 90-93, the artificial polypeptide comprises any one of SEQ ID NO: 90-93, or the artificial polypeptide is any one of SEQ ID NO: 90-93.In some embodiments, the artificial polypeptide comprises a sequence having at least 80% identity with any one of SEQ ID NO: 90-93. In some embodiments, the artificial polypeptide comprises a sequence selected from any one of SEQ ID NO: 90-93. In some embodiments, the artificial polypeptide is a sequence selected from any one of SEQ ID NO: 90-93.

[0039] In some embodiments, allergic conjunctivitis is at least one selected from seasonal allergic conjunctivitis, perennial allergic conjunctivitis, vernal keratoconjunctivitis, giant papillary conjunctivitis, atopic keratoconjunctivitis, and herpetic keratoconjunctivitis. In some embodiments, seasonal allergic conjunctivitis is caused by or partially by a seasonal allergen. In some embodiments, the seasonal allergen is at least one selected from tree pollen, weed pollen, grass pollen, and mold spores. In some embodiments, perennial allergic conjunctivitis is caused by or partially by a perennial allergen. In some embodiments, the perennial allergen is at least one selected from dust mites, cockroaches, and animal dander. In some embodiments, vernal keratoconjunctivitis is at least one selected from eyelid vernal keratoconjunctivitis, limbal vernal keratoconjunctivitis, and mixed vernal keratoconjunctivitis. In some embodiments, giant papillary conjunctivitis is caused by or in part by repetitive mechanical irritation of the conjunctiva. In some embodiments, repetitive mechanical irritation of the conjunctiva is associated with at least one selected from contact lens wear, use of ocular prostheses, use of conjunctival sutures, use of prominent scleral buckles, and corneal scarring. In some embodiments, atopic keratoconjunctivitis is accompanied by atopic dermatitis and / or asthma. In some embodiments, herpetic keratoconjunctivitis is caused by or in part by delayed hypersensitivity or inflammatory reactions of the cornea and conjunctiva to antigens expressed by various pathogens. In some embodiments, the pathogen is at least one selected from bacteria (e.g., Staphylococcus aureus, Streptococcus viridans, Mycobacterium tuberculosis), viruses (e.g., herpes simplex virus), chlamydia, fungi (e.g., Candida albicans), and parasites (e.g., tapeworms such as Hymenolepis microsporum; and nematodes). In some embodiments, the subject does not suffer from any ocular disease selected from viral conjunctivitis, bacterial conjunctivitis, chemical conjunctivitis, and dry eye syndrome or dry eye-related conditions. In some embodiments, the subject experiences at least one symptom prior to administration of the formula (VI) artificial polypeptide, the symptom being selected from conjunctival redness, conjunctival edema, conjunctival hyperemia, eyelid redness, eyelid edema, eyelid hyperemia, itchy eye, visible corneal damage, mucus secretion, watery secretion, tearing, photophobia, foreign body sensation, and difficulty opening the eyes.In some embodiments, after administration of at least one dose of the formula (VI) artificial polypeptide, the subject shows a reduction in at least one symptom selected from conjunctival redness, conjunctival edema, conjunctival hyperemia, eyelid redness, eyelid edema, eyelid hyperemia, itchy eyes, visible corneal damage, mucus secretion, watery secretion, tearing, photophobia, foreign body sensation, and difficulty opening the eyes. In some embodiments, after administration of at least one dose of the formula (VI) artificial polypeptide, the subject shows improvement in at least one tissue selected from the conjunctiva, cornea, anterior chamber, iris, pupil, vitreous body, and fundus.

[0040] In another aspect, a method for treating or preventing allergic conjunctivitis in a subject in need is provided, comprising administering to the subject an effective amount of an artificial polypeptide of formula (VII): X-Y (VII), wherein X is a portion comprising a mutant of the sequence SEQ ID NO: 1, characterized in that the mutant has an insertion of at least 1, 2, 3, 4 or 5 amino acids relative to SEQ ID NO: 1, and Y is a portion comprising 10 to 30 amino acids, wherein Y comprises a sequence having at least 15 consecutive AAs of SEQ ID NO: 2.

[0041] In some embodiments, the amino acid insertion is located at the N-terminus of X, and / or the inserted amino acid is M. In some embodiments, the amino acid insertion is located at the N-terminus of X. In some embodiments, the inserted amino acid is M.

[0042] In some embodiments, at least 50% of the amino acids in X are selected from R, K, N, D, Q, E and H, and / or up to 60% of the amino acids in X are selected from R, K, N, D, Q, E and H. In some embodiments, at least 50% of the amino acids in X are selected from R, K, N, D, Q, E, and H. In some embodiments, up to 60% of the amino acids in X are selected from R, K, N, D, Q, E, and H. In some embodiments, the total number of E or D in X is at least 8, and / or the total number of E or D in X is at most 15. In some embodiments, the total number of E or D in X is at least 8. In some embodiments, the total number of E or D in X is at most 15. In some embodiments, the total number of R, K, T, A, N, Q, D, E, S, and G in X is greater than 30, and / or the total number of W, Y, F, M, L, I, and V in X does not exceed 20. In some embodiments, the total number of R, K, T, A, N, Q, D, E, S, and G in X is greater than 30. In some embodiments, the total number of W, Y, F, M, L, I, and V in X does not exceed 20. In some embodiments, X comprises a sequence having at least 80% identity with SEQ ID NO: 96, X comprises the sequence of SEQ ID NO: 96, or X is the sequence of SEQ ID NO: 96. In some embodiments, X comprises a sequence having at least 80% identity with SEQ ID NO: 96.In some embodiments, X comprises the sequence of SEQ ID NO: 96. In some embodiments, X is the sequence of SEQ ID NO: 96.

[0043] In some embodiments, Y is a portion comprising a mutant of the sequence SEQ ID NO: 2, characterized in that the mutant has at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 amino acid truncations relative to SEQ ID NO: 2, and optionally, at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20 amino acid truncations are located at the C-terminus of Y. In some embodiments, Y is a portion comprising a mutant of the sequence SEQ ID NO: 2, characterized in that the mutant has a truncation of at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acids relative to SEQ ID NO: 2. In some embodiments, the truncation of at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acids is located at the C-terminus of Y. In some embodiments, Y comprises 15 to 25 amino acids, Y comprises 18 to 25 amino acids, or Y comprises 20 to 25 amino acids. In some embodiments, Y comprises 15 to 25 amino acids. In some embodiments, Y comprises 18 to 25 amino acids. In some embodiments, Y comprises 20 to 25 amino acids. In some embodiments, 40-65% of the amino acids in Y are selected from I, V, L, F, C, M, and A. In some embodiments, the total number of R, K, T, A, N, Q, D, E, S, and G in Y does not exceed 10, and / or the total number of W, Y, F, M, L, I, and V in Y does not exceed 15. In some embodiments, the total number of R, K, T, A, N, Q, D, E, S, and G in Y does not exceed 10. In some embodiments, the total number of W, Y, F, M, L, I, and V in Y does not exceed 15. In some embodiments, Y contains a sequence having at least 80% identity with any of SEQ ID NO: 97-103, or Y is any of SEQ ID NO: 97-103. In some embodiments, Y contains a sequence having at least 80% identity with any of SEQ ID NO: 97-103. In some implementations, Y comprises any one of the sequences selected from SEQ ID NO: 97-103.In some embodiments, Y is any one of the sequences selected from SEQ ID NO: 97-103.

[0044] In some embodiments, the artificial polypeptide comprises a sequence having at least 80% identity with any one of SEQ ID NO: 104-110, or the artificial polypeptide is any one of the sequences selected from SEQ ID NO: 104-110. In some embodiments, the artificial polypeptide comprises a sequence having at least 80% identity with any one of SEQ ID NO: 104-110. In some embodiments, the artificial polypeptide comprises any one of the sequences selected from SEQ ID NO: 104-110. In some embodiments, the artificial polypeptide is any one of the sequences selected from SEQ ID NO: 104-110.

[0045] In some embodiments, allergic conjunctivitis is at least one selected from seasonal allergic conjunctivitis, perennial allergic conjunctivitis, vernal keratoconjunctivitis, giant papillary conjunctivitis, atopic keratoconjunctivitis, and herpetic keratoconjunctivitis. In some embodiments, seasonal allergic conjunctivitis is caused by or partially by a seasonal allergen. In some embodiments, the seasonal allergen is at least one selected from tree pollen, weed pollen, grass pollen, and mold spores. In some embodiments, perennial allergic conjunctivitis is caused by or partially by a perennial allergen. In some embodiments, the perennial allergen is at least one selected from dust mites, cockroaches, and animal dander. In some embodiments, vernal keratoconjunctivitis is at least one selected from eyelid vernal keratoconjunctivitis, limbal vernal keratoconjunctivitis, and mixed vernal keratoconjunctivitis. In some embodiments, giant papillary conjunctivitis is caused by or partially by repeated mechanical irritation of the conjunctiva. In some embodiments, recurrent mechanical irritation of the conjunctiva is associated with at least one of the following: contact lens wear, use of ocular prostheses, use of conjunctival sutures, use of prominent scleral buckles, and corneal scarring. In some embodiments, atopic keratoconjunctivitis is accompanied by atopic dermatitis and / or asthma. In some embodiments, herpetic keratoconjunctivitis is caused by or in part by delayed hypersensitivity or inflammatory reactions of the cornea and conjunctiva to antigens expressed by various pathogens. In some embodiments, the pathogen is at least one of the following: bacteria (e.g., Staphylococcus aureus, Streptococcus viridans, Mycobacterium tuberculosis), viruses (e.g., herpes simplex virus), chlamydia, fungi (e.g., Candida albicans), and parasites (e.g., tapeworms such as Hymenolepis microsporum; and nematodes). In some embodiments, the subject does not suffer from any ocular disease selected from viral conjunctivitis, bacterial conjunctivitis, chemical conjunctivitis, and dry eye syndrome or dry eye-related conditions.In some embodiments, the subject experiences at least one symptom prior to administration of the artificial polypeptide of formula (VII), the symptoms of which are selected from conjunctival redness, conjunctival edema, conjunctival hyperemia, eyelid redness, eyelid edema, eyelid hyperemia, itchy eyes, visible corneal damage, mucus secretion, watery secretion, tearing, photophobia, foreign body sensation, and difficulty opening the eyes. In some embodiments, after administration of at least one dose of the artificial polypeptide of formula (VII), the subject shows a reduction in at least one symptom selected from conjunctival redness, conjunctival edema, conjunctival hyperemia, eyelid redness, eyelid edema, eyelid hyperemia, itchy eyes, visible corneal damage, mucus secretion, watery secretion, tearing, photophobia, foreign body sensation, and difficulty opening the eyes. In some embodiments, after administration of at least one dose of the artificial polypeptide of formula (VII), the subject shows improvement in at least one tissue selected from the conjunctiva, cornea, anterior chamber, iris, pupil, vitreous body, and fundus.

[0046] In another aspect, a method is provided for treating or preventing allergic conjunctivitis in a subject in need, comprising administering to the subject an effective amount of a mutant of an artificial polypeptide of formula (I), X-Y (I), wherein X is a portion comprising a sequence having at least 80% identity with SEQ ID NO: 1, Y is a portion comprising 10 to 50 amino acids, at least 50% of which are selected from I, V, L, F, C, M and A, and Y comprises a total number of less than 5 cysteines (C), characterized in that the mutant mutates at least 1, 2, 3, 4, 5, 6, 7, 8 or 9 Ds in X to S, and / or mutates at least 1, 2, 3, 4, 5 or 6 Es in X to T.

[0047] In some embodiments, at least 20% of the amino acids in X are selected from R, K, N, D, Q, E, and H; at least 30% of the amino acids in X are selected from R, K, N, D, Q, E, and H; at most 90% of the amino acids in X are selected from R, K, N, D, Q, E, and H; and / or at most 80% of the amino acids in X are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 20% of the amino acids in X are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 30% of the amino acids in X are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 90% of the amino acids in X are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 80% of the amino acids in X are selected from R, K, N, D, Q, E, and H. In some embodiments, X comprises a sequence having at least 70% identity with SEQ ID NO: 1.

[0048] In some embodiments, Y contains a total of less than 4 cysteine ​​(C) residues, or Y contains a total of less than 3 cysteine ​​(C) residues. In some embodiments, Y contains a total of less than 4 cysteine ​​(C) residues.In some embodiments, Y contains less than 3 cysteine ​​(C) residues. In some embodiments, Y contains more than 8, more than 12, more than 15, and / or less than 5 hydrophilic amino acids. In some embodiments, Y contains more than 8, more than 12, more than 15, and / or less than 5 hydrophilic amino acids. In some embodiments, Y contains more than 8, more than 12, more than 15, and less than 5 hydrophilic amino acids. In some embodiments, Y contains less than 5, more than 5, and more than 5, a sequence having at least 90% identity with any one of SEQ ID NO: 3-15, 58-61, and 84-85, or a sequence having at least 90% identity with any one of SEQ ID NO: 3-18, 58-61, and 84-85. In some embodiments, Y comprises a sequence having at least 90% identity with any one of SEQ ID NO: 3-15, 58-61, and 84-85. In some embodiments, Y comprises a sequence having at least 90% identity with any one of SEQ ID NO: 3-18, 58-61, and 84-85.

[0049] In some embodiments, allergic conjunctivitis is at least one selected from seasonal allergic conjunctivitis, perennial allergic conjunctivitis, vernal keratoconjunctivitis, giant papillary conjunctivitis, atopic keratoconjunctivitis, and herpetic keratoconjunctivitis. In some embodiments, seasonal allergic conjunctivitis is caused by or partially by a seasonal allergen. In some embodiments, the seasonal allergen is at least one selected from tree pollen, weed pollen, grass pollen, and mold spores. In some embodiments, perennial allergic conjunctivitis is caused by or partially by a perennial allergen. In some embodiments, the perennial allergen is at least one selected from dust mites, cockroaches, and animal dander. In some embodiments, vernal keratoconjunctivitis (CN 121079312 A, page 12 / 68) is at least one selected from eyelid vernal keratoconjunctivitis, limbal vernal keratoconjunctivitis, and mixed vernal keratoconjunctivitis. In some embodiments, giant papillary conjunctivitis is caused by or in part by repetitive mechanical irritation of the conjunctiva. In some embodiments, repetitive mechanical irritation of the conjunctiva is associated with at least one selected from contact lens wear, use of ocular prostheses, use of conjunctival sutures, use of prominent scleral buckles, and corneal scarring. In some embodiments, atopic keratoconjunctivitis is accompanied by atopic dermatitis and / or asthma. In some embodiments, vesicular keratoconjunctivitis is caused by or in part by delayed hypersensitivity or inflammatory reactions of the cornea and conjunctiva to antigens expressed by various pathogens.In some embodiments, the pathogen is at least one selected from bacteria (e.g., Staphylococcus aureus, Streptococcus viride, Mycobacterium tuberculosis), viruses (e.g., herpes simplex virus), chlamydia, fungi (e.g., Candida albicans), and parasites (e.g., tapeworms such as Hymenolepis microsporum; and nematodes). In some embodiments, the subject does not suffer from any ocular disease selected from viral conjunctivitis, bacterial conjunctivitis, chemical conjunctivitis, and dry eye syndrome or dry eye-related conditions. In some embodiments, the subject experiences at least one symptom prior to administration of the mutant of formula (I) artificial polypeptide, said symptom being selected from conjunctival redness, conjunctival edema, conjunctival hyperemia, eyelid redness, eyelid edema, eyelid hyperemia, itchy eyes, visible corneal damage, mucus secretion, watery secretion, tearing, photophobia, foreign body sensation, and difficulty opening the eyes. In some embodiments, after administration of at least one dose of a mutant of the artificial polypeptide of formula (I), the subject shows a reduction in at least one symptom selected from conjunctival redness, conjunctival edema, conjunctival hyperemia, eyelid redness, eyelid edema, eyelid hyperemia, itchy eyes, visible corneal damage, mucus secretion, watery secretion, tearing, photophobia, foreign body sensation, and difficulty opening the eyes. In some embodiments, after administration of at least one dose of a mutant of the artificial polypeptide of formula (I), the subject shows improvement in at least one tissue selected from the conjunctiva, cornea, anterior chamber, iris, pupil, vitreous body, and fundus.

[0050] In another aspect, a method is provided for treating or preventing allergic conjunctivitis in a subject in need, comprising administering to the subject an effective amount of a mutant of an artificial polypeptide of formula (II), X-Y (II), wherein X is a portion comprising a sequence having at least 80% identity with SEQ ID NO: 1, Y is a portion comprising 10 to 50 amino acids, at least 50% of which are selected from I, V, L, F, C, M and A, Y comprising a sequence having at most 90% identity with SEQ ID NO: 2, characterized in that the mutant mutates at least 1, 2, 3, 4, 5, 6, 7, 8 or 9 Ds in X to S, and / or mutates at least 1, 2, 3, 4, 5 or 6 Es in X to T.

[0051] In some embodiments, at least 20% of the amino acids in X are selected from R, K, N, D, Q, E, and H; at least 30% of the amino acids in X are selected from R, K, N, D, Q, E, and H; at most 90% of the amino acids in X are selected from R, K, N, D, Q, E, and H; and / or at most 80% of the amino acids in X are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 20% of the amino acids in X are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 30% of the amino acids in X are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 90% of the amino acids in X are selected from R, K, N, D, Q, E, and H.In some embodiments, up to 80% of the amino acids in X are selected from R, K, N, D, Q, E, and H. In some embodiments, X comprises a sequence having at least 70% identity with SEQ ID NO: 1.

[0052] In some embodiments, Y comprises a sequence having at most 80% identity with SEQ ID NO: 2, or Y comprises a sequence having at most 70% identity with SEQ ID NO: 2. In some embodiments, Y comprises a sequence having at most 80% identity with SEQ ID NO: 2. In some embodiments, Y comprises a sequence having at most 70% identity with SEQ ID NO: 2. In some embodiments, the total number of hydrophobic amino acids in Y is greater than 8, the total number of hydrophobic amino acids in Y is greater than 12, the total number of hydrophobic amino acids in Y is greater than 15, and / or the total number of hydrophilic amino acids in Y is not more than 5. In some embodiments, the total number of hydrophobic amino acids in Y is greater than 8. In some embodiments, the total number of hydrophobic amino acids in Y is greater than 12. In some embodiments, the total number of hydrophobic amino acids in Y is greater than 15. In some embodiments, the total number of hydrophilic amino acids in Y does not exceed 5. In some embodiments, Y contains a sequence having at least 90% identity with any of SEQ ID NO: 16-18, or Y contains a sequence having at least 95% identity with any of SEQ ID NO: 16-18. In some embodiments, Y contains a sequence having at least 90% identity with any of SEQ ID NO: 16-18. In some embodiments, Y contains a sequence having at least 95% identity with any of SEQ ID NO: 16-18.

[0053] In some embodiments, allergic conjunctivitis is at least one selected from seasonal allergic conjunctivitis, perennial allergic conjunctivitis, vernal keratoconjunctivitis, giant papillary conjunctivitis, atopic keratoconjunctivitis, and herpetic keratoconjunctivitis. In some embodiments, seasonal allergic conjunctivitis is caused by or partially by seasonal allergens. In some embodiments, the seasonal allergen is at least one selected from tree pollen, weed pollen, grass pollen, and mold spores. In some embodiments, perennial allergic conjunctivitis is caused by or partially by a perennial allergen. In some embodiments, the perennial allergen is at least one selected from dust mites, cockroaches, and animal dander. In some embodiments, vernal keratoconjunctivitis is at least one selected from palpebral vernal keratoconjunctivitis, limbal vernal keratoconjunctivitis, and mixed vernal keratoconjunctivitis. In some embodiments, giant papillary conjunctivitis is caused by or partially by repetitive mechanical irritation of the conjunctiva.In some embodiments, recurrent mechanical irritation of the conjunctiva is associated with at least one of the following: contact lens wear, use of ocular prostheses, use of conjunctival sutures, use of prominent scleral buckles, and corneal scarring. In some embodiments, atopic keratoconjunctivitis is accompanied by atopic dermatitis and / or asthma. In some embodiments, herpetic keratoconjunctivitis is caused by or in part by delayed hypersensitivity or inflammatory reactions of the cornea and conjunctiva to antigens expressed by various pathogens. In some embodiments, the pathogen is at least one of the following: bacteria (e.g., Staphylococcus aureus, Streptococcus viridans, Mycobacterium tuberculosis), viruses (e.g., herpes simplex virus), chlamydia, fungi (e.g., Candida albicans), and parasites (e.g., tapeworms such as Hymenolepis microsporum; and nematodes). In some embodiments, the subject does not suffer from any ocular disease selected from viral conjunctivitis, bacterial conjunctivitis, chemical conjunctivitis, and dry eye syndrome or dry eye-related conditions. In some embodiments, the subject experiences at least one symptom prior to administration of a mutant of the formula (II) artificial polypeptide, the symptom being selected from conjunctival redness, conjunctival edema, conjunctival hyperemia, eyelid redness, eyelid edema, eyelid hyperemia, itchy eyes, visible corneal damage, mucus secretion, watery secretion, tearing, photophobia, foreign body sensation, and difficulty opening the eyes. In some embodiments, after administration of at least one dose of the mutant of the formula (II) artificial polypeptide, the subject shows a reduction in at least one symptom, the symptom being selected from conjunctival redness, conjunctival edema, conjunctival hyperemia, eyelid redness, eyelid edema, eyelid hyperemia, itchy eyes, visible corneal damage, mucus secretion, watery secretion, tearing, photophobia, foreign body sensation, and difficulty opening the eyes. In some embodiments, after administration of at least one dose of the mutant of the formula (II) artificial polypeptide, the subject shows improvement in at least one tissue selected from the conjunctiva, cornea, anterior chamber, iris, pupil, vitreous body, and fundus.

[0054] In another aspect, a method is provided for treating or preventing allergic conjunctivitis in a subject in need, comprising administering to the subject an effective amount of a mutant of an artificial polypeptide of formula (III), X-Y (III), wherein X is a portion comprising 40 to 65 amino acids, at least 50% of which are selected from H, R, K, D, Q, N and E, Y is a portion comprising a sequence having at least 80% identity with SEQ ID NO: 2, and the total number of H, R, K, D, Q, N and E in X is less than 33, characterized in that the mutant mutates at least 1, 2, 3, 4, 5, 6, 7, 8 or 9 Ds in X to S, and / or mutates at least 1, 2, 3, 4, 5 or 6 Es in X to T.

[0055] In some embodiments, at least 20% of the amino acids in X are selected from R, K, N, D, Q, E, and H; at least 30% of the amino acids in X are selected from R, K, N, D, Q, E, and H; at most 90% of the amino acids in X are selected from R, K, N, D, Q, E, and H; and / or at most 80% of the amino acids in X are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 20% of the amino acids in X are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 30% of the amino acids in X are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 90% of the amino acids in X are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 80% of the amino acids in X are selected from R, K, N, D, Q, E, and H. In some embodiments, X comprises a sequence having at least 70% identity with SEQ ID NO: 1. In some embodiments, the total number of H, R, K, D, Q, N, and E in X is less than 30, the total number of H, R, K, D, Q, N, and E in X is less than 25, or the total number of H, R, K, D, Q, N, and E in X is less than 20. In some embodiments, the total number of H, R, K, D, Q, N, and E in X is less than 30. In some embodiments, the total number of H, R, K, D, Q, N, and E in X is less than 25. In some embodiments, the total number of H, R, K, D, Q, N, and E in X is less than 20. In some embodiments, the total number of hydrophilic amino acids in X is greater than 10, the total number of hydrophilic amino acids in X is greater than 15, the total number of hydrophilic amino acids in X is greater than 20, the total number of hydrophilic amino acids in X is greater than 25, the total number of hydrophobic amino acids in X is no more than 15, and / or the total number of hydrophobic amino acids in X is no more than 10. In some embodiments, the total number of hydrophilic amino acids in X is greater than 10. In some embodiments, the total number of hydrophilic amino acids in X is greater than 15. In some embodiments, the total number of hydrophilic amino acids in X is greater than 20. In some embodiments, the total number of hydrophilic amino acids in X is greater than 25. In some embodiments, the total number of hydrophobic amino acids in X is no more than 15. In some embodiments, the total number of hydrophobic amino acids in X is no more than 10.

[0056] In some embodiments, Y comprises a sequence having at least 90% identity with SEQ ID NO: 2, or Y comprises the sequence of SEQ ID NO: 2. In some embodiments, Y comprises a sequence having at least 90% identity with SEQ ID NO: 2. In some embodiments, Y comprises the sequence of SEQ ID NO: 2. In some embodiments, at least 50% of the amino acids in Y are selected from I, V, L, F, C, M, and A.

[0057] In some embodiments, allergic conjunctivitis is at least one selected from seasonal allergic conjunctivitis, perennial allergic conjunctivitis, vernal keratoconjunctivitis, giant papillary conjunctivitis, atopic keratoconjunctivitis, and herpetic keratoconjunctivitis. In some embodiments, seasonal allergic conjunctivitis is caused by or partially by a seasonal allergen. In some embodiments, the seasonal allergen is at least one selected from tree pollen, weed pollen, grass pollen, and mold spores. In some embodiments, perennial allergic conjunctivitis is caused by or partially by a perennial allergen. In some embodiments, the perennial allergen is at least one selected from dust mites, cockroaches, and animal dander. In some embodiments, vernal keratoconjunctivitis is at least one selected from eyelid vernal keratoconjunctivitis, limbal vernal keratoconjunctivitis, and mixed vernal keratoconjunctivitis. In some embodiments, giant papillary conjunctivitis is caused by or partially by repeated mechanical irritation of the conjunctiva. In some embodiments, recurrent mechanical irritation of the conjunctiva is associated with at least one of the following: contact lens wear, use of ocular prostheses, use of conjunctival sutures, use of prominent scleral buckles, and corneal scarring. In some embodiments, atopic keratoconjunctivitis is accompanied by atopic dermatitis and / or asthma. In some embodiments, herpetic keratoconjunctivitis is caused by or in part by delayed hypersensitivity or inflammatory reactions of the cornea and conjunctiva to antigens expressed by various pathogens. In some embodiments, the pathogen is at least one of the following: bacteria (e.g., Staphylococcus aureus, Streptococcus viridans, Mycobacterium tuberculosis), viruses (e.g., herpes simplex virus), chlamydia, fungi (e.g., Candida albicans), and parasites (e.g., tapeworms such as Hymenolepis microsporum; and nematodes). In some embodiments, the subject does not suffer from any ocular disease selected from viral conjunctivitis, bacterial conjunctivitis, chemical conjunctivitis, and dry eye syndrome or dry eye-related conditions. In some embodiments, the subject experiences at least one symptom prior to administration of a mutant of the formula (III) artificial polypeptide, the symptom being selected from conjunctival redness, conjunctival edema, conjunctival hyperemia, eyelid redness, eyelid edema, eyelid hyperemia, itchy eyes, visible corneal damage, mucus secretion, watery secretion, tearing, photophobia, foreign body sensation, and difficulty opening the eyes. In some embodiments, after administration of at least one dose of the mutant of the formula (III) artificial polypeptide, the subject exhibits a reduction in at least one symptom, the symptom being selected from conjunctival redness, conjunctival edema, conjunctival hyperemia, eyelid redness, eyelid edema, eyelid hyperemia, itchy eyes, visible corneal damage, mucus secretion, watery secretion, tearing, photophobia, foreign body sensation, and difficulty opening the eyes.In some embodiments, the subject shows improvement in at least one tissue selected from the conjunctiva, cornea, anterior chamber, iris, pupil, vitreous body, and fundus after administration of at least one dose of a mutant of the formula (III) artificial polypeptide.

[0058] In another aspect, a method for treating or preventing allergic conjunctivitis in a subject in need is provided, comprising administering to the subject an effective amount of a mutant of the formula (IV) artificial polypeptide, X-Y (IV), wherein X is a portion comprising 40 to 65 amino acids, at least 50% of which are selected from H, R, K, D, Q, N, and E, Y is a portion comprising a sequence having at least 80% identity with SEQ ID NO: 2, and X comprises a sequence having at most 90% identity with SEQ ID NO: 1, characterized in that the mutant mutates at least 1, 2, 3, 4, 5, 6, 7, 8, or 9 Ds in X to S, and / or mutates at least 1, 2, 3, 4, 5, or 6 Es in X to T.

[0059] In some embodiments, at least 20% of the amino acids in X are selected from R, K, N, D, Q, E, and H; at least 30% of the amino acids in X are selected from R, K, N, D, Q, E, and H; at most 90% of the amino acids in X are selected from R, K, N, D, Q, E, and H; and / or at most 80% of the amino acids in X are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 20% of the amino acids in X are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 30% of the amino acids in X are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 90% of the amino acids in X are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 80% of the amino acids in X are selected from R, K, N, D, Q, E, and H. In some embodiments, X comprises a sequence having at least 70% identity with SEQ ID NO: 1. In some embodiments, the total number of hydrophilic amino acids in X is greater than 10, the total number of hydrophilic amino acids in X is greater than 15, the total number of hydrophilic amino acids in X is greater than 20, the total number of hydrophilic amino acids in X is greater than 25, the total number of hydrophobic amino acids in X is not more than 15, and / or the total number of hydrophobic amino acids in X is not more than 10. In some embodiments, the total number of hydrophilic amino acids in X is greater than 10. In some embodiments, the total number of hydrophilic amino acids in X is greater than 15. In some embodiments, the total number of hydrophilic amino acids in X is greater than 20. In some embodiments, the total number of hydrophilic amino acids in X is greater than 25. In some embodiments, the total number of hydrophobic amino acids in X is not more than 15. In some embodiments, the total number of hydrophobic amino acids in X is not more than 10.

[0060] In some embodiments, Y comprises a sequence having at least 90% identity with SEQ ID NO: 2, or Y comprises a sequence of SEQ ID NO: 2.In some embodiments, Y comprises a sequence having at least 90% identity with SEQ ID NO: 2. In some embodiments, Y comprises the sequence of SEQ ID NO: 2. In some embodiments, at least 50% of the amino acids in Y are selected from I, V, L, F, C, M, and A.

[0061] In some embodiments, allergic conjunctivitis is selected from at least one of seasonal allergic conjunctivitis, perennial allergic conjunctivitis, vernal keratoconjunctivitis, giant papillary conjunctivitis, atopic keratoconjunctivitis, and herpetic keratoconjunctivitis. In some embodiments, seasonal allergic conjunctivitis is caused by or partially by a seasonal allergen. In some embodiments, the seasonal allergen is selected from at least one of tree pollen, weed pollen, grass pollen, and mold spores. In some embodiments, perennial allergic conjunctivitis is caused by or partially by a perennial allergen. In some embodiments, the perennial allergen is selected from at least one of dust mites, cockroaches, and animal dander. In some embodiments, vernal keratoconjunctivitis is at least one selected from eyelid vernal keratoconjunctivitis, limbal vernal keratoconjunctivitis, and mixed vernal keratoconjunctivitis. In some embodiments, giant papillary conjunctivitis is caused by or in part by repetitive mechanical irritation of the conjunctiva. In some embodiments, repetitive mechanical irritation of the conjunctiva is associated with at least one selected from contact lens wear, use of ocular prostheses (page 16 / 68, 37 CN 121079312 A), use of conjunctival sutures, use of prominent scleral buckles, and corneal scarring. In some embodiments, atopic keratoconjunctivitis is accompanied by atopic dermatitis and / or asthma. In some embodiments, herpetic keratoconjunctivitis is caused by or in part by delayed hypersensitivity or inflammatory reactions of the cornea and conjunctiva to antigens expressed by various pathogens. In some embodiments, the pathogen is at least one selected from bacteria (e.g., Staphylococcus aureus, Streptococcus viride, Mycobacterium tuberculosis), viruses (e.g., herpes simplex virus), chlamydia, fungi (e.g., Candida albicans), and parasites (e.g., tapeworms such as Hymenolepis microsporum; and nematodes). In some embodiments, the subject does not suffer from any ocular disease selected from viral conjunctivitis, bacterial conjunctivitis, chemical conjunctivitis, and dry eye syndrome or dry eye-related conditions. In some embodiments, the subject experiences at least one symptom prior to administration of the mutant of formula (IV) artificial polypeptide, the symptom being selected from conjunctival redness, conjunctival edema, conjunctival hyperemia, eyelid redness, eyelid edema, eyelid hyperemia, itchy eyes, visible corneal damage, mucus secretion, watery secretion, tearing, photophobia, foreign body sensation, and difficulty opening the eyes.In some embodiments, subjects, after administration of at least one dose of a mutant of the formula (IV) artificial polypeptide, exhibit a reduction in at least one symptom selected from conjunctival redness, conjunctival edema, conjunctival hyperemia, eyelid redness, eyelid edema, eyelid hyperemia, itchy eyes, visible corneal damage, mucus secretion, watery secretion, tearing, photophobia, foreign body sensation, and difficulty opening the eyes. In some embodiments, subjects, after administration of at least one dose of a mutant of the formula (IV) artificial polypeptide, exhibit improvement in at least one tissue selected from the conjunctiva, cornea, anterior chamber, iris, pupil, vitreous body, and fundus.

[0062] In another aspect, a method is provided for treating or preventing allergic conjunctivitis in a subject in need, comprising administering to the subject an effective amount of a mutant of an artificial polypeptide of formula (V), X-Y (V), wherein X is a portion comprising a sequence having at least 80% identity with SEQ ID NO: 1, and Y is a portion comprising 10 to 30 amino acids, wherein Y comprises a sequence having at least 10 consecutive AAs of SEQ ID NO: 2, characterized in that the mutant mutates at least 1, 2, 3, 4, 5, 6, 7, 8 or 9 Ds in X to S, and / or mutates at least 1, 2, 3, 4, 5 or 6 Es in X to T.

[0063] In some embodiments, at least 20% of the amino acids in X are selected from R, K, N, D, Q, E, and H; at least 30% of the amino acids in X are selected from R, K, N, D, Q, E, and H; at most 90% of the amino acids in X are selected from R, K, N, D, Q, E, and H; and / or at most 80% of the amino acids in X are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 20% of the amino acids in X are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 30% of the amino acids in X are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 90% of the amino acids in X are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 80% of the amino acids in X are selected from R, K, N, D, Q, E, and H. In some embodiments, X comprises a sequence having at least 70% identity with SEQ ID NO: 1.

[0064] In some embodiments, Y comprises 10 to 25 amino acids, Y comprises 10 to 20 amino acids, or Y comprises 10 to 15 amino acids. In some embodiments, Y comprises 10 to 25 amino acids. In some embodiments, Y comprises 10 to 20 amino acids. In some embodiments, Y comprises 10 to 15 amino acids. In some embodiments, Y comprises a sequence having up to 80% identity with SEQ ID NO: 2, Y comprises a sequence having up to 70% identity with SEQ ID NO: 2, or Y comprises a sequence having up to 50% identity with SEQ ID NO: 2.In some embodiments, Y comprises a sequence having up to 80% identity with SEQ ID NO: 2. In some embodiments, Y comprises a sequence having up to 70% identity with SEQ ID NO: 2. In some embodiments, Y comprises a sequence having up to 50% identity with SEQ ID NO: 2.

[0065] In some embodiments, allergic conjunctivitis is at least one selected from seasonal allergic conjunctivitis, perennial allergic conjunctivitis, vernal keratoconjunctivitis, giant papillary conjunctivitis, atopic keratoconjunctivitis, and herpetic keratoconjunctivitis. In some embodiments, seasonal allergic conjunctivitis is caused by or partially by a seasonal allergen. In some embodiments, the seasonal allergen is at least one selected from tree pollen, weed pollen, grass pollen, and mold spores. In some embodiments, perennial allergic conjunctivitis is caused by or partially by a perennial allergen. In some embodiments, the perennial allergen is at least one selected from dust mites, cockroaches, and animal dander. In some embodiments, vernal keratoconjunctivitis is at least one selected from eyelid vernal keratoconjunctivitis, limbal vernal keratoconjunctivitis, and mixed vernal keratoconjunctivitis. In some embodiments, giant papillary conjunctivitis is caused by or in part by repetitive mechanical irritation of the conjunctiva. In some embodiments, repetitive mechanical irritation of the conjunctiva is associated with at least one selected from contact lens wear, use of ocular prostheses, use of conjunctival sutures, use of prominent scleral buckles, and corneal scarring. In some embodiments, atopic keratoconjunctivitis is accompanied by atopic dermatitis and / or asthma. In some embodiments, vesicular keratoconjunctivitis is caused by or in part by delayed hypersensitivity or inflammatory reactions of the cornea and conjunctiva to antigens expressed by various pathogens. In some embodiments, the pathogen is at least one selected from bacteria (e.g., Staphylococcus aureus, Streptococcus viride, Mycobacterium tuberculosis), viruses (e.g., herpes simplex virus), chlamydia, fungi (e.g., Candida albicans), and parasites (e.g., tapeworms such as Hymenolepis microsporum; and nematodes). In some embodiments, the subject does not suffer from any ocular disease selected from viral conjunctivitis, bacterial conjunctivitis, chemical conjunctivitis, and dry eye syndrome or dry eye-related conditions. In some embodiments, the subject experiences at least one symptom prior to administration of the mutant of formula (V) artificial polypeptide, the symptom being selected from conjunctival redness, conjunctival edema, conjunctival hyperemia, eyelid redness, eyelid edema, eyelid hyperemia, itchy eyes, visible corneal damage, mucus secretion, watery secretion, tearing, photophobia, foreign body sensation, and difficulty opening the eyes.In some embodiments, after administration of at least one dose of a mutant of the formula (V) artificial polypeptide, the subject shows a reduction in at least one symptom selected from conjunctival redness, conjunctival edema, conjunctival hyperemia, eyelid redness, eyelid edema, eyelid hyperemia, itchy eyes, visible corneal damage, mucus secretion, watery secretion, tearing, photophobia, foreign body sensation, and difficulty opening the eyes. In some embodiments, after administration of at least one dose of a mutant of the formula (V) artificial polypeptide, the subject shows improvement in at least one tissue selected from the conjunctiva, cornea, anterior chamber, iris, pupil, vitreous body, and fundus.

[0066] In another aspect, a method for treating or preventing allergic conjunctivitis in a subject in need is provided, comprising administering to the subject an effective amount of a polypeptide or a fragment or variant thereof, the polypeptide having at least 70% identity with any one of SEQ ID NO: 28, SEQ ID NO: 57, and 62-74.

[0067] In some embodiments, the polypeptide is a polypeptide of any one of SEQ ID NO: 28, SEQ ID NO: 57, and 62-74, or a fragment or variant thereof. In some embodiments, the polypeptide is a polypeptide of any one of SEQ ID NO: 28, SEQ ID NO: 57, and 62-74, or a polypeptide of SEQ ID NO: 28. In some embodiments, the polypeptide is a polypeptide of any one of SEQ ID NO: 28, SEQ ID NO: 57, and 62-74, or a fragment or variant thereof. In some embodiments, the polypeptide is a polypeptide of any one of SEQ ID NO: 28, SEQ ID NO: 57, and 62-74. In some embodiments, the polypeptide is a polypeptide of any one of SEQ ID NO: 28 and 62-74. In some embodiments, the polypeptide is a polypeptide of SEQ ID NO: 28.

[0068] In some embodiments, allergic conjunctivitis is at least one selected from seasonal allergic conjunctivitis, perennial allergic conjunctivitis, vernal keratoconjunctivitis, giant papillary conjunctivitis, atopic keratoconjunctivitis, and vesicular keratoconjunctivitis. In some embodiments, seasonal allergic conjunctivitis is caused by or partially by a seasonal allergen. In some embodiments, the seasonal allergen is at least one selected from tree pollen, weed pollen, grass pollen, and mold spores. In some embodiments, perennial allergic conjunctivitis is caused by or partially by a perennial allergen. In some embodiments, the perennial allergen is at least one selected from dust mites, cockroaches, and animal dander. In some embodiments, vernal keratoconjunctivitis is at least one selected from eyelid vernal keratoconjunctivitis, limbal vernal keratoconjunctivitis, and mixed vernal keratoconjunctivitis.In some embodiments, giant papillary conjunctivitis is caused by or in part by repetitive mechanical irritation of the conjunctiva. In some embodiments, repetitive mechanical irritation of the conjunctiva is associated with at least one of the following: contact lens wear, use of ocular prostheses, use of conjunctival sutures, use of prominent scleral buckles, and corneal scarring. In some embodiments, atopic keratoconjunctivitis is accompanied by atopic dermatitis and / or asthma. In some embodiments, herpetic keratoconjunctivitis is caused by or in part by delayed hypersensitivity or inflammatory reactions of the cornea and conjunctiva to antigens expressed by various pathogens. In some embodiments, the pathogen is at least one of the following: bacteria (e.g., Staphylococcus aureus, Streptococcus viridans, Mycobacterium tuberculosis), viruses (e.g., herpes simplex virus), chlamydia, fungi (e.g., Candida albicans), and parasites (e.g., tapeworms such as Hymenolepis microsporum; and nematodes). In some embodiments, the subject does not suffer from any eye disease selected from viral conjunctivitis, bacterial conjunctivitis, chemical conjunctivitis, and dry eye syndrome or dry eye-related conditions. In some embodiments, the subject experiences at least one symptom selected from conjunctival redness, conjunctival edema, conjunctival hyperemia, eyelid redness, eyelid edema, eyelid hyperemia, itchy eye, visible corneal damage, mucus discharge, watery discharge, tearing, photophobia, foreign body sensation, and difficulty opening the eyes before administration of a polypeptide or fragment or variant thereof having at least 70% identity with any of SEQ ID NO: 28, SEQ ID NO: 57, and 62-74. In some embodiments, after administration of at least one dose of a polypeptide or fragment or variant thereof having at least 70% identity with any one of SEQ ID NO: 28, SEQ ID NO: 57, and 62-74, a subject exhibits relief of at least one symptom selected from conjunctival redness, conjunctival edema, conjunctival hyperemia, eyelid redness, eyelid edema, eyelid hyperemia, itchy eyes, visible corneal damage, mucus secretion, watery secretion, tearing, photophobia, foreign body sensation, and difficulty opening the eyes. In some embodiments, after administration of at least one dose of a polypeptide or fragment or variant thereof having at least 70% identity with any one of SEQ ID NO: 28, SEQ ID NO: 57, and 62-74, a subject exhibits improvement in at least one tissue selected from the conjunctiva, cornea, anterior chamber, iris, pupil, vitreous body, and fundus.

[0069] In another aspect, there is provided an artificial polypeptide of formula (I), (II), (III), (IV), (V), (VI), or (VII), or a mutant of artificial polypeptide (I), (II), (III), (IV), or (V), or a polypeptide or fragment or variant thereof having at least 70% identity with any one of SEQ ID NO. 28, SEQ ID NO. 57, and 62-74, for use in the treatment or prevention of allergic conjunctivitis in a subject of need.

[0070] In another aspect, there is provided an artificial polypeptide of formula (I), (II), (III), (IV), (V), (VI), or (VII), or a mutant of artificial polypeptide (I), (II), (III), (IV), or (V), or a polypeptide or fragment or variant thereof having at least 70% identity with any one of SEQ ID NO. 28, SEQ ID NO. 57, and 62-74 for use in the preparation of a medicament for the treatment or prevention of allergic conjunctivitis in a subject of need.

[0071] In some embodiments, allergic conjunctivitis is at least one selected from seasonal allergic conjunctivitis, perennial allergic conjunctivitis, vernal keratoconjunctivitis, giant papillary conjunctivitis, atopic keratoconjunctivitis, and herpetic keratoconjunctivitis. In some embodiments, seasonal allergic conjunctivitis is caused by or partially by a seasonal allergen. In some embodiments, the seasonal allergen is at least one selected from tree pollen, weed pollen, grass pollen, and mold spores. In some embodiments, perennial allergic conjunctivitis is caused by or partially by a perennial allergen. In some embodiments, the perennial allergen is at least one selected from dust mites, cockroaches, and animal dander. In some embodiments, vernal keratoconjunctivitis is at least one selected from palpebral vernal keratoconjunctivitis, limbal vernal keratoconjunctivitis, and mixed vernal keratoconjunctivitis. In some embodiments, giant papillary conjunctivitis is caused by or partially by repeated mechanical irritation of the conjunctiva. In some embodiments, repetitive mechanical irritation of the conjunctiva is associated with at least one of the following: contact lens wear, use of ocular prostheses, use of conjunctival sutures, use of scleral buckles, and corneal scarring. In some embodiments, atopic keratoconjunctivitis is accompanied by atopic dermatitis and / or asthma. In some embodiments, herpetic keratoconjunctivitis is caused by or in part by delayed hypersensitivity or inflammatory response of the cornea and conjunctiva to antigens expressed by various pathogens. (Instructions for Use, Page 19 / 68, 40 CN 121079312 A)In some embodiments, the pathogen is at least one selected from bacteria (e.g., Staphylococcus aureus, Streptococcus viride, Mycobacterium tuberculosis), viruses (e.g., herpes simplex virus), chlamydia, fungi (e.g., Candida albicans), and parasites (e.g., tapeworms such as Hymenolepis microsporum; and nematodes). In some embodiments, the subject does not suffer from any ocular disease selected from viral conjunctivitis, bacterial conjunctivitis, chemical conjunctivitis, and dry eye syndrome or dry eye-related conditions. In some embodiments, the subject experiences at least one symptom prior to administration of an artificial polypeptide of formula (I), (II), (III), (IV), (V), (VI), or (VII), or a mutant of an artificial polypeptide of formula (I), (II), (III), (IV), or (V), or a polypeptide or fragment or variant thereof having at least 70% identity with any one of SEQ ID NO. 28, SEQ ID NO. 57, and 62-74, said symptom being selected from conjunctival redness, conjunctival edema, conjunctival hyperemia, eyelid redness, eyelid edema, eyelid hyperemia, itchy eyes, visible corneal damage, mucus secretion, watery secretion, tearing, photophobia, foreign body sensation, and difficulty opening the eyes. In some embodiments, after administration of at least one dose of an artificial polypeptide of formula (I), (II), (III), (IV), (V), (VI), or (VII), or a mutant of an artificial polypeptide of formula (I), (II), (III), (IV), or (V), or a polypeptide or fragment or variant thereof having at least 70% identity with any one of SEQ ID NO. 28, SEQ ID NO. 57, and 62-74, a subject shows relief of at least one symptom selected from conjunctival redness, conjunctival edema, conjunctival hyperemia, eyelid redness, eyelid edema, eyelid hyperemia, itchy eyes, visible corneal damage, mucus secretion, watery secretion, tearing, photophobia, foreign body sensation, and difficulty opening the eyes. In some embodiments, the subject shows improvement in at least one tissue selected from the conjunctiva, cornea, anterior chamber, iris, pupil, vitreous body, and fundus after administration of at least one dose of an artificial polypeptide of formula (I), (II), (III), (IV), (V), (VI), or (VII), or a mutant of an artificial polypeptide of formula (I), (II), (III), (IV), or (V), or a polypeptide or fragment or variant thereof having at least 70% identity with any one of SEQ ID NO. 28, SEQ ID NO. 57, and 62-74.

[0072] Other aspects and advantages of this disclosure will become apparent to those skilled in the art from the following detailed description, in which only exemplary embodiments of the disclosure are shown and described. As will be appreciated, the disclosure is capable of having other different embodiments, and certain details thereof can be modified in various obvious ways without departing from the disclosure.Therefore, this description should be considered illustrative rather than restrictive.

[0073] All publications, patents, and patent applications mentioned in this specification are incorporated herein by reference to the extent that each individual publication, patent, or patent application is specifically and individually indicated to be incorporated by reference.

[0074] Various features of this disclosure are set forth in detail in the appended claims. A better understanding of the features and advantages of this disclosure will be obtained by referring to the following detailed description and accompanying drawings, which illustrate exemplary embodiments utilizing the principles of the invention, in which: Figure 1 shows the inflammation scores of the mice in each group on day 14, as measured according to Example 2.

[0075] Figure 2 shows the number of scratches of the mice in each group on day 14, as measured according to Example 2.

[0076] Definitions Unless otherwise specified, the following terms as used herein have the meanings assigned to them.

[0077] Unless the context clearly indicates otherwise, the singular forms “an” and “the” as used in the specification and claims include a plurality of indicators. For example, the term “a cell” includes a plurality of cells, including mixtures thereof.

[0078] As used herein, the terms “comprising,” “including,” “containing,” and variations thereof are intended to be open transitional phrases that do not exclude the possibility of additional substances or methods. When such terms are used to describe a pharmaceutical composition, formulation, kit, use, or method of this disclosure, they also cover the case where the pharmaceutical composition, formulation, kit, use, or method is composed of said substance or method. For example, the expression “the solvent contains water” also includes the case where the solvent is composed of water, i.e., the solvent contains only water. In the context of this disclosure, the term “composed of” is intended to be a closed transitional phrase that excludes the possibility of additional substances or methods.

[0079] As used herein, unless otherwise indicated, the scope as described in this disclosure is intended to explicitly disclose each endpoint of the scope and each integer included in the scope. For example, "X is a portion containing 40 to 65 amino acids" means that the number of amino acids in portion X can be 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, or 65. For example, "Y is a portion containing 10 to 50 amino acids" means that the number of amino acids in portion Y can be 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, or 50.Additionally, any subranges consisting of these integers are intended to be included within the scope of this disclosure. Thus, “X is a portion containing 40 to 65 amino acids” is considered to explicitly disclose a subrange, such as “X is a portion containing 41 to 64 amino acids,” “X is a portion containing 42 to 63 amino acids,” “X is a portion containing 43 to 62 amino acids,” etc.

[0080] The terms “about” or “approximately” herein mean that a specific value, as determined by one person of ordinary skill in the art, is within an acceptable range of error, which will depend in part on how the value is measured or determined, i.e., the limitations of the measurement system. For example, according to practice in the art, “about” may mean within one or more standard deviations. Alternatively, “about” may mean a range of up to 20%, up to 10%, up to 5%, or up to 1% of a given value. In cases where specific values ​​are described in this application and claims, unless otherwise stated, the terms “about” or “approximately” should be assumed to mean that the specific value is within an acceptable range of error.

[0081] The term “optional” means that the event described below may or may not occur, and the description includes both the occurrence of the event or situation and the absence thereof.

[0082] The terms “polypeptide,” “peptide,” and “protein” are used interchangeably herein to refer to an amino acid polymer of any length. The polymer may be linear or branched, may contain modified amino acids, and may be interrupted by non-amino acid components. The term also covers modified amino acid polymers; for example, disulfide bond formation, glycosylation, esterification, acetylation, phosphorylation, or any other operation, such as conjugation with a labeled component.

[0083] When applied to proteins, as used herein, the term “fragment” refers to a truncated form of a native bioactive protein that may or may not retain at least a portion of its therapeutic and / or biological activity.

[0084] When applied to proteins, as used herein, the term “variant” refers to a protein that has sequence homology with a native bioactive protein and retains at least a portion of the therapeutic and / or biological activity of the bioactive protein. For example, variant proteins may share at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% amino acid sequence identity with a reference bioactive protein.

[0085] As used herein, the term “amino acid (AA)” refers to natural and / or non-natural or synthetic amino acids, including but not limited to glycine and D or L optical isomers, as well as amino acid analogs and peptide mimics. Standard single-letter or three-letter codes are used to designate amino acids.

[0086] The term "natural L-amino acid" refers to the L-optical isomers of glycine (G), proline (P), alanine (A), valine (V), leucine (L), isoleucine (I), methionine (M), cysteine ​​(C), phenylalanine (F), tyrosine (Y), tryptophan (W), histidine (H), lysine (K), arginine (R), glutamine (Q), asparagine (N), glutamic acid (E), aspartic acid (D), serine (S), and threonine (T).

[0087] The terms "hydrophilic" and "hydrophobic" refer to the degree of affinity of a substance for water. Hydrophilic substances have a strong affinity for water, tend to dissolve in water, mix with water, or be wetted by water, while hydrophobic substances have essentially no affinity for water, tend to repel water and do not absorb water, and tend to be insoluble in water, unmixable with water, or unwetted by water. Amino acids can be characterized by their hydrophobicity. Examples of “hydrophilic amino acids” are arginine, lysine, threonine, alanine, asparagine, and glutamine. Of particular interest are the hydrophilic amino acids aspartic acid, glutamic acid, serine, and glycine. In some embodiments, “hydrophilic amino acids” refers to arginine, lysine, threonine, alanine, asparagine, glutamine, aspartic acid, glutamic acid, serine, and glycine. Examples of “hydrophobic amino acids” are tryptophan, tyrosine, phenylalanine, methionine, leucine, isoleucine, and valine. In some embodiments, “hydrophobic amino acid” refers to tryptophan, tyrosine, phenylalanine, methionine, leucine, isoleucine, and valine.

[0088] “Host cell” includes a single cell or cell culture that can serve as or has served as a recipient of the subject matter carrier. Host cell includes progeny of a single host cell. Progeny may not necessarily be identical to the original parent cell (in morphology or in terms of the genome of total DNA complement).

[0089] “conjugated,” “linked,” “fused,” and “fusion” are used interchangeably herein. These terms refer to the joining of two additional chemical elements or components together by any means, including chemical conjugation or recombination.

[0090] The terms “polynucleotide,” “nucleic acid,” “nucleotide,” and “oligonucleotide” are used interchangeably. They refer to polymeric forms of nucleotides of any length, whether deoxyribonucleotides or ribonucleotides, or analogs thereof. Polynucleotides can have any three-dimensional structure and can perform any known or unknown function.The following are non-limiting examples of polynucleotides: coding or non-coding regions of genes or gene fragments, loci defined by linkage analysis, exons, introns, messenger RNA (mRNA), transfer RNA, ribosomal RNA, ribozymes, cDNA, recombinant polynucleotides, branched polynucleotides, plasmids, vectors, isolated DNA of any sequence, isolated RNA of any sequence, nucleic acid probes, and primers. Polynucleotides may contain modified nucleotides, such as methylated nucleotides and nucleotide analogs. If present, the nucleotide structure may be modified before or after polymer assembly. The nucleotide sequence may be interrupted by non-nucleotide components. Polynucleotides may be further modified after polymerization, such as conjugated with labeled components.

[0091] The term "complement of a polynucleotide" means that the polynucleotide molecule has a complementary base sequence and reverse orientation compared to the reference sequence, such that it can hybridize with the reference sequence with complete fidelity.

[0092] When applied to polynucleotides, the term “recombinant” means that the polynucleotide is the product of various combinations of in vitro cloning, restriction enzyme digestion and / or ligation steps, and other steps that produce a construct that can potentially be expressed in a host cell.

[0093] The term “homology” or “homologous” refers to the sequence similarity or interchangeability between two or more polynucleotide sequences or two or more polypeptide sequences. When using a program such as BestFit to determine sequence identity, similarity, or homology between two different amino acid sequences, default settings can be used, or an appropriate scoring matrix, such as blosum45 or blosum80, can be selected to optimize the identity, similarity, or homology score. Preferably, homologous polynucleotides are those that hybridize under stringent conditions as defined herein and have at least 70%, preferably at least 80%, more preferably at least 90%, more preferably 95%, more preferably 97%, more preferably 98%, and even more preferably 99% sequence identity with those sequences.

[0094] When applied to polynucleotide sequences, the terms “identity percentage” and “identity %” refer to the percentage of residue matches between at least two polynucleotide sequences aligned using a normalization algorithm. This algorithm inserts gaps in the compared sequences in a normalized and reproducible manner to optimize the alignment between the two sequences and thus enable a more meaningful comparison. The identity percentage can be measured over the entire length of the polynucleotide sequence as defined (e.g., as defined by a specific SEQ ID number), or over a shorter length, for example, over the length of a fragment obtained from a larger defined polynucleotide sequence, such as a fragment of at least 45, at least 60, at least 90, at least 120, at least 150, at least 210, or at least 450 consecutive residues.Such lengths are merely exemplary, and it should be understood that any fragment length supported by the sequences shown herein in the tables, figures, or sequence listings can be used to describe lengths from which a percentage of identity can be measured.

[0095] The “percentage of amino acid sequence identity (%)” for a polypeptide sequence identified herein is defined as the percentage of amino acid residues in the query sequence that are identical to amino acid residues in a second reference polypeptide sequence or a portion thereof, after alignment of the sequences and introduction of gaps (if necessary) to achieve the maximum percentage of sequence identity without considering any conservative substitutions as part of the sequence identity. Alignment used to determine the percentage of amino acid sequence identity can be performed in a variety of ways well known in the art, for example, using publicly available computer software such as BLAST, BLAST-2, ALIGN, or Megalign (DNASTAR) software. Those skilled in the art can determine appropriate parameters for measuring alignment, including any algorithms required to achieve maximum alignment over the full length of the sequences being compared. The percentage of identity can be measured over the entire length of a defined polypeptide sequence (e.g., as defined by a specific SEQ ID number), or over a shorter length, such as over the length of a fragment taken from a larger defined polypeptide sequence, for example, a fragment of at least 15, at least 20, at least 30, at least 40, at least 50, at least 70, or at least 150 consecutive residues. Such lengths are merely exemplary and it should be understood that any fragment length supported by the sequences shown herein in the tables, figures, or sequence listings can be used to describe lengths over which the percentage of identity can be measured.

[0096] A “vector” is a nucleic acid molecule that preferably self-replicates in a suitable host, which transfers an inserted nucleic acid molecule into a host cell and / or causes it to transfer between host cells. The term includes vectors primarily used for inserting DNA or RNA into cells, replication vectors primarily used for replicating DNA or RNA, and expression vectors for DNA or RNA transcription and / or translation. Vectors that provide more than one of the above functions are also included. An “expression vector” is a polynucleotide that, when introduced into a suitable host cell, can be transcribed and translated into a polypeptide. “Expression system” generally means a suitable host cell containing an expression vector that can be used to produce the desired expression product.

[0097] The term “physiological conditions” refers to a set of conditions in a living host and in vitro conditions that simulate those conditions in a living object, including temperature, salt concentration, and pH. Many physiologically relevant conditions have been established for in vitro assays. Typically, physiological buffers contain a physiological concentration of salt and are adjusted to a neutral pH, ranging from about 6.5 to about 7.8, and preferably from about 7.0 to about 7.5. Sambrook et al. (1989) listed a variety of physiological buffers. Physiologically relevant temperatures range from about 25 °C to about 38 °C, and preferably from about 35 °C to about 37 °C.

[0098] As used herein, the term “antagonist” includes any molecule that partially or completely blocks, inhibits, or neutralizes the biological activity of the natural polypeptides disclosed herein. Methods for identifying antagonists of polypeptides may include contacting a natural polypeptide with a candidate antagonist molecule and measuring a detectable change in one or more biological activities typically associated with the natural polypeptide. In the context of this disclosure, antagonists may include proteins, nucleic acids, carbohydrates, antibodies, or any other molecule that reduces the activity of a biologically active protein.

[0099] The term “agonist” is used in the broadest sense and includes any molecule that mimics the biological activity of the natural polypeptides disclosed herein. Suitable agonist molecules particularly include agonist antibodies or antibody fragments, fragments or amino acid sequence variants of natural polypeptides, peptides, small organic molecules, etc. Methods for identifying agonists of natural polypeptides may include contacting a natural polypeptide with a candidate agonist molecule and measuring a detectable change in one or more biological activities typically associated with the natural polypeptide.

[0100] The term “activity” used herein for purposes of this document means an action or effect consistent with the component of a fusion protein and the component of a corresponding natural bioactive protein, wherein “bioactivity” means a biological function or effect in vitro or in vivo, including but not limited to receptor binding, antagonist activity, agonist activity, or cellular or physiological response.

[0101] As used herein, “treatment” or “curative,” “relief,” and “improvement” are used interchangeably. These terms refer to methods for obtaining beneficial or desired results, including but not limited to therapeutic benefits and / or preventive benefits. A “therapeutic benefit” means the eradication or improvement of an underlying condition being treated. Moreover, a therapeutic benefit is achieved by eradicating or improving one or more physiological symptoms associated with an underlying disease condition, resulting in an improvement observed in the subject, although the subject may still be troubled by the underlying condition. For preventive benefits, the composition may be administered to a subject at risk of developing a specific disease condition, or to a subject reporting one or more physiological symptoms of a disease, even if a diagnosis of the disease may not have been made.

[0102] The term “therapeutic effect” refers to the physiological effect caused by the polypeptides of this disclosure, including but not limited to curing, alleviating, improving or preventing disease conditions in humans or other animals, or otherwise enhancing the physical or mental health of humans or animals. The determination of a therapeutically effective amount, especially in accordance with the detailed disclosure provided herein, is entirely within the capabilities of those skilled in the art.

[0103] The term “effective amount” refers to the amount of a bioactive protein, alone or as part of a fusion protein composition, that, when administered to a subject in one or repeated doses, is capable of producing any detectable beneficial effect on any symptom, aspect, measurement parameter, or characteristic of a disease state or condition. Such an effect need not be absolute to be beneficial. A disease state can refer to a symptom or disease.

[0104] The term “pharmaceutically acceptable” means those compounds, materials, compositions, formulations, or dosage forms that, within the bounds of reasonable medical judgment, are suitable for use in contact with tissues of humans and other animals without excessive toxicity, irritation, allergic reactions, or other problems or complications, in proportion to a reasonable benefit / risk ratio.

[0105] The terms “formulation” and “dosage form” are used interchangeably and refer to a pharmaceutical composition formulated according to clinical requirements, in a form that can be directly applied to the subject of need for preventive or therapeutic purposes.

[0106] The term “pharmaceuticalally acceptable excipient” means a pharmaceutically acceptable material, carrier, or medium used in the preparation of a formulation or dosage form according to this disclosure. Each excipient must be “acceptable” in terms of compatibility with other components in the formulation or dosage form and harmless to the patient.

[0107] As used herein, the terms “subject,” “individual,” or “patient” mean any animal that can be used with respect to this disclosure, including but not limited to humans, primates, rodents, canines, felines, horses, sheep, pigs, etc.

[0108] The terms “administer,” “administered,” “administers,” and “dosing” are used interchangeably and are defined as providing a compound, composition, formulation, and / or dosage form according to this disclosure to a subject in need via a route known in the art, including but not limited to oral, buccal, topical, transmucosal, transdermal, rectal, and parenteral administration routes. In some embodiments, an oral administration route is used. In some embodiments, a parenteral administration route is used, including intravenous, intra-arterial, intramuscular, subcutaneous, intraosseous, and intraperitoneal routes. In some embodiments, a topical administration route is used.

[0109] As used herein, the term “in vivo” refers to an event that occurs within the body of the subject.

[0110] As used herein, the term “in vitro” refers to an event that occurs outside the body of the subject. In some embodiments, an in vitro assay covers any assay performed outside the subject assay. An in vitro assay covers cell-based assays using live or dead cells. An in vitro assay also covers cell-free assays that do not use intact cells.

[0111] As used herein, the term "allergic conjunctivitis" refers to a class of inflammatory diseases caused by a hypersensitive reaction of the conjunctiva to various allergens. Some common signs and symptoms of allergic conjunctivitis include conjunctival redness, edema or hyperemia, eyelid redness, edema or hyperemia, itchy eyes, visible corneal damage, mucus discharge, watery discharge, tearing, photophobia, foreign body sensation, and difficulty opening the eyes. Other reported symptoms include itchy nose, sneezing, coughing, transient blurred vision, difficulty concentrating, decreased productivity, and fatigue.

[0112] The term “seasonal allergic conjunctivitis” is the most common type of allergic conjunctivitis associated with seasonal allergies that typically occur in the spring and summer, and sometimes in the fall. Seasonal allergic conjunctivitis is thought to be caused, or partially caused, by seasonal allergens such as tree pollen, weed pollen, grass pollen, and mold spores.

[0113] The term “perennial allergic conjunctivitis” refers to a mild, chronic allergic conjunctivitis that persists throughout the year. Perennial allergic conjunctivitis is thought to be caused, or partially caused, by perennial allergens, which are allergens present in the environment (usually indoors) throughout the year, such as dust mites, cockroaches, and animal dander.

[0114] The term “vernal keratoconjunctivitis” refers to a recurrent, bilateral, and self-limiting allergic conjunctivitis with a periodic seasonal incidence. Vernal keratoconjunctivitis is clinically further divided into three subtypes: eyelid vernal keratoconjunctivitis, limbal vernal keratoconjunctivitis, and mixed vernal keratoconjunctivitis. Vernal keratoconjunctivitis is thought to be caused, or partially caused, by dust mites, pollen, and / or animal dander. However, for most patients, it is often difficult to identify the allergen.

[0115] The term “giant papillary conjunctivitis” refers to an allergic conjunctivitis caused, or partially caused, by repetitive mechanical irritation of the conjunctiva. For example, repetitive mechanical irritation of the conjunctiva can be associated with contact lens wear, use of ocular prostheses, use of conjunctival sutures, use of prominent scleral buckles, and corneal scarring.

[0116] The term “atopic keratoconjunctivitis” refers to a chronic (long-term) allergic conjunctivitis that affects patients with atopic dermatitis. Atopic keratoconjunctivitis is often accompanied by atopic dermatitis and / or asthma.

[0117] The term “vesicular keratoconjunctivitis” refers to an allergic conjunctivitis caused, or partially caused, by a delayed hypersensitivity or inflammatory response of the cornea and conjunctiva to antigens expressed by various pathogens. Triggering antigens are typically bacterial proteins (particularly those from Staphylococcus aureus, Streptococcus viridans, Mycobacterium tuberculosis, etc.), but can also be components (e.g., proteins) of viruses (e.g., herpes simplex virus), chlamydia, fungi (particularly Candida, such as Candida albicans), or parasites (e.g., tapeworms, such as Hymenolepis microsporum; and nematodes). Treatment methods and therapeutic uses

[0118] In one aspect, a method is provided for treating or preventing allergic conjunctivitis in a subject in need, comprising administering to the subject an effective amount of an artificial polypeptide of formula (I): X-Y (I), wherein X is a portion comprising a sequence having at least 80% identity with SEQ ID NO: 1, and Y is a portion comprising 10 to 50 amino acids, at least 50% of which are selected from I, V, L, F, C, M, and A; wherein the total number of cysteine ​​(C) contained in Y is less than 5.

[0119] In some embodiments, X of formula (I) may be a hydrophilic portion, wherein at least 50% is selected from R, K, N, D, Q, E, and H. In some embodiments, X of formula (I) may be a hydrophilic portion, wherein at least 55% is selected from R, K, N, D, Q, E, and H. In some embodiments, X of formula (I) may be a hydrophilic portion, wherein at least 60% is selected from R, K, N, D, Q, E, and H. In some embodiments, X of formula (I) may be a hydrophilic portion, wherein at least 65% is selected from R, K, N, D, Q, E, and H. In some embodiments, X of formula (I) may be a hydrophilic portion, wherein at least 70% is selected from R, K, N, D, Q, E, and H. In some embodiments, X of formula (I) may be a hydrophilic portion, wherein at least 75% is selected from R, K, N, D, Q, E, and H. In some embodiments, X of formula (I) may be a hydrophilic portion, wherein at least 80% is selected from R, K, N, D, Q, E, and H. In some embodiments, X of formula (I) may be a hydrophilic portion, wherein at least 85% is selected from R, K, N, D, Q, E, and H. In some embodiments, X of formula (I) may be a hydrophilic portion, wherein at least 90% is selected from R, K, N, D, Q, E, and H.

[0120] In some embodiments, X of formula (I) may be a portion comprising a sequence having at least 80% identity with SEQ ID NO: 1. In some embodiments, X is a portion comprising a sequence having at least 85% identity with SEQ ID NO: 1. In some embodiments, X is a portion comprising a sequence having at least 90% identity with SEQ ID NO: 1. In some embodiments, X is a portion comprising a sequence having at least 95% identity with SEQ ID NO: 1. In some embodiments, X is a portion comprising a sequence having at least 96%, at least 97%, at least 98%, or at least 99% identity with SEQ ID NO: 1. In some embodiments, X is a portion comprising the sequence of SEQ ID NO: 1. In some embodiments, X is a portion that is precisely the sequence of SEQ ID NO: 1.

[0121] In some embodiments, Y of formula (I) may be a hydrophobic portion, wherein at least 50% is selected from I, V, L, F, C, M, and A. In some embodiments, Y of formula (I) may be a hydrophobic portion, wherein at least 55% is selected from I, V, L, F, C, M, and A. In some embodiments, Y of formula (I) may be a hydrophobic portion, wherein at least 60% is selected from I, V, L, F, C, M, and A. In some embodiments, Y of formula (I) may be a hydrophobic portion, wherein at least 65% is selected from I, V, L, F, C, M, and A.In some embodiments, Y in formula (I) may be a hydrophobic portion, wherein at least 70% is selected from I, V, L, F, C, M, and A. In some embodiments, Y in formula (I) may be a hydrophobic portion, wherein at least 75% is selected from I, V, L, F, C, M, and A. In some embodiments, Y in formula (I) may be a hydrophobic portion, wherein at least 80% is selected from I, V, L, F, C, M, and A. In some embodiments, Y in formula (I) may be a hydrophobic portion, wherein at least 85% is selected from I, V, L, F, C, M, and A. In some embodiments, Y in formula (I) may be a hydrophobic portion, wherein at least 90% is selected from I, V, L, F, C, M, and A.

[0122] In some embodiments, Y in formula (I) may be a portion comprising 10 to 50 amino acids, and the total number of hydrophobic amino acids in Y is 5. In some embodiments, Y in formula (I) may be a portion containing 10 to 50 amino acids, and the total number of hydrophobic amino acids in Y is greater than 5. In some embodiments, Y in formula (I) may be a portion containing 10 to 50 amino acids, and the total number of hydrophobic amino acids in Y is 6. In some embodiments, Y in formula (I) may be a portion containing 10 to 50 amino acids, and the total number of hydrophobic amino acids in Y is greater than 6. In some embodiments, Y in formula (I) may be a portion containing 10 to 50 amino acids, and the total number of hydrophobic amino acids in Y is 7. In some embodiments, Y in formula (I) may be a portion containing 10 to 50 amino acids, and the total number of hydrophobic amino acids in Y is greater than 7. In some embodiments, Y in formula (I) may be a portion containing 10 to 50 amino acids, and the total number of hydrophobic amino acids in Y is 8. In some embodiments, Y in formula (I) may be a portion containing 10 to 50 amino acids, and the total number of hydrophobic amino acids in Y is greater than 8. In some embodiments, Y in formula (I) may be a portion containing 10 to 50 amino acids, and the total number of hydrophobic amino acids in Y is 9. In some embodiments, Y in formula (I) may be a portion containing 10 to 50 amino acids, and the total number of hydrophobic amino acids in Y is greater than 9. In some embodiments, Y in formula (I) may be a portion containing 10 to 50 amino acids, and the total number of hydrophobic amino acids in Y is 10. In some embodiments, Y in formula (I) may be a portion containing 10 to 50 amino acids, and the total number of hydrophobic amino acids in Y is greater than 10. In some embodiments, Y in formula (I) may be a portion containing 10 to 50 amino acids, and the total number of hydrophobic amino acids in Y is 11. In some embodiments, Y in formula (I) may be a portion containing 10 to 50 amino acids, and the total number of hydrophobic amino acids in Y is greater than 11.In some embodiments, Y in formula (I) may be a portion containing 10 to 50 amino acids, and the total number of hydrophobic amino acids in Y is 12. In some embodiments, Y in formula (I) may be a portion containing 10 to 50 amino acids, and the total number of hydrophobic amino acids in Y is greater than 12. In some embodiments, Y in formula (I) may be a portion containing 10 to 50 amino acids, and the total number of hydrophobic amino acids in Y is 13. In some embodiments, Y in formula (I) may be a portion containing 10 to 50 amino acids, and the total number of hydrophobic amino acids in Y is greater than 13. In some embodiments, Y in formula (I) may be a portion containing 10 to 50 amino acids, and the total number of hydrophobic amino acids in Y is 14. In some embodiments, Y in formula (I) may be a portion containing 10 to 50 amino acids, and the total number of hydrophobic amino acids in Y is greater than 14. In some embodiments, Y in formula (I) may be a portion containing 10 to 50 amino acids, and the total number of hydrophobic amino acids in Y is 15. In some embodiments, Y in formula (I) may be a portion containing 10 to 50 amino acids, and the total number of hydrophobic amino acids in Y is greater than 15. Specification 26 / 68 pages 47 CN 121079312 A

[0123] In some embodiments, Y in formula (I) may be a portion containing 10 to 50 amino acids, and the total number of I, V, L, F, C, M, and A in Y is 5. In some embodiments, Y in formula (I) may be a portion containing 10 to 50 amino acids, and the total number of I, V, L, F, C, M, and A in Y is greater than 5. In some embodiments, Y in formula (I) may be a portion containing 10 to 50 amino acids, and the total number of I, V, L, F, C, M, and A in Y is 6. In some embodiments, Y in formula (I) may be a portion containing 10 to 50 amino acids, and the total number of I, V, L, F, C, M, and A in Y is greater than 6. In some embodiments, Y in formula (I) may be a portion containing 10 to 50 amino acids, and the total number of I, V, L, F, C, M, and A in Y is 7. In some embodiments, Y in formula (I) may be a portion containing 10 to 50 amino acids, and the total number of I, V, L, F, C, M, and A in Y is greater than 7. In some embodiments, Y in formula (I) may be a portion containing 10 to 50 amino acids, and the total number of I, V, L, F, C, M, and A in Y is 8. In some embodiments, Y in formula (I) may be a portion containing 10 to 50 amino acids, and the total number of I, V, L, F, C, M, and A in Y is greater than 8. In some embodiments, Y in formula (I) may be a portion containing 10 to 50 amino acids, and the total number of I, V, L, F, C, M, and A in Y is 9.In some embodiments, Y in formula (I) may be a portion containing 10 to 50 amino acids, and the total number of I, V, L, F, C, M, and A in Y is greater than 9. In some embodiments, Y in formula (I) may be a portion containing 10 to 50 amino acids, and the total number of I, V, L, F, C, M, and A in Y is 10. In some embodiments, Y in formula (I) may be a portion containing 10 to 50 amino acids, and the total number of I, V, L, F, C, M, and A in Y is greater than 10. In some embodiments, Y in formula (I) may be a portion containing 10 to 50 amino acids, and the total number of I, V, L, F, C, M, and A in Y is 11. In some embodiments, Y in formula (I) may be a portion containing 10 to 50 amino acids, and the total number of I, V, L, F, C, M, and A in Y is greater than 11. In some embodiments, Y in formula (I) may be a portion containing 10 to 50 amino acids, and the total number of I, V, L, F, C, M, and A in Y is 12. In some embodiments, Y in formula (I) may be a portion containing 10 to 50 amino acids, and the total number of I, V, L, F, C, M, and A in Y is greater than 12. In some embodiments, Y in formula (I) may be a portion containing 10 to 50 amino acids, and the total number of I, V, L, F, C, M, and A in Y is 13. In some embodiments, Y in formula (I) may be a portion containing 10 to 50 amino acids, and the total number of I, V, L, F, C, M, and A in Y is greater than 13. In some embodiments, Y in formula (I) may be a portion containing 10 to 50 amino acids, and the total number of I, V, L, F, C, M, and A in Y is 14. In some embodiments, Y in formula (I) may be a portion containing 10 to 50 amino acids, and the total number of I, V, L, F, C, M, and A of Y is greater than 14. In some embodiments, Y in formula (I) may be a portion containing 10 to 50 amino acids, and the total number of I, V, L, F, C, M, and A of Y is 15. In some embodiments, Y in formula (I) may be a portion containing 10 to 50 amino acids, and the total number of I, V, L, F, C, M, and A of Y is greater than 15.

[0124] In some embodiments, Y in formula (I) may be a portion containing 10 to 50 amino acids, and the total number of cysteine ​​(C) of Y is 5. In some embodiments, Y in formula (I) may be a portion containing 10 to 50 amino acids, and the total number of cysteine ​​(C) of Y is less than 5. In some embodiments, Y in formula (I) may be a portion containing 10 to 50 amino acids, and the total number of cysteine ​​(C) of Y is 4. In some implementations, Y in formula (I) may be a portion containing 10 to 50 amino acids, and the total number of cysteine ​​(C) in Y is less than 4.In some embodiments, Y in formula (I) may be a portion containing 10 to 50 amino acids, and the total number of cysteine ​​(C) residues in Y is 3. In some embodiments, Y in formula (I) may be a portion containing 10 to 50 amino acids, and the total number of cysteine ​​(C) residues in Y is less than 3. In some embodiments, Y in formula (I) may be a portion containing 10 to 50 amino acids, and the total number of cysteine ​​(C) residues in Y is 2. In some embodiments, Y in formula (I) may be a portion containing 10 to 50 amino acids, and the total number of cysteine ​​(C) residues in Y is less than 2. In some embodiments, Y in formula (I) may be a portion containing 10 to 50 amino acids, and the total number of cysteine ​​(C) residues in Y is 1. In some embodiments, Y in formula (I) may be a portion containing 10 to 50 amino acids, and the total number of cysteine ​​(C) residues in Y is less than 1. In some embodiments, Y in formula (I) may be a portion containing 10 to 50 amino acids, and the total number of cysteine ​​(C) residues in Y is 0. Specification 27 / 68 pages 48 CN 121079312 A

[0125] In some embodiments, the total number of hydrophilic amino acids in Y of formula (I) is 5. In some embodiments, the total number of hydrophilic amino acids in Y of formula (I) is no more than 5. In some embodiments, the total number of hydrophilic amino acids in Y of formula (I) is 4. In some embodiments, the total number of hydrophilic amino acids in Y of formula (I) is no more than 4. In some embodiments, the total number of hydrophilic amino acids in Y of formula (I) is 3. In some embodiments, the total number of hydrophilic amino acids in Y of formula (I) is no more than 3. In some embodiments, the total number of hydrophilic amino acids in Y of formula (I) is 2. In some embodiments, the total number of hydrophilic amino acids in Y of formula (I) is no more than 2. In some embodiments, the total number of hydrophilic amino acids in Y of formula (I) is 1. In some embodiments, the total number of hydrophilic amino acids in Y of formula (I) is no more than 1.

[0126] In some embodiments, the total number of R, K, N, D, Q, E, and H in Y of formula (I) is 5. In some embodiments, the total number of R, K, N, D, Q, E, and H in Y of formula (I) is no more than 5. In some embodiments, the total number of hydrophilic amino acids in Y of formula (I) is 4. In some embodiments, the total number of R, K, N, D, Q, E, and H in Y of formula (I) is no more than 4. In some embodiments, the total number of R, K, N, D, Q, E, and H in Y of formula (I) is 3. In some embodiments, the total number of R, K, N, D, Q, E, and H in Y of formula (I) is no more than 3. In some embodiments, the total number of R, K, N, D, Q, E, and H in Y of formula (I) is 2. In some embodiments, the total number of R, K, N, D, Q, E, and H in Y of formula (I) is no more than 2.In some embodiments, the total number of R, K, N, D, Q, E, and H in Y of formula (I) is 1. In some embodiments, the total number of R, K, N, D, Q, E, and H in Y of formula (I) is no more than 1.

[0127] In some embodiments of the artificial polypeptide, X of formula (I) comprises a sequence having at least 70% identity with any one of SEQ ID NO: 81-83. In some embodiments of the artificial polypeptide, X of formula (I) comprises a sequence having at least 75% identity with any one of SEQ ID NO: 81-83. In some embodiments of the artificial polypeptide, X of formula (I) comprises a sequence having at least 80% identity with any one of SEQ ID NO: 81-83. In some embodiments of the artificial polypeptide, X of formula (I) comprises a sequence having at least 85% identity with any one of SEQ ID NO: 81-83. In some embodiments of the artificial polypeptide, X of formula (I) comprises a sequence having at least 90% identity with any one of SEQ ID NO: 81-83. In some embodiments of the artificial polypeptide, X of formula (I) comprises a sequence having at least 95% identity with any one of SEQ ID NO: 81-83. In some embodiments of the artificial polypeptide, X of formula (I) comprises a sequence having at least 96%, at least 97%, at least 98%, or at least 99% identity with any one of SEQ ID NO: 81-83. In some embodiments of the artificial polypeptide, X of formula (I) comprises a sequence selected from any one of SEQ ID NO: 81-83. In some embodiments of the artificial polypeptide, X of formula (I) is a sequence selected from any one of SEQ ID NO: 81-83.

[0128] In some embodiments of the artificial polypeptide, Y of formula (I) comprises a sequence having at least 70% identity with any one of SEQ ID NO: 3-15, 58-61, and 84-85. In some embodiments of the artificial polypeptide, Y of formula (I) comprises a sequence having at least 75% identity with any one of SEQ ID NO: 3-15, 58-61, and 84-85. In some embodiments of the artificial polypeptide, the Y of formula (I) comprises a sequence having at least 80% identity with any one of SEQ ID NO: 3-15, 58-61, and 84-85. In some embodiments of the artificial polypeptide, the Y of formula (I) comprises a sequence having at least 85% identity with any one of SEQ ID NO: 3-15, 58-61, and 84-85.In some embodiments of the artificial polypeptide, the Y of formula (I) comprises a sequence having at least 90% identity with any one of SEQ ID NO: 3-15, 58-61, and 84-85. In some embodiments of the artificial polypeptide, the Y of formula (I) comprises a sequence having at least 95% identity with any one of SEQ ID NO: 3-15, 58-61, and 84-85. In some embodiments of the artificial polypeptide, the Y of formula (I) comprises a sequence having at least 96%, at least 97%, at least 98%, or at least 99% identity with any one of SEQ ID NO: 3-15, 58-61, and 84-85. In some embodiments of the artificial polypeptide, the Y of formula (I) is a sequence selected from any one of SEQ ID NO: 3-15, 58-61, and 84-85. Specification 28 / 68 pages 49 CN 121079312 A

[0129] In some embodiments of the artificial polypeptide of formula (I), the polypeptide comprises a sequence having at least 70% identity with any one of SEQ ID NO: 29-41, 54-57, 75 and 91-95. In some embodiments of the artificial polypeptide of formula (I), the polypeptide comprises a sequence having at least 75% identity with any one of SEQ ID NO: 29-41, 54-57, 75 and 91-95. In some embodiments of the artificial polypeptide of formula (I), the polypeptide comprises a sequence having at least 80% identity with any one of SEQ ID NO: 29-41, 54-57, 75 and 91-95. In some embodiments of the artificial polypeptide of formula (I), the polypeptide comprises a sequence having at least 85% identity with any one of SEQ ID NO: 29-41, 54-57, 75 and 91-95. In some embodiments of the artificial polypeptide of formula (I), the polypeptide comprises a sequence having at least 90% identity with any one of SEQ ID NO: 29-41, 54-57, 75, and 91-95. In some embodiments of the artificial polypeptide of formula (I), the polypeptide comprises a sequence having at least 95% identity with any one of SEQ ID NO: 29-41, 54-57, 75, and 91-95. In some embodiments of the artificial polypeptide of formula (I), the polypeptide comprises a sequence having at least 96%, at least 97%, at least 98%, or at least 99% identity with any one of SEQ ID NO: 29-41, 54-57, 75, and 91-95.In some embodiments of the artificial polypeptide of formula (I), the polypeptide comprises a sequence of any one of SEQ ID NO: 29-41, 54-57, 75, and 91-95. In some embodiments of the artificial polypeptide of formula (I), the polypeptide is a sequence of any one of SEQ ID NO: 29-41, 54-57, 75, and 91-95.

[0130] In another aspect, a method for treating or preventing allergic conjunctivitis in a subject in need is provided, comprising administering to the subject an effective amount of the artificial polypeptide of formula (II): X-Y (II), wherein X is a portion comprising a sequence having at least 80% identity with SEQ ID NO: 1, and Y is a portion comprising 10 to 50 amino acids, at least 50% of which are selected from I, V, L, F, C, M, and A; wherein Y comprises a sequence having at most 90% identity with SEQ ID NO: 2.

[0131] In some embodiments, X of formula (II) may be a hydrophilic portion, wherein at least 50% is selected from R, K, N, D, Q, E, and H. In some embodiments, X of formula (II) may be a hydrophilic portion, wherein at least 55% is selected from R, K, N, D, Q, E, and H. In some embodiments, X of formula (I) may be a hydrophilic portion, wherein at least 60% is selected from R, K, N, D, Q, E, and H. In some embodiments, X of formula (II) may be a hydrophilic portion, wherein at least 65% is selected from R, K, N, D, Q, E, and H. In some embodiments, X of formula (II) may be a hydrophilic portion, wherein at least 70% is selected from R, K, N, D, Q, E, and H. In some embodiments, X of formula (II) may be a hydrophilic portion, wherein at least 75% is selected from R, K, N, D, Q, E, and H. In some embodiments, X of formula (II) may be a hydrophilic moiety, wherein at least 80% is selected from R, K, N, D, Q, E, and H. In some embodiments, X of formula (II) may be a hydrophilic moiety, wherein at least 85% is selected from R, K, N, D, Q, E, and H. In some embodiments, X of formula (II) may be a hydrophilic moiety, wherein at least 90% is selected from R, K, N, D, Q, E, and H.

[0132] In some embodiments, X of formula (II) may be a hydrophilic moiety comprising one or more arginines (R). For example, X of formula (II) may be a hydrophilic moiety comprising at least one, at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, or at least ten arginines (R). In some embodiments, X of formula (II) may be a hydrophilic moiety comprising one or more lysines (K).For example, X in formula (II) can be a hydrophilic moiety comprising at least one, at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, or at least ten lysine (K). In some embodiments, X in formula (II) can be a hydrophilic moiety comprising one or more asparagine (N). For example, X in formula (II) can be a hydrophilic moiety comprising at least one, at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, or at least ten asparagine (N). In some embodiments, X in formula (II) can be a hydrophilic moiety comprising one or more aspartic (D). For example, X in formula (II) can be a hydrophilic moiety comprising at least one, at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, or at least ten aspartic (D). In some embodiments, X of formula (II) may be a hydrophilic moiety comprising one or more glutamines (Q). For example, X of formula (II) may be a hydrophilic moiety comprising at least one, at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, or at least ten glutamines (Q). In some embodiments, X of formula (II) may be a hydrophilic moiety comprising one or more glutamic acids (E). For example, X of formula (II) may be a hydrophilic moiety comprising at least one, at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, or at least ten glutamic acids (E). In some embodiments, X of formula (II) may be a hydrophilic moiety comprising one or more histidines (H). For example, X of formula (II) may be a hydrophilic moiety comprising at least one, at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, or at least ten histidines (H).

[0133] In some embodiments, X in formula (II) may be a portion comprising a sequence having at least 80% identity with SEQ ID NO: 1. In some embodiments, X is a portion comprising a sequence having at least 85% identity with SEQ ID NO: 1. In some embodiments, X is a portion comprising a sequence having at least 90% identity with SEQ ID NO: 1. In some embodiments, X is a portion comprising a sequence having at least 95% identity with SEQ ID NO: 1. In some embodiments, X is a portion comprising a sequence having at least 96%, at least 97%, at least 98%, or at least 99% identity with SEQ ID NO: 1. In some embodiments, X is a portion comprising the sequence of SEQ ID NO: 1.In some embodiments, X is a portion of the sequence SEQ ID NO: 1.

[0134] In some embodiments of the artificial polypeptide of formula (II), Y comprises a sequence having up to 50% identity with SEQ ID NO: 2. In some embodiments, Y comprises a sequence having up to 55% identity with SEQ ID NO: 2. In some embodiments, Y comprises a sequence having up to 60% identity with SEQ ID NO: 2. In some embodiments, Y comprises a sequence having up to 65% identity with SEQ ID NO: 2. In some embodiments, Y comprises a sequence having up to 70% identity with SEQ ID NO: 2. In some embodiments, Y comprises a sequence having up to 75% identity with SEQ ID NO: 2. In some embodiments, Y comprises a sequence having up to 80% identity with SEQ ID NO: 2. In some embodiments, Y comprises a sequence having up to 85% identity with SEQ ID NO: 2. In some embodiments, Y comprises a sequence having up to 90% identity with SEQ ID NO: 2.

[0135] In some embodiments of the artificial polypeptide of formula (II), Y comprises a sequence having at least 70% identity with any of SEQ ID NO: 16-18. In some embodiments of the artificial polypeptide, Y comprises a sequence having at least 75% identity with any of SEQ ID NO: 16-18. In some embodiments of the artificial polypeptide, Y comprises a sequence having at least 80% identity with any of SEQ ID NO: 16-18. In some embodiments of the artificial polypeptide, Y comprises a sequence having at least 85% identity with any of SEQ ID NO: 16-18. In some embodiments of the artificial polypeptide, Y comprises a sequence having at least 90% identity with any of SEQ ID NO: 16-18. In some embodiments of the artificial polypeptide, Y comprises a sequence having at least 95% identity with any of SEQ ID NO: 16-18. In some embodiments of the artificial polypeptide, Y comprises a sequence having at least 96%, at least 97%, at least 98%, or at least 99% identity with any of SEQ ID NO: 16-18. In some embodiments of the artificial polypeptide, Y comprises a sequence selected from any one of SEQ ID NO: 16-18. In some embodiments of the artificial polypeptide, Y is a sequence selected from any one of SEQ ID NO: 16-18.

[0136] In some embodiments of the artificial polypeptide of formula (II), the artificial polypeptide comprises a sequence having at least 70% identity with any one of SEQ ID NO: 42-44.In some embodiments of the artificial polypeptide, the artificial polypeptide comprises a sequence having at least 75% identity with any one of SEQ ID NO: 42-44. In some embodiments of the artificial polypeptide, the artificial polypeptide comprises a sequence having at least 80% identity with any one of SEQ ID NO: 42-44. In some embodiments of the artificial polypeptide (see page 30 / 68 of CN 121079312 A), the artificial polypeptide comprises a sequence having at least 85% identity with any one of SEQ ID NO: 42-44. In some embodiments of the artificial polypeptide, the artificial polypeptide comprises a sequence having at least 90% identity with any one of SEQ ID NO: 42-44. In some embodiments of the artificial polypeptide, the artificial polypeptide comprises a sequence having at least 95% identity with any one of SEQ ID NO: 42-44. In some embodiments of the artificial polypeptide, the artificial polypeptide comprises a sequence having at least 96%, at least 97%, at least 98%, or at least 99% identity with any one of SEQ ID NO: 42-44. In some embodiments of the artificial polypeptide, the artificial polypeptide comprises a sequence selected from any one of SEQ ID NO: 42-44. In some embodiments of the artificial polypeptide, the artificial polypeptide is a sequence selected from any one of SEQ ID NO: 42-44.

[0137] In another aspect, a method for treating or preventing allergic conjunctivitis in a subject in need is provided, comprising administering to the subject an effective amount of an artificial polypeptide of formula (III): X-Y(III), wherein X is a portion comprising 40 to 65 amino acids, at least 50% of which are selected from H, R, K, D, Q, N, and E; and Y is a portion comprising a sequence having at least 80% identity with SEQ ID NO: 2, wherein the total number of H, R, K, D, Q, N, and E in X is less than 33.

[0138] In some embodiments, X of formula (III) is a hydrophilic portion, wherein at least 50% is selected from H, R, K, D, Q, N, and E. In some embodiments, X in formula (III) may be a hydrophilic portion, wherein at least 55% is selected from R, K, N, D, Q, E, and H. In some embodiments, X in formula (III) may be a hydrophilic portion, wherein at least 60% is selected from R, K, N, D, Q, E, and H. In some embodiments, X in formula (III) may be a hydrophilic portion, wherein at least 65% is selected from R, K, N, D, Q, E, and H. In some embodiments, X in formula (III) may be a hydrophilic portion, wherein at least 70% is selected from R, K, N, D, Q, E, and H.In some embodiments, X of formula (III) may be a hydrophilic portion, wherein at least 75% is selected from R, K, N, D, Q, E, and H. In some embodiments, X of formula (III) may be a hydrophilic portion, wherein at least 80% is selected from R, K, N, D, Q, E, and H. In some embodiments, X of formula (III) may be a hydrophilic portion, wherein at least 85% is selected from R, K, N, D, Q, E, and H. In some embodiments, X of formula (III) may be a hydrophilic portion, wherein at least 90% is selected from R, K, N, D, Q, E, and H.

[0139] In some embodiments, X of formula (III) is a portion containing 40 to 65 amino acids, and the total number of H, R, K, D, Q, N, and E in X is less than 33. In some embodiments, X of formula (III) is a portion containing 40 to 65 amino acids, and the total number of H, R, K, D, Q, N, and E in X is less than 32. In some embodiments, X of formula (III) is a portion containing 40 to 65 amino acids, and the total number of H, R, K, D, Q, N, and E in X is less than 31. In some embodiments, X of formula (III) is a portion containing 40 to 65 amino acids, and the total number of H, R, K, D, Q, N, and E in X is less than 30. In some embodiments, X of formula (III) is a portion containing 40 to 65 amino acids, and the total number of H, R, K, D, Q, N, and E in X is less than 29. In some embodiments, X of formula (III) is a portion containing 40 to 65 amino acids, and the total number of H, R, K, D, Q, N, and E in X is less than 28. In some embodiments, X of formula (III) is a portion containing 40 to 65 amino acids, and the total number of H, R, K, D, Q, N, and E in X is less than 27. In some embodiments, X of formula (III) is a portion containing 40 to 65 amino acids, and the total number of H, R, K, D, Q, N, and E in X is less than 26. In some embodiments, X of formula (III) is a portion containing 40 to 65 amino acids, and the total number of H, R, K, D, Q, N, and E in X is less than 25. In some embodiments, X of formula (III) is a portion containing 40 to 65 amino acids, and the total number of H, R, K, D, Q, N, and E in X is less than 24. In some embodiments, X of formula (III) is a portion containing 40 to 65 amino acids, and the total number of H, R, K, D, Q, N, and E in X is less than 23. In some embodiments, X of formula (III) is a portion containing 40 to 65 amino acids, and the total number of H, R, K, D, Q, N, and E in X is less than 22.In some embodiments, on pages 31 / 68 of the specification (CN 121079312 A), X of formula (III) is a portion containing 40 to 65 amino acids, and the total number of H, R, K, D, Q, N, and E in X is less than 21. In some embodiments, X of formula (III) is a portion containing 40 to 65 amino acids, and the total number of H, R, K, D, Q, N, and E in X is less than 20.

[0140] In some embodiments, X of formula (III) is a portion containing 40 to 65 amino acids, and the total number of hydrophilic amino acids in X is greater than 10. In some embodiments, X of formula (III) is a portion containing 40 to 65 amino acids, and the total number of hydrophilic amino acids in X is greater than 11. In some embodiments, X of formula (III) is a portion containing 40 to 65 amino acids, and the total number of hydrophilic amino acids in X is greater than 12. In some embodiments, X of formula (III) is a portion containing 40 to 65 amino acids, and the total number of hydrophilic amino acids in X is greater than 13. In some embodiments, X of formula (III) is a portion containing 40 to 65 amino acids, and the total number of hydrophilic amino acids in X is greater than 14. In some embodiments, X of formula (III) is a portion containing 40 to 65 amino acids, and the total number of hydrophilic amino acids in X is greater than 15. In some embodiments, X of formula (III) is a portion containing 40 to 65 amino acids, and the total number of hydrophilic amino acids in X is greater than 16. In some embodiments, X of formula (III) is a portion containing 40 to 65 amino acids, and the total number of hydrophilic amino acids in X is greater than 17. In some embodiments, X of formula (III) is a portion containing 40 to 65 amino acids, and the total number of hydrophilic amino acids in X is greater than 18. In some embodiments, X of formula (III) is a portion containing 40 to 65 amino acids, and the total number of hydrophilic amino acids in X is greater than 19. In some embodiments, X of formula (III) is a portion containing 40 to 65 amino acids, and the total number of hydrophilic amino acids in X is greater than 20. In some embodiments, X of formula (III) is a portion containing 40 to 65 amino acids, and the total number of hydrophilic amino acids in X is greater than 21. In some embodiments, X of formula (III) is a portion containing 40 to 65 amino acids, and the total number of hydrophilic amino acids in X is greater than 22. In some embodiments, X of formula (III) is a portion containing 40 to 65 amino acids, and the total number of hydrophilic amino acids in X is greater than 23. In some embodiments, X of formula (III) is a portion containing 40 to 65 amino acids, and the total number of hydrophilic amino acids in X is greater than 24. In some embodiments, X of formula (III) is a portion containing 40 to 65 amino acids, and the total number of hydrophilic amino acids in X is greater than 25.

[0141] In some embodiments, X of formula (III) is a portion containing 40 to 65 amino acids, and the total number of hydrophobic amino acids in X does not exceed 15. In some embodiments, X of formula (III) is a portion containing 40 to 65 amino acids, and the total number of hydrophobic amino acids in X does not exceed 14. In some embodiments, X of formula (III) is a portion containing 40 to 65 amino acids, and the total number of hydrophobic amino acids in X does not exceed 13. In some embodiments, X of formula (III) is a portion containing 40 to 65 amino acids, and the total number of hydrophobic amino acids in X does not exceed 12. In some embodiments, X of formula (III) is a portion containing 40 to 65 amino acids, and the total number of hydrophobic amino acids in X does not exceed 11. In some embodiments, X of formula (III) is a portion containing 40 to 65 amino acids, and the total number of hydrophobic amino acids in X does not exceed 10. In some embodiments, X of formula (III) is a portion containing 40 to 65 amino acids, and the total number of hydrophobic amino acids in X does not exceed 5.

[0142] In some embodiments, X of formula (III) comprises a sequence having at least 70% identity with any of SEQ ID NO: 23-27. In some embodiments, X of formula (III) comprises a sequence having at least 75% identity with any of SEQ ID NO: 23-27. In some embodiments, X of formula (III) comprises a sequence having at least 80% identity with any of SEQ ID NO: 23-27. In some embodiments, X of formula (III) comprises a sequence having at least 85% identity with any of SEQ ID NO: 23-27. In some embodiments, X of formula (III) comprises a sequence having at least 90% identity with any of SEQ ID NO: 23-27. In some embodiments, X of formula (III) comprises a sequence having at least 95% identity with any of SEQ ID NO: 23-27. In some embodiments, X of formula (III) comprises a sequence having at least 96%, at least 97%, at least 98%, or at least 99% identity with any of SEQ ID NO: 23-27. In some embodiments, X of formula (III) comprises a sequence selected from any of SEQ ID NO: 23-27. In some embodiments, X of formula (III) is a sequence selected from any of SEQ ID NO: 23-27.

[0143] In some embodiments, Y in formula (III) is a portion comprising a sequence having at least 70% identity with SEQ ID NO: 2. In some embodiments, Y in formula (III) is a portion comprising a sequence having at least 75% identity with SEQ ID NO: 2. In some embodiments, Y in formula (III) is a portion comprising a sequence having at least 80% identity with SEQ ID NO: 2. In some embodiments, Y in formula (III) is a portion comprising a sequence having at least 85% identity with SEQ ID NO: 2. In some embodiments, Y in formula (III) is a portion comprising a sequence having at least 90% identity with SEQ ID NO: 2. In some embodiments, Y in formula (III) is a portion comprising a sequence having at least 95% identity with SEQ ID NO: 2. In some embodiments, Y in formula (III) is a portion comprising a sequence of SEQ ID NO: 2. In some embodiments, Y in formula (III) is a portion of the sequence SEQ ID NO: 2.

[0144] In some embodiments, Y in formula (III) is a hydrophobic portion, wherein at least 50% of the amino acids in Y are selected from I, V, L, F, C, M, and A. In some embodiments, Y in formula (III) is a hydrophobic portion, wherein at least 55% of the amino acids in Y are selected from I, V, L, F, C, M, and A. In some embodiments, Y in formula (III) is a hydrophobic portion, wherein at least 60% of the amino acids in Y are selected from I, V, L, F, C, M, and A. In some embodiments, Y in formula (III) is a hydrophobic portion, wherein at least 65% of the amino acids in Y are selected from I, V, L, F, C, M, and A. In some embodiments, Y in formula (III) is a hydrophobic portion, wherein at least 70% of the amino acids in Y are selected from I, V, L, F, C, M, and A. In some embodiments, Y in formula (III) is a hydrophobic moiety, and at least 75% of the amino acids in Y are selected from I, V, L, F, C, M, and A. In some embodiments, Y in formula (III) is a hydrophobic moiety, and at least 80% of the amino acids in Y are selected from I, V, L, F, C, M, and A. In some embodiments, Y in formula (III) is a hydrophobic moiety, and at least 85% of the amino acids in Y are selected from I, V, L, F, C, M, and A. In some embodiments, Y in formula (III) is a hydrophobic moiety, and at least 90% of the amino acids in Y are selected from I, V, L, F, C, M, and A.

[0145] In some embodiments, the artificial polypeptide of formula (III) comprises a sequence having at least 70% identity with any of SEQ ID NO: 49-53. In some embodiments, the artificial polypeptide of formula (III) comprises a sequence having at least 75% identity with any of SEQ ID NO: 49-53. In some embodiments, the artificial polypeptide of formula (III) comprises a sequence having at least 80% identity with any of SEQ ID NO: 49-53. In some embodiments, the artificial polypeptide of formula (III) comprises a sequence having at least 85% identity with any of SEQ ID NO: 49-53. In some embodiments, the artificial polypeptide of formula (III) comprises a sequence having at least 90% identity with any of SEQ ID NO: 49-53. In some embodiments, the artificial polypeptide of formula (III) comprises a sequence having at least 95% identity with any of SEQ ID NO: 49-53. In some embodiments, the artificial polypeptide of formula (III) comprises a sequence having at least 96%, at least 97%, at least 98%, or at least 99% identity with any of SEQ ID NO: 49-53. In some embodiments, the artificial polypeptide of formula (III) comprises a sequence selected from any of SEQ ID NO: 49-53. In some embodiments, the artificial polypeptide of formula (III) is a sequence selected from any of SEQ ID NO: 49-53.

[0146] In another aspect, a method is provided for treating or preventing allergic conjunctivitis in a subject in need, comprising administering to the subject an effective amount of an artificial polypeptide of formula (IV): X-Y (IV), wherein X is a portion comprising 40 to 65 amino acids, at least 50% of which are selected from H, R, K, D, Q, N, and E; and Y is a portion comprising a sequence having at least 80% identity with SEQ ID NO: 2, (Specification 33 / 68 pages 54 CN 121079312 A) wherein X comprises a sequence having at most 90% identity with SEQ ID NO: 1.

[0147] In some embodiments, X of formula (IV) is a hydrophilic portion, wherein at least 50% is selected from H, R, K, D, Q, N, and E. In some embodiments, X of formula (IV) may be a hydrophilic portion, wherein at least 55% is selected from R, K, N, D, Q, E, and H. In some embodiments, X in formula (IV) may be a hydrophilic portion, wherein at least 60% is selected from R, K, N, D, Q, E, and H. In some embodiments, X in formula (IV) may be a hydrophilic portion, wherein at least 65% is selected from R, K, N, D, Q, E, and H.In some embodiments, X of formula (IV) may be a hydrophilic moiety, wherein at least 70% is selected from R, K, N, D, Q, E, and H. In some embodiments, X of formula (IV) may be a hydrophilic moiety, wherein at least 75% is selected from R, K, N, D, Q, E, and H. In some embodiments, X of formula (IV) may be a hydrophilic moiety, wherein at least 80% is selected from R, K, N, D, Q, E, and H. In some embodiments, X of formula (IV) may be a hydrophilic moiety, wherein at least 85% is selected from R, K, N, D, Q, E, and H. In some embodiments, X of formula (IV) may be a hydrophilic moiety, wherein at least 90% is selected from R, K, N, D, Q, E, and H.

[0148] In some embodiments, X of formula (IV) comprises 40 to 65 amino acids, and the total number of hydrophilic amino acids in X is greater than 10. In some embodiments, X of formula (IV) comprises 40 to 65 amino acids, and the total number of hydrophilic amino acids in X is greater than 15. In some embodiments, X of formula (IV) comprises 40 to 65 amino acids, and the total number of hydrophilic amino acids in X is greater than 20. In some embodiments, X of formula (IV) comprises 40 to 65 amino acids, and the total number of hydrophilic amino acids in X is greater than 25. In some embodiments, X of formula (IV) comprises 40 to 65 amino acids, and the total number of hydrophilic amino acids in X is greater than 30. In some embodiments, X of formula (IV) comprises 40 to 65 amino acids, and the total number of hydrophilic amino acids in X is greater than 35.

[0149] In some embodiments, X of formula (IV) comprises a sequence having up to 50% identity with SEQ ID NO: 1. In some embodiments, X of formula (IV) comprises a sequence having up to 55% identity with SEQ ID NO: 1. In some embodiments, X of formula (IV) comprises a sequence having at most 60% identity with SEQ ID NO: 1. In some embodiments, X of formula (IV) comprises a sequence having at most 65% identity with SEQ ID NO: 1. In some embodiments, X of formula (IV) comprises a sequence having at most 70% identity with SEQ ID NO: 1. In some embodiments, X of formula (IV) comprises a sequence having at most 75% identity with SEQ ID NO: 1. In some embodiments, X of formula (IV) comprises a sequence having at most 80% identity with SEQ ID NO: 1. In some embodiments, X of formula (IV) comprises a sequence having at most 85% identity with SEQ ID NO: 1. In some embodiments, X of formula (IV) comprises a sequence having at most 90% identity with SEQ ID NO: 1.

[0150] In some embodiments, Y of formula (IV) is a portion comprising a sequence having at least 70% identity with SEQ ID NO: 2. In some embodiments, Y of formula (IV) is a portion comprising a sequence having at least 75% identity with SEQ ID NO: 2. In some embodiments, Y of formula (IV) is a portion comprising a sequence having at least 80% identity with SEQ ID NO: 2. In some embodiments, Y of formula (IV) is a portion comprising a sequence having at least 85% identity with SEQ ID NO: 2. In some embodiments, Y of formula (IV) is a portion comprising a sequence having at least 90% identity with SEQ ID NO: 2. In some embodiments, Y of formula (IV) is a portion comprising a sequence having at least 95% identity with SEQ ID NO: 2. In some embodiments, Y of formula (IV) is a portion comprising a sequence of SEQ ID NO: 2. In some embodiments, Y of formula (IV) is a portion comprising the sequence of SEQ ID NO: 2. In some embodiments, Y in formula (IV) is a portion of the sequence SEQ ID NO: 2.

[0151] In some embodiments, Y in formula (IV) is a hydrophobic portion, and at least 50% of the amino acids in Y are selected from I, V, L, F, C, M, and A. In some embodiments, Y in formula (IV) is a hydrophobic portion, and at least 55% of the amino acids in Y are selected from I, V, L, F, C, M, and A. In some embodiments, Y in formula (IV) is a hydrophobic portion, and at least 60% of the amino acids in Y are selected from I, V, L, F, C, M, and A. In some embodiments, Y in formula (IV) is a hydrophobic portion, and at least 65% of the amino acids in Y are selected from I, V, L, F, C, M, and A. In some embodiments, Y in formula (IV) is a hydrophobic portion, and at least 70% of the amino acids in Y are selected from I, V, L, F, C, M, and A. In some embodiments, Y in formula (IV) is a hydrophobic moiety, and at least 75% of the amino acids in Y are selected from I, V, L, F, C, M, and A. In some embodiments, Y in formula (IV) is a hydrophobic moiety, and at least 80% of the amino acids in Y are selected from I, V, L, F, C, M, and A. In some embodiments, Y in formula (IV) is a hydrophobic moiety, and at least 85% of the amino acids in Y are selected from I, V, L, F, C, M, and A. In some embodiments, Y in formula (IV) is a hydrophobic moiety, and at least 90% of the amino acids in Y are selected from I, V, L, F, C, M, and A.

[0152] In some embodiments, X of formula (IV) comprises a sequence having at least 70% identity with any one of SEQ ID NO. 19-22 and 76-79. In some embodiments, X of formula (IV) comprises a sequence having at least 75% identity with any one of SEQ ID NO. 19-22 and 76-79. In some embodiments, X of formula (IV) comprises a sequence having at least 80% identity with any one of SEQ ID NO. 19-22 and 76-79. In some embodiments, X of formula (IV) comprises a sequence having at least 85% identity with any one of SEQ ID NO. 19-22 and 76-79. In some embodiments, X of formula (IV) comprises a sequence having at least 90% identity with any one of SEQ ID NO. 19-22 and 76-79. In some embodiments, X of formula (IV) comprises a sequence having at least 95% identity with any one of SEQ ID NO. 19-22 and 76-79. In some embodiments, X of formula (IV) comprises a sequence having at least 96%, at least 97%, at least 98%, or at least 99% identity with any one of SEQ ID NO. 19-22 and 76-79. In some embodiments, X of formula (IV) comprises a sequence selected from any one of SEQ ID NO. 19-22 and 76-79. In some embodiments, X of formula (IV) is a sequence selected from any one of SEQ ID NO. 19-22 and 76-79.

[0153] In some embodiments, the artificial polypeptide of formula (IV) comprises a sequence having at least 70% identity with any one of SEQ ID NO: 45-48 and 86-89. In some embodiments, the artificial polypeptide of formula (IV) comprises a sequence having at least 75% identity with any one of SEQ ID NO: 45-48 and 86-89. In some embodiments, the artificial polypeptide of formula (IV) comprises a sequence having at least 80% identity with any one of SEQ ID NO: 45-48 and 86-89. In some embodiments, the artificial polypeptide of formula (IV) comprises a sequence having at least 85% identity with any one of SEQ ID NO: 45-48 and 86-89. In some embodiments, the artificial polypeptide of formula (IV) comprises a sequence having at least 90% identity with any one of SEQ ID NO: 45-48 and 86-89. In some embodiments, the artificial polypeptide of formula (IV) comprises a sequence having at least 95% identity with any one of SEQ ID NO: 45-48 and 86-89.In some embodiments, the artificial polypeptide of formula (IV) comprises a sequence having at least 96%, at least 97%, at least 98%, or at least 99% identity with any of SEQ ID NO: 45-48 and 86-89. In some embodiments, the artificial polypeptide of formula (IV) comprises a sequence selected from any of SEQ ID NO: 45-48 and 86-89. In some embodiments, the artificial polypeptide of formula (IV) is a sequence selected from any of SEQ ID NO: 45-48 and 86-89.

[0154] In another aspect, a method for treating or preventing allergic conjunctivitis in a subject in need is provided, comprising administering to the subject an effective amount of the artificial polypeptide of formula (V): X-Y (V), wherein X is a portion comprising a sequence having at least 80% identity with SEQ ID NO: 1, and Y is a portion comprising 10 to 30 amino acids, wherein Y comprises a sequence having at least 10 consecutive AAs of SEQ ID NO: 2.

[0155] In some embodiments, Y of formula (V) comprises 10 to 25 amino acids. In some embodiments, Y comprises 10 to 20 amino acids. In some embodiments, Y comprises 10 to 15 amino acids. In some embodiments, Y comprises 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 amino acids. Specification 35 / 68 pages 56 CN 121079312 A

[0156] In some embodiments, X of formula (V) may be a portion comprising a sequence having at least 80% identity with SEQ ID NO: 1. In some embodiments, X is a portion comprising a sequence having at least 85% identity with SEQ ID NO: 1. In some embodiments, X is a portion comprising a sequence having at least 90% identity with SEQ ID NO: 1. In some embodiments, X is a portion comprising a sequence having at least 95% identity with SEQ ID NO: 1. In some embodiments, X is a portion comprising a sequence having at least 96%, at least 97%, at least 98%, or at least 99% identity with SEQ ID NO: 1. In some embodiments, X is a portion comprising the sequence of SEQ ID NO: 1. In some embodiments, X is a portion that is precisely the sequence of SEQ ID NO: 1.

[0157] In some embodiments of the artificial polypeptide of formula (V), at least 50% of the amino acids in X are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 55% of the amino acids in X are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 60% of the amino acids in X are selected from R, K, N, D, Q, E, and H.In some embodiments, at least 65% of the amino acids in X are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 70% of the amino acids in X are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 75% of the amino acids in X are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 80% of the amino acids in X are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 85% of the amino acids in X are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 90% of the amino acids in X are selected from R, K, N, D, Q, E, and H.

[0158] In some embodiments of the artificial polypeptide of formula (V), X comprises a sequence having at least 70% identity with SEQ ID NO: 96. In some embodiments of the artificial polypeptide of formula (V), X comprises a sequence having at least 75% identity with SEQ ID NO: 96. In some embodiments of the artificial polypeptide of formula (V), X comprises a sequence having at least 80% identity with SEQ ID NO: 96. In some embodiments, X comprises a sequence having at least 85% identity with SEQ ID NO: 96. In some embodiments, X comprises a sequence having at least 90% identity with SEQ ID NO: 96. In some embodiments, X comprises a sequence having at least 95% identity with SEQ ID NO: 96. In some embodiments, X comprises a sequence having at least 96%, at least 97%, at least 98%, or at least 99% identity with SEQ ID NO: 96. In some embodiments, X comprises the sequence of SEQ ID NO: 96. In some embodiments, X is the sequence of SEQ ID NO: 96.

[0159] In some embodiments of the artificial polypeptide of formula (V), Y comprises a sequence having at most 50% identity with SEQ ID NO: 2. In some embodiments, Y comprises a sequence having at most 55% identity with SEQ ID NO: 2. In some embodiments, Y comprises a sequence having up to 60% identity with SEQ ID NO: 2. In some embodiments, Y comprises a sequence having up to 65% identity with SEQ ID NO: 2. In some embodiments, Y comprises a sequence having up to 70% identity with SEQ ID NO: 2. In some embodiments, Y comprises a sequence having up to 75% identity with SEQ ID NO: 2. In some embodiments, Y comprises a sequence having up to 80% identity with SEQ ID NO: 2. In some embodiments, Y comprises a sequence having up to 85% identity with SEQ ID NO: 2. In some embodiments, Y comprises a sequence having up to 90% identity with SEQ ID NO: 2.

[0160] In some embodiments of the artificial polypeptide of formula (V), Y comprises a sequence having at least 70% identity with any of SEQ ID NO: 97-103. In some embodiments of the artificial polypeptide of formula (V), Y comprises a sequence having at least 75% identity with any of SEQ ID NO: 97-103. In some embodiments of the artificial polypeptide of formula (V), Y comprises a sequence having at least 80% identity with any of SEQ ID NO: 97-103. In some embodiments, Y comprises a sequence having at least 85% identity with any of SEQ ID NO: 97-103. In some embodiments, Y comprises a sequence having at least 90% identity with any of SEQ ID NO: 97-103. In some embodiments, Y comprises a sequence having at least 95% identity with any of SEQ ID NO: 97-103. In some embodiments, Y comprises a sequence having at least 96%, at least 97%, at least 98%, or at least 99% identity with any of SEQ ID NO: 97-103. In some embodiments, Y comprises a sequence selected from SEQ ID NO: 97-103. In some embodiments, Y is any of the sequences selected from SEQ ID NO: 97-103.

[0161] In some embodiments, the artificial polypeptide of formula (V) comprises a sequence having at least 70% identity with any of SEQ ID NO: 53-56 and 104-110. In some embodiments, the artificial polypeptide of formula (V) comprises a sequence having at least 75% identity with any of SEQ ID NO: 53-56 and 104-110. In some embodiments, the artificial polypeptide of formula (V) comprises a sequence having at least 80% identity with any of SEQ ID NO: 53-56 and 104-110. In some embodiments, the artificial polypeptide of formula (V) comprises a sequence having at least 85% identity with any one of SEQ ID NO: 53-56 and 104-110. In some embodiments, the artificial polypeptide of formula (V) comprises a sequence having at least 90% identity with any one of SEQ ID NO: 53-56 and 104-110. In some embodiments, the artificial polypeptide of formula (V) comprises a sequence having at least 95% identity with any one of SEQ ID NO: 53-56 and 104-110.In some embodiments, the artificial polypeptide of formula (V) comprises a sequence having at least 96%, at least 97%, at least 98%, or at least 99% identity with any one of SEQ ID NO: 53-56 and 104-110. In some embodiments, the artificial polypeptide of formula (V) is a sequence selected from any one of SEQ ID NO: 53-56 and 104-110.

[0162] In another aspect, a method for treating or preventing allergic conjunctivitis in a subject in need is provided, comprising administering to the subject an effective amount of an artificial polypeptide of formula (VI): X-Y (VI), wherein X is a portion comprising a mutant of the sequence SEQ ID NO: 1, characterized in that the mutant mutates at least 1, 2, 3, 4, 5, 6, 7, 8, or 9 Ds in SEQ ID NO: 1 to S, and / or mutates at least 1, 2, 3, 4, 5, or 6 Es in SEQ ID NO: 1 to T; and Y is a portion comprising a mutant of the sequence SEQ ID NO: 2, characterized in that the mutant mutates at least 1, 2, 3, 4, or 5 Cs in SEQ ID NO: 2 to A.

[0163] In some embodiments, X of formula (VI) comprises a sequence having at least 70% identity with SEQ ID NO: 1. In some embodiments, X of formula (VI) comprises a sequence having at least 75% identity with SEQ ID NO: 1. In some embodiments, X of formula (VI) comprises a sequence having at least 80% identity with SEQ ID NO: 1. In some embodiments, X of formula (VI) comprises a sequence having at least 85% identity with SEQ ID NO: 1. In some embodiments, X of formula (VI) comprises a sequence having at least 90% identity with SEQ ID NO: 1. In some embodiments, X of formula (VI) comprises a sequence having at least 95% identity with SEQ ID NO: 1. In some embodiments, X of formula (VI) comprises a sequence having at most 95% identity with SEQ ID NO: 1. In some embodiments, X of formula (VI) comprises a sequence having at most 90% identity with SEQ ID NO: 1. In some embodiments, X of formula (VI) comprises a sequence having at most 85% identity with SEQ ID NO: 1. In some embodiments, X of formula (VI) comprises a sequence having at most 80% identity with SEQ ID NO: 1. In some implementations, X of formula (VI) contains a sequence that has up to 75% identity with SEQ ID NO: 1.

[0164] In some embodiments, Y of formula (VI) is a portion comprising a sequence having at least 70% identity with SEQ ID NO: 2. In some embodiments, Y of formula (VI) is a portion comprising a sequence having at least 75% identity with SEQ ID NO: 2. In some embodiments, Y of formula (VI) is a portion comprising a sequence having at least 80% identity with SEQ ID NO: 2. In some embodiments, Y of formula (VI) is a portion comprising a sequence having at least 85% identity with SEQ ID NO: 2. In some embodiments, Y of formula (VI) is a portion comprising a sequence having at least 90% identity with SEQ ID NO: 2. In some embodiments, Y of formula (VI) is a portion comprising a sequence having at least 95% identity with SEQ ID NO: 2. In some embodiments, Y of formula (VI) comprises a sequence having at most 95% identity with SEQ ID NO: 2. In some embodiments, Y of formula (VI) comprises a sequence having at most 90% identity with SEQ ID NO: 2. In some embodiments, as described on pages 37 / 68 of CN 121079312 A, the Y of formula (VI) contains a sequence having at most 85% identity with SEQ ID NO: 2. In some embodiments, the Y of formula (VI) contains a sequence having at most 80% identity with SEQ ID NO: 2. In some embodiments, the Y of formula (VI) contains a sequence having at most 75% identity with SEQ ID NO: 2.

[0165] In some embodiments, the Y of formula (VI) is a hydrophobic portion, and at least 50% of the amino acids in Y are selected from I, V, L, F, C, M, and A. In some embodiments, the Y of formula (VI) is a hydrophobic portion, and at least 55% of the amino acids in Y are selected from I, V, L, F, C, M, and A. In some embodiments, the Y of formula (VI) is a hydrophobic portion, and at least 60% of the amino acids in Y are selected from I, V, L, F, C, M, and A. In some embodiments, Y in formula (VI) is a hydrophobic moiety, and at least 65% of the amino acids in Y are selected from I, V, L, F, C, M, and A. In some embodiments, Y in formula (VI) is a hydrophobic moiety, and at least 70% of the amino acids in Y are selected from I, V, L, F, C, M, and A. In some embodiments, Y in formula (VI) is a hydrophobic moiety, and at least 75% of the amino acids in Y are selected from I, V, L, F, C, M, and A. In some embodiments, Y in formula (VI) is a hydrophobic moiety, and at least 80% of the amino acids in Y are selected from I, V, L, F, C, M, and A. In some embodiments, Y in formula (VI) is a hydrophobic moiety, and at least 85% of the amino acids in Y are selected from I, V, L, F, C, M, and A.In some embodiments, Y of formula (VI) is a hydrophobic portion, wherein at least 90% of the amino acids in Y are selected from I, V, L, F, C, M, and A.

[0166] In some embodiments, X of formula (VI) is a portion comprising 40 to 65 amino acids, and the total number of R, K, T, A, N, Q, D, E, S, and G in X is greater than 30. In some embodiments, X of formula (VI) is a portion comprising 40 to 65 amino acids, and the total number of R, K, T, A, N, Q, D, E, S, and G in X is 31, 32, 33, 34, 35, 36, 37, 38, 39, or 40. In some embodiments, X of formula (VI) is a portion comprising 40 to 65 amino acids, and the total number of W, Y, F, M, L, I, and V in X does not exceed 20. In some embodiments, X of formula (VI) is a portion containing 40 to 65 amino acids, and the total number of W, Y, F, M, L, I, and V in X is 19, 18, 17, 16, 15, or 14.

[0167] In some embodiments, Y of formula (VI) is a portion containing 10 to 50 amino acids, and the total number of R, K, T, A, N, Q, D, E, S, and G in Y is greater than 10. In some embodiments, Y of formula (VI) is a portion containing 10 to 50 amino acids, and the total number of R, K, T, A, N, Q, D, E, S, and G in Y is 11, 12, 13, 14, or 15. In some embodiments, Y of formula (VI) is a portion containing 10 to 50 amino acids, and the total number of W, Y, F, M, L, I, and V in X does not exceed 20. In some embodiments, Y of formula (VI) is a portion comprising 10 to 50 amino acids, and the total number of W, Y, F, M, L, I, and V in Y is 19, 18, 17, 16, 15, or 14.

[0168] In some embodiments, X of formula (VI) comprises a sequence having at least 70% identity with any of SEQ ID NO: 80-83. In some embodiments, X of formula (VI) comprises a sequence having at least 75% identity with any of SEQ ID NO: 80-83. In some embodiments, X of formula (VI) comprises a sequence having at least 80% identity with any of SEQ ID NO: 80-83. In some embodiments, X of formula (VI) comprises a sequence having at least 85% identity with any of SEQ ID NO: 80-83. In some embodiments, X of formula (VI) comprises a sequence having at least 90% identity with any of SEQ ID NO: 80-83. In some embodiments, X of formula (VI) comprises a sequence that has at least 95% identity with any one of SEQ ID NO: 80-83.In some embodiments, X of formula (VI) comprises a sequence having at least 96%, at least 97%, at least 98%, or at least 99% identity with any of SEQ ID NO: 80-83. In some embodiments, X of formula (VI) comprises a sequence selected from any of SEQ ID NO: 80-83. In some embodiments, X of formula (VI) is a sequence selected from any of SEQ ID NO: 80-83.

[0169] In some embodiments, Y of formula (VI) comprises a sequence having at least 70% identity with SEQ ID NO: 3. In some embodiments, Y of formula (VI) comprises a sequence having at least 75% identity with SEQ ID NO: 3. In some embodiments, Y of formula (VI) comprises a sequence having at least 80% identity with SEQ ID NO: 3. In some embodiments, Y of formula (VI) comprises a sequence having at least 85% identity with SEQ ID NO: 3. In some embodiments, Y of formula (VI) comprises a sequence having at least 90% identity with SEQ ID NO: 3. In some embodiments, Y of formula (VI) comprises a sequence having at least 95% identity with SEQ ID NO: 3. In some embodiments, Y of formula (VI) comprises a sequence having at least 96%, at least 97%, at least 98%, or at least 99% identity with SEQ ID NO: 3. In some embodiments, Y of formula (VI) comprises the sequence of SEQ ID NO: 3. In some embodiments, Y of formula (VI) is the sequence of SEQ ID NO: 3.

[0170] In some embodiments, the artificial polypeptide of formula (VI) comprises a sequence having at least 70% identity with any one of SEQ ID NO: 90-93. In some embodiments, the artificial polypeptide of formula (VI) comprises a sequence having at least 75% identity with any one of SEQ ID NO: 90-93. In some embodiments, the artificial polypeptide of formula (VI) comprises a sequence having at least 80% identity with any one of SEQ ID NO: 90-93. In some embodiments, the artificial polypeptide of formula (VI) comprises a sequence having at least 85% identity with any one of SEQ ID NO: 90-93. In some embodiments, the artificial polypeptide of formula (VI) comprises a sequence having at least 90% identity with any one of SEQ ID NO: 90-93. In some embodiments, the artificial polypeptide of formula (VI) comprises a sequence having at least 95% identity with any one of SEQ ID NO: 90-93.In some embodiments, the artificial polypeptide of formula (VI) comprises a sequence having at least 96%, at least 97%, at least 98%, or at least 99% identity with any of SEQ ID NO: 90-93. In some embodiments, the artificial polypeptide of formula (VI) comprises a sequence selected from any of SEQ ID NO: 90-93. In some embodiments, the artificial polypeptide of formula (VI) is a sequence selected from any of SEQ ID NO: 90-93.

[0171] In one aspect, a method for treating or preventing allergic conjunctivitis in a subject in need is provided, comprising administering to the subject an effective amount of the artificial polypeptide of formula (VII): X-Y (VII), wherein X is a portion comprising a mutant of the sequence SEQ ID NO: 1, characterized in that the mutant has at least 1, 2, 3, 4, or 5 amino acid insertions relative to SEQ ID NO: 1, and Y is a portion comprising 10 to 30 amino acids, wherein Y comprises a sequence having at least 15 consecutive AAs of SEQ ID NO: 2.

[0172] In some embodiments, X is a portion comprising a mutant of the sequence SEQ ID NO: 1, characterized in that the mutant has at least 1, 2, 3, 4, or 5 amino acid insertions relative to SEQ ID NO: 1. In some embodiments, X is a portion comprising a mutant of the sequence SEQ ID NO: 1, characterized in that the mutant has at least 1 amino acid insertion relative to SEQ ID NO: 1. In some embodiments, X is a portion comprising a mutant of the sequence SEQ ID NO: 1, characterized in that the mutant has 1 amino acid insertion relative to SEQ ID NO: 1. In some embodiments, X is a portion comprising a mutant of the sequence SEQ ID NO: 1, characterized in that the mutant has at least 2 amino acid insertions relative to SEQ ID NO: 1. In some embodiments, X is a portion comprising a mutant of the sequence SEQ ID NO: 1, characterized in that the mutant has 2 amino acid insertions relative to SEQ ID NO: 1. In some embodiments, X is a portion comprising a mutant of the sequence SEQ ID NO: 1, characterized in that the mutant has at least 3 amino acid insertions relative to SEQ ID NO: 1. In some embodiments, X is a portion comprising a mutant of the sequence SEQ ID NO: 1, characterized in that the mutant has a 3-amino acid insertion relative to SEQ ID NO: 1. In some embodiments, X is a portion comprising a mutant of the sequence SEQ ID NO: 1, characterized in that the mutant has at least a 4-amino acid insertion relative to SEQ ID NO: 1.In some embodiments, X is a portion comprising a mutant of the sequence SEQ ID NO: 1, characterized in that the mutant has a 4-amino acid insertion relative to SEQ ID NO: 1. In some embodiments, X is a portion comprising a mutant of the sequence SEQ ID NO: 1, characterized in that the mutant has at least a 5-amino acid insertion relative to SEQ ID NO: 1. In some embodiments, X is a portion comprising a mutant of the sequence SEQ ID NO: 1, characterized in that the mutant has a 5-amino acid insertion relative to SEQ ID NO: 1. Specification 39 / 68 pages 60 CN 121079312 A

[0173] In some embodiments, at least 20% of the amino acids in X of the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 25% of the amino acids in X of the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 30% of the amino acids in X of the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 35% of the amino acids in X of the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 40% of the amino acids in X of the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 45% of the amino acids in X of the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 50% of the amino acids in X of the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 55% of the amino acids in X of the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 60% of the amino acids in X of the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 65% of the amino acids in X of the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 70% of the amino acids in X of the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, up to 75% of the amino acids in X of the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, up to 80% of the amino acids in X of the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, up to 85% of the amino acids in X of the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, up to 90% of the amino acids in X of the mutant are selected from R, K, N, D, Q, E, and H.

[0174] In some embodiments, Y is a portion comprising 10 to 30 amino acids.In some embodiments, Y is a portion containing 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 amino acids. In some embodiments, Y is a portion containing 11 to 29 amino acids. In some embodiments, Y is a portion containing 12 to 28 amino acids. In some embodiments, Y is a portion containing 13 to 27 amino acids. In some embodiments, Y is a portion containing 14 to 26 amino acids. In some embodiments, Y is a portion containing 15 to 25 amino acids. In some embodiments, Y contains 15 to 25 amino acids. In some embodiments, Y contains 18 to 25 amino acids. In some embodiments, Y contains 20 to 25 amino acids.

[0175] In some embodiments, Y comprises a sequence of at least 15 consecutive AAs having SEQ ID NO: 2. In some embodiments, Y comprises a sequence of 15 consecutive AAs having SEQ ID NO: 2. In some embodiments, Y comprises a sequence of at least 16 consecutive AAs having SEQ ID NO: 2. In some embodiments, Y comprises a sequence of 16 consecutive AAs having SEQ ID NO: 2. In some embodiments, Y comprises a sequence of at least 17 consecutive AAs having SEQ ID NO: 2. In some embodiments, Y comprises a sequence of 17 consecutive AAs having SEQ ID NO: 2. In some embodiments, Y comprises a sequence of at least 18 consecutive AAs having SEQ ID NO: 2. In some embodiments, Y comprises a sequence of 18 consecutive AAs having SEQ ID NO: 2. In some embodiments, Y comprises a sequence of at least 19 consecutive AAs having SEQ ID NO: 2. In some embodiments, Y comprises a sequence of 19 consecutive AAs having SEQ ID NO: 2. In some embodiments, Y comprises a sequence of at least 20 consecutive AAs having SEQ ID NO: 2. In some embodiments, Y comprises a sequence of 20 consecutive AAs having SEQ ID NO: 2. In some embodiments, Y comprises a sequence of at least 21 consecutive AAs having SEQ ID NO: 2. In some embodiments, Y comprises a sequence of 21 consecutive AAs having SEQ ID NO: 2. In some embodiments, Y comprises a sequence of at least 22 consecutive AAs having SEQ ID NO: 2.In some embodiments, Y comprises a sequence of 22 consecutive AAs having SEQ ID NO: 2. In some embodiments, Y comprises a sequence of at least 23 consecutive AAs having SEQ ID NO: 2. In some embodiments, Y comprises a sequence of 23 consecutive AAs having SEQ ID NO: 2. In some embodiments, Y comprises a sequence of at least 24 consecutive AAs having SEQ ID NO: 2. In some embodiments, Y comprises a sequence of 24 consecutive AAs having SEQ ID NO: 2. In some embodiments, Y comprises a sequence of at least 25 consecutive AAs having SEQ ID NO: 2. In some embodiments, Y comprises a sequence of 25 consecutive AAs having SEQ ID NO: 2. (See specification page 40 / 68, page 61, CN 121079312 A).

[0176] In some embodiments, Y is a portion comprising a mutant of the sequence SEQ ID NO: 2, characterized in that the mutant has a truncation of at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acids relative to SEQ ID NO: 2. In some embodiments, the truncation of at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acids is located at the C-terminus of Y. In some embodiments, Y is a portion comprising a mutant of the sequence SEQ ID NO: 2, characterized in that the mutant has a truncation of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acids relative to SEQ ID NO: 2. In some embodiments, amino acids 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 are truncated at the C-terminus of Y.

[0177] In some embodiments, the total number of E or D in X is at least 8. In some embodiments, the total number of E or D in X is 8. In some embodiments, the total number of E or D in X is at least 9. In some embodiments, the total number of E or D in X is 9. In some embodiments, the total number of E or D in X is at least 10. In some embodiments, the total number of E or D in X is 10. In some embodiments, the total number of E or D in X is at least 11. In some embodiments, the total number of E or D in X is 11. In some embodiments, the total number of E or D in X is at least 12. In some embodiments, the total number of E or D in X is 12. In some embodiments, the total number of E or D in X is at most 15. In some implementations, the total number of E or D in X is 15.In some embodiments, the total number of E or D in X is at most 14. In some embodiments, the total number of E or D in X is 14. In some embodiments, the total number of E or D in X is at most 13. In some embodiments, the total number of E or D in X is 13. In some embodiments, the total number of E or D in X is at most 12. In some embodiments, the total number of E or D in X is 12. In some embodiments, the total number of E or D in X is at most 11. In some embodiments, the total number of E or D in X is 11. In some embodiments, the total number of E or D in X is at most 10. In some embodiments, the total number of E or D in X is 10.

[0178] In some embodiments, X of formula (VII) is a portion containing 40 to 65 amino acids, and the total number of R, K, T, A, N, Q, D, E, S, and G in X is greater than 30. In some embodiments, X of formula (VII) is a portion containing 40 to 65 amino acids, and the total number of R, K, T, A, N, Q, D, E, S, and G in X is 31, 32, 33, 34, 35, 36, 37, 38, 39, or 40. In some embodiments, X of formula (VII) is a portion containing 40 to 65 amino acids, and the total number of W, Y, F, M, L, I, and V in X does not exceed 20. In some embodiments, X of formula (VII) is a portion containing 40 to 65 amino acids, and the total number of W, Y, F, M, L, I, and V in X is 19, 18, 17, 16, 15, or 14.

[0179] In some embodiments, 40-65% of the amino acids in Y are selected from I, V, L, F, C, M, and A. In some embodiments, at least 40% of the amino acids in Y are selected from I, V, L, F, C, M, and A. In some embodiments, at least 45% of the amino acids in Y are selected from I, V, L, F, C, M, and A. In some embodiments, at least 50% of the amino acids in Y are selected from I, V, L, F, C, M, and A. In some embodiments, at least 55% of the amino acids in Y are selected from I, V, L, F, C, M, and A. In some embodiments, at least 60% of the amino acids in Y are selected from I, V, L, F, C, M, and A. In some embodiments, up to 65% of the amino acids in Y are selected from I, V, L, F, C, M, and A. In some embodiments, up to 60% of the amino acids in Y are selected from I, V, L, F, C, M, and A. In some embodiments, up to 55% of the amino acids in Y are selected from I, V, L, F, C, M, and A. In some embodiments, up to 50% of the amino acids in Y are selected from I, V, L, F, C, M, and A. In some embodiments, up to 45% of the amino acids in Y are selected from I, V, L, F, C, M, and A.

[0180] In some embodiments, the total number of R, K, T, A, N, Q, D, E, S, and G in Y does not exceed 10.In some embodiments, the total number of R, K, T, A, N, Q, D, E, S, and G in Y is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10. In some embodiments, the total number of W, Y, F, M, L, I, and V in Y is no more than 15. In some embodiments, the total number of W, Y, F, M, L, I, and V in Y is 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15.

[0181] In some embodiments, X of formula (VII) contains a sequence having at least 70% identity with SEQ ID NO: 96. In some embodiments, X of formula (VII) contains a sequence having at least 75% identity with SEQ ID NO: 96. In some embodiments, X of formula (VII) contains a sequence having at least 80% identity with SEQ ID NO: 96. In some embodiments, X of formula (VII) comprises a sequence having at least 85% identity with SEQ ID NO: 96. In some embodiments, X of formula (VII) comprises a sequence having at least 90% identity with SEQ ID NO: 96. In some embodiments, X of formula (VII) comprises a sequence having at least 95% identity with SEQ ID NO: 96. In some embodiments, X of formula (VII) comprises a sequence having at least 96%, at least 97%, at least 98%, or at least 99% identity with SEQ ID NO: 96. In some embodiments, X of formula (VII) comprises a sequence of SEQ ID NO: 96. In some embodiments, X of formula (VII) is a sequence of SEQ ID NO: 96.

[0182] In some embodiments, Y of formula (VII) comprises a sequence having at least 70% identity with any one of SEQ ID NO: 97-103. In some embodiments, Y of formula (VII) comprises a sequence having at least 75% identity with any one of SEQ ID NO: 97-103. In some embodiments, Y of formula (VII) comprises a sequence having at least 80% identity with any of SEQ ID NO: 97-103. In some embodiments, Y of formula (VII) comprises a sequence having at least 85% identity with any of SEQ ID NO: 97-103. In some embodiments, Y of formula (VII) comprises a sequence having at least 90% identity with any of SEQ ID NO: 97-103. In some embodiments, Y of formula (VII) comprises a sequence having at least 95% identity with any of SEQ ID NO: 97-103.In some embodiments, the Y of formula (VII) comprises a sequence having at least 96%, at least 97%, at least 98%, or at least 99% identity with any of SEQ ID NO: 97-103. In some embodiments, the Y of formula (VII) comprises a sequence selected from any of SEQ ID NO: 97-103. In some embodiments, the Y of formula (VII) is a sequence selected from any of SEQ ID NO: 97-103.

[0183] In some embodiments, the artificial polypeptide of formula (VII) comprises a sequence having at least 70% identity with any of SEQ ID NO: 104-110. In some embodiments, the artificial polypeptide of formula (VII) comprises a sequence having at least 75% identity with any of SEQ ID NO: 104-110. In some embodiments, the artificial polypeptide of formula (VII) comprises a sequence having at least 80% identity with any of SEQ ID NO: 104-110. In some embodiments, the artificial polypeptide of formula (VII) comprises a sequence having at least 85% identity with any of SEQ ID NO: 104-110. In some embodiments, the artificial polypeptide of formula (VII) comprises a sequence having at least 90% identity with any of SEQ ID NO: 104-110. In some embodiments, the artificial polypeptide of formula (VII) comprises a sequence having at least 95% identity with any of SEQ ID NO: 104-110. In some embodiments, the artificial polypeptide of formula (VII) comprises a sequence having at least 96%, at least 97%, at least 98%, or at least 99% identity with any of SEQ ID NO: 104-110. In some embodiments, the artificial polypeptide of formula (VII) is any of the sequences selected from SEQ ID NO: 104-110.

[0184] In another aspect, a method is provided for treating or preventing allergic conjunctivitis in a subject in need, comprising administering to the subject an effective amount of a mutant of an artificial polypeptide of formula (I), X-Y (I), wherein X is a portion comprising a sequence having at least 80% identity with SEQ ID NO: 1, Y is a portion comprising 10 to 50 amino acids, at least 50% of which are selected from I, V, L, F, C, M and A, and Y comprises a total number of less than 5 cysteines (C), characterized in that the mutant mutates at least 1, 2, 3, 4, 5, 6, 7, 8 or 9 Ds in X to S, and / or mutates at least 1, 2, 3, 4, 5 or 6 Es in X to T.Specification page 42 / 68, 63 CN 121079312 A

[0185] In some embodiments, at least 20% of the amino acids in X of the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 25% of the amino acids in X of the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 30% of the amino acids in X of the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 35% of the amino acids in X of the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 40% of the amino acids in X of the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 45% of the amino acids in X of the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 50% of the amino acids in X of the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, up to 55% of the amino acids in mutant X are selected from R, K, N, D, Q, E, and H. In some embodiments, up to 60% of the amino acids in mutant X are selected from R, K, N, D, Q, E, and H. In some embodiments, up to 65% of the amino acids in mutant X are selected from R, K, N, D, Q, E, and H. In some embodiments, up to 70% of the amino acids in mutant X are selected from R, K, N, D, Q, E, and H. In some embodiments, up to 75% of the amino acids in mutant X are selected from R, K, N, D, Q, E, and H. In some embodiments, up to 80% of the amino acids in mutant X are selected from R, K, N, D, Q, E, and H. In some embodiments, up to 85% of the amino acids in mutant X are selected from R, K, N, D, Q, E, and H. In some embodiments, up to 90% of the amino acids in X of the mutant are selected from R, K, N, D, Q, E, and H.

[0186] In some embodiments, X of the mutant contains a sequence having at least 70% identity with SEQ ID NO: 1. In some embodiments, X of the mutant contains a sequence having at least 75% identity with SEQ ID NO: 1. In some embodiments, X of the mutant contains a sequence having at least 80% identity with SEQ ID NO: 1. In some embodiments, X of the mutant contains a sequence having at least 85% identity with SEQ ID NO: 1. In some embodiments, X of the mutant contains a sequence having at least 90% identity with SEQ ID NO: 1. In some embodiments, X of the mutant contains a sequence having at least 95% identity with SEQ ID NO: 1.

[0187] In some embodiments, Y in the mutant may be a portion containing 10 to 50 amino acids, and the total number of cysteine ​​(C) residues in Y is 5. In some embodiments, Y in the mutant may be a portion containing 10 to 50 amino acids, and the total number of cysteine ​​(C) residues in Y is less than 5. In some embodiments, Y in the mutant may be a portion containing 10 to 50 amino acids, and the total number of cysteine ​​(C) residues in Y is 4. In some embodiments, Y in the mutant may be a portion containing 10 to 50 amino acids, and the total number of cysteine ​​(C) residues in Y is less than 4. In some embodiments, Y in the mutant may be a portion containing 10 to 50 amino acids, and the total number of cysteine ​​(C) residues in Y is 3. In some embodiments, Y in the mutant may be a portion containing 10 to 50 amino acids, and the total number of cysteine ​​(C) residues in Y is less than 3. In some embodiments, Y in the mutant may be a portion containing 10 to 50 amino acids, and the total number of cysteine ​​(C) residues in Y is 2. In some embodiments, Y in the mutant may be a portion containing 10 to 50 amino acids, and the total number of cysteine ​​(C) in Y is less than 2. In some embodiments, Y in the mutant may be a portion containing 10 to 50 amino acids, and the total number of cysteine ​​(C) in Y is 1. In some embodiments, Y in the mutant may be a portion containing 10 to 50 amino acids, and the total number of cysteine ​​(C) in Y is less than 1. In some embodiments, Y in the mutant may be a portion containing 10 to 50 amino acids, and the total number of cysteine ​​(C) in Y is 0.

[0188] In some embodiments, the total number of hydrophobic amino acids in Y in the mutant is greater than 8. In some embodiments, the total number of hydrophobic amino acids in Y in the mutant is greater than 9. In some embodiments, the total number of hydrophobic amino acids in Y in the mutant is greater than 10. In some embodiments, the total number of hydrophobic amino acids in Y in the mutant is greater than 11. In some embodiments, the total number of hydrophobic amino acids in Y in the mutant is greater than 12. In some embodiments, the total number of hydrophobic amino acids in Y of the mutant is greater than 13. In some embodiments, the total number of hydrophobic amino acids in Y of the mutant is greater than 14. In some embodiments, the total number of hydrophobic amino acids in Y of the mutant is greater than 15.

[0189] In some embodiments, the total number of hydrophilic amino acids in Y of the mutant is 5. In some embodiments, the total number of hydrophilic amino acids in Y of the mutant is no more than 5. In some embodiments, the total number of hydrophilic amino acids in Y of the mutant is 4. In some embodiments, the total number of hydrophilic amino acids in Y of the mutant is no more than 4.In some embodiments, the total number of hydrophilic amino acids in Y of the mutant is 3. In some embodiments, the total number of hydrophilic amino acids in Y of the mutant is no more than 3. In some embodiments, the total number of hydrophilic amino acids in Y of the mutant is 2. In some embodiments, the total number of hydrophilic amino acids in Y of the mutant is no more than 2. In some embodiments, the total number of hydrophilic amino acids in Y of the mutant is 1. In some embodiments, the total number of hydrophilic amino acids in Y of the mutant is no more than 1.

[0190] In some embodiments, Y of the mutant contains a sequence having at least 70% identity with any one of SEQ ID NO: 3-15, 58-61, and 84-85. In some embodiments, Y of the mutant contains a sequence having at least 75% identity with any one of SEQ ID NO: 3-15, 58-61, and 84-85. In some embodiments, Y of the mutant contains a sequence having at least 80% identity with any one of SEQ ID NO: 3-15, 58-61, and 84-85. In some embodiments, the Y in the mutant contains a sequence having at least 85% identity with any one of SEQ ID NO: 3-15, 58-61, and 84-85. In some embodiments, the Y in the mutant contains a sequence having at least 90% identity with any one of SEQ ID NO: 3-15, 58-61, and 84-85. In some embodiments, the Y in the mutant contains a sequence having at least 95% identity with any one of SEQ ID NO: 3-15, 58-61, and 84-85. In some embodiments, the Y in the mutant contains a sequence having at least 96%, at least 97%, at least 98%, or at least 99% identity with any one of SEQ ID NO: 3-15, 58-61, and 84-85. In some embodiments, the Y in the mutant contains a sequence selected from any one of SEQ ID NO: 3-15, 58-61, and 84-85. In some embodiments, Y in the mutant is a sequence selected from any one of SEQ ID NO: 3-15, 58-61, and 84-85.

[0191] In some embodiments, Y in the mutant contains a sequence having at least 70% identity with any one of SEQ ID NO: 3-18, 58-61, and 84-85. In some embodiments, Y in the mutant contains a sequence having at least 75% identity with any one of SEQ ID NO: 3-18, 58-61, and 84-85.In some embodiments, the Y in the mutant contains a sequence having at least 80% identity with any one of SEQ ID NO: 3-18, 58-61, and 84-85. In some embodiments, the Y in the mutant contains a sequence having at least 85% identity with any one of SEQ ID NO: 3-18, 58-61, and 84-85. In some embodiments, the Y in the mutant contains a sequence having at least 90% identity with any one of SEQ ID NO: 3-18, 58-61, and 84-85. In some embodiments, the Y in the mutant contains a sequence having at least 95% identity with any one of SEQ ID NO: 3-18, 58-61, and 84-85. In some embodiments, the Y in the mutant contains a sequence having at least 96%, at least 97%, at least 98%, or at least 99% identity with any one of SEQ ID NO: 3-18, 58-61, and 84-85. In some embodiments, the Y in the mutant comprises a sequence selected from any one of SEQ ID NO: 3-18, 58-61, and 84-85. In some embodiments, the Y in the mutant is a sequence selected from any one of SEQ ID NO: 3-18, 58-61, and 84-85.

[0192] In another aspect, a method for treating or preventing allergic conjunctivitis in a subject in need is provided, comprising administering to the subject an effective amount of a mutant of an artificial polypeptide of formula (II), X-Y (II), wherein X is a portion comprising a sequence having at least 80% identity with SEQ ID NO: 1, Y is a portion comprising 10 to 50 amino acids, at least 50% of which are selected from I, V, L, F, C, M, and A, Y comprising a sequence having at most 90% identity with SEQ ID NO: 2, characterized in that the mutant mutates at least 1, 2, 3, 4, 5, 6, 7, 8, or 9 Ds in X to S, and / or mutates at least 1, 2, 3, 4, 5, or 6 Es in X to T. Specification 44 / 68 pages 65 CN 121079312 A

[0193] In some embodiments, at least 20% of the amino acids in X of the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 25% of the amino acids in X of the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 30% of the amino acids in X of the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 35% of the amino acids in X of the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 40% of the amino acids in X of the mutant are selected from R, K, N, D, Q, E, and H.In some embodiments, at least 45% of the amino acids in X of the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 50% of the amino acids in X of the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, up to 55% of the amino acids in X of the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, up to 60% of the amino acids in X of the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, up to 65% of the amino acids in X of the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, up to 70% of the amino acids in X of the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, up to 75% of the amino acids in X of the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, up to 80% of the amino acids in X of the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, up to 85% of the amino acids in X of the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, up to 90% of the amino acids in X of the mutant are selected from R, K, N, D, Q, E, and H.

[0194] In some embodiments, X of the mutant contains a sequence having at least 70% identity with SEQ ID NO: 1. In some embodiments, X of the mutant contains a sequence having at least 75% identity with SEQ ID NO: 1. In some embodiments, X of the mutant contains a sequence having at least 80% identity with SEQ ID NO: 1. In some embodiments, X of the mutant contains a sequence having at least 85% identity with SEQ ID NO: 1. In some embodiments, X of the mutant contains a sequence having at least 90% identity with SEQ ID NO: 1. In some embodiments, X in the mutant contains a sequence having at least 95% identity with SEQ ID NO: 1.

[0195] In some embodiments, Y in the mutant contains a sequence having at most 50% identity with SEQ ID NO: 2. In some embodiments, Y in the mutant contains a sequence having at most 55% identity with SEQ ID NO: 2. In some embodiments, Y in the mutant contains a sequence having at most 60% identity with SEQ ID NO: 2. In some embodiments, Y in the mutant contains a sequence having at most 65% identity with SEQ ID NO: 2. In some embodiments, Y in the mutant contains a sequence having at most 70% identity with SEQ ID NO: 2. In some embodiments, Y in the mutant contains a sequence having at most 75% identity with SEQ ID NO: 2.In some embodiments, the Y in the mutant contains a sequence having up to 80% identity with SEQ ID NO: 2. In some embodiments, the Y in the mutant contains a sequence having up to 85% identity with SEQ ID NO: 2. In some embodiments, the Y in the mutant contains a sequence having up to 90% identity with SEQ ID NO: 2.

[0196] In some embodiments, the total number of hydrophobic amino acids in the Y in the mutant is greater than 8. In some embodiments, the total number of hydrophobic amino acids in the Y in the mutant is greater than 9. In some embodiments, the total number of hydrophobic amino acids in the Y in the mutant is greater than 10. In some embodiments, the total number of hydrophobic amino acids in the Y in the mutant is greater than 11. In some embodiments, the total number of hydrophobic amino acids in the Y in the mutant is greater than 12. In some embodiments, the total number of hydrophobic amino acids in the Y in the mutant is greater than 13. In some embodiments, the total number of hydrophobic amino acids in the Y in the mutant is greater than 14. In some embodiments, the total number of hydrophobic amino acids in the Y in the mutant is greater than 15.

[0197] In some embodiments, the total number of hydrophilic amino acids in Y of the mutant is 5. In some embodiments, the total number of hydrophilic amino acids in Y of the mutant is no more than 5. In some embodiments, the total number of hydrophilic amino acids in Y of the mutant is 4. In some embodiments, the total number of hydrophilic amino acids in Y of the mutant is no more than 4. In some embodiments, the total number of hydrophilic amino acids in Y of the mutant is 3. In some embodiments, the total number of hydrophilic amino acids in Y of the mutant is no more than 3. In some embodiments, the total number of hydrophilic amino acids in Y of the mutant is the same as described on page 45 / 68 of the specification, CN 121079312 A 2. In some embodiments, the total number of hydrophilic amino acids in Y of the mutant is no more than 2. In some embodiments, the total number of hydrophilic amino acids in Y of the mutant is 1. In some embodiments, the total number of hydrophilic amino acids in Y of the mutant is no more than 1.

[0198] In some embodiments, the Y in the mutant contains a sequence having at least 70% identity with any of SEQ ID NO: 16-18. In some embodiments, the Y in the mutant contains a sequence having at least 75% identity with any of SEQ ID NO: 16-18. In some embodiments, the Y in the mutant contains a sequence having at least 80% identity with any of SEQ ID NO: 16-18. In some embodiments, the Y in the mutant contains a sequence having at least 85% identity with any of SEQ ID NO: 16-18.In some embodiments, the Y in the mutant comprises a sequence having at least 90% identity with any of SEQ ID NO: 16-18. In some embodiments, the Y in the mutant comprises a sequence having at least 95% identity with any of SEQ ID NO: 16-18. In some embodiments, the Y in the mutant comprises a sequence having at least 96%, at least 97%, at least 98%, or at least 99% identity with any of SEQ ID NO: 16-18. In some embodiments, the Y in the mutant is a sequence selected from any of SEQ ID NO: 16-18.

[0199] In another aspect, a method is provided for treating or preventing allergic conjunctivitis in a subject in need, comprising administering to the subject an effective amount of a mutant of an artificial polypeptide of formula (III), X-Y (III), wherein X is a portion comprising 40 to 65 amino acids, at least 50% of which are selected from H, R, K, D, Q, N, and E, Y is a portion comprising a sequence having at least 80% identity with SEQ ID NO: 2, the total number of H, R, K, D, Q, N, and E in X is less than 33, characterized in that the mutant mutates at least 1, 2, 3, 4, 5, 6, 7, 8, or 9 Ds in X to S, and / or mutates at least 1, 2, 3, 4, 5, or 6 Es in X to T.

[0200] In some embodiments, at least 20% of the amino acids in X of the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 25% of the amino acids in X of the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 30% of the amino acids in X of the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 35% of the amino acids in X of the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 40% of the amino acids in X of the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 45% of the amino acids in X of the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 50% of the amino acids in X of the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 55% of the amino acids in X of the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 60% of the amino acids in X of the mutant are selected from R, K, N, D, Q, E, and H. In some implementations, up to 65% of the amino acids in X of the mutant are selected from R, K, N, D, Q, E, and H.In some embodiments, up to 70% of the amino acids in X of the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, up to 75% of the amino acids in X of the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, up to 80% of the amino acids in X of the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, up to 85% of the amino acids in X of the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, up to 90% of the amino acids in X of the mutant are selected from R, K, N, D, Q, E, and H.

[0201] In some embodiments, X of the mutant is a portion containing 40 to 65 amino acids, and the total number of H, R, K, D, Q, N, and E in X is less than 33. In some embodiments, X of the mutant is a portion containing 40 to 65 amino acids, and the total number of H, R, K, D, Q, N, and E in X is less than 32. In some embodiments, X in the mutant is a portion containing 40 to 65 amino acids, and the total number of H, R, K, D, Q, N, and E in X is less than 31. In some embodiments, X in the mutant is a portion containing 40 to 65 amino acids, and the total number of H, R, K, D, Q, N, and E in X is less than 30. In some embodiments, X in the mutant is a portion containing 40 to 65 amino acids, and the total number of H, R, K, D, Q, N, and E in X is less than 29. In some embodiments, X in the mutant is a portion containing 40 to 65 amino acids, and the total number of H, R, K, D, Q, N, and E in X is less than 28. In some embodiments, X in the mutant is a portion containing 40 to 65 amino acids, and the total number of H, R, K, D, Q, N, and E in X is less than 27. In some embodiments, X in the mutant is a portion containing 40 to 65 amino acids, and the total number of H, R, K, D, Q, N, and E in X is less than 26. In some embodiments, X in the mutant is a portion containing 40 to 65 amino acids, and the total number of H, R, K, D, Q, N, and E in X is less than 25. In some embodiments, X in the mutant is a portion containing 40 to 65 amino acids, and the total number of H, R, K, D, Q, N, and E in X is less than 24. In some embodiments, X in the mutant is a portion containing 40 to 65 amino acids, and the total number of H, R, K, D, Q, N, and E in X is less than 23. In some embodiments, X in the mutant is a portion containing 40 to 65 amino acids, and the total number of H, R, K, D, Q, N, and E in X is less than 22. In some implementations, X in the mutant is a portion containing 40 to 65 amino acids, and the total number of H, R, K, D, Q, N, and E in X is less than 21.In some embodiments, X in the mutant is a portion containing 40 to 65 amino acids, and the total number of H, R, K, D, Q, N, and E in X is less than 20.

[0202] In some embodiments, X in the mutant is a portion containing 40 to 65 amino acids, and the total number of hydrophilic amino acids in X is greater than 10. In some embodiments, X in the mutant is a portion containing 40 to 65 amino acids, and the total number of hydrophilic amino acids in X is greater than 11. In some embodiments, X in the mutant is a portion containing 40 to 65 amino acids, and the total number of hydrophilic amino acids in X is greater than 12. In some embodiments, X in the mutant is a portion containing 40 to 65 amino acids, and the total number of hydrophilic amino acids in X is greater than 13. In some embodiments, X in the mutant is a portion containing 40 to 65 amino acids, and the total number of hydrophilic amino acids in X is greater than 14. In some embodiments, X in the mutant is a portion containing 40 to 65 amino acids, and the total number of hydrophilic amino acids in X is greater than 15. In some embodiments, X in the mutant is a portion containing 40 to 65 amino acids, and the total number of hydrophilic amino acids in X is greater than 16. In some embodiments, X in the mutant is a portion containing 40 to 65 amino acids, and the total number of hydrophilic amino acids in X is greater than 17. In some embodiments, X in the mutant is a portion containing 40 to 65 amino acids, and the total number of hydrophilic amino acids in X is greater than 18. In some embodiments, X in the mutant is a portion containing 40 to 65 amino acids, and the total number of hydrophilic amino acids in X is greater than 19. In some embodiments, X in the mutant is a portion containing 40 to 65 amino acids, and the total number of hydrophilic amino acids in X is greater than 20. In some embodiments, X in the mutant is a portion containing 40 to 65 amino acids, and the total number of hydrophilic amino acids in X is greater than 21. In some embodiments, X in the mutant is a portion containing 40 to 65 amino acids, and the total number of hydrophilic amino acids in X is greater than 22. In some embodiments, X in the mutant is a portion containing 40 to 65 amino acids, and the total number of hydrophilic amino acids in X is greater than 23. In some embodiments, X in the mutant is a portion containing 40 to 65 amino acids, and the total number of hydrophilic amino acids in X is greater than 24. In some embodiments, X in the mutant is a portion containing 40 to 65 amino acids, and the total number of hydrophilic amino acids in X is greater than 25.

[0203] In some embodiments, X in the mutant is a portion containing 40 to 65 amino acids, and the total number of hydrophobic amino acids in X is no more than 15. In some embodiments, X in the mutant is a portion containing 40 to 65 amino acids, and the total number of hydrophobic amino acids in X is no more than 14.In some embodiments, X in the mutant is a portion containing 40 to 65 amino acids, and the total number of hydrophobic amino acids in X does not exceed 13. In some embodiments, X in the mutant is a portion containing 40 to 65 amino acids, and the total number of hydrophobic amino acids in X does not exceed 12. In some embodiments, X in the mutant is a portion containing 40 to 65 amino acids, and the total number of hydrophobic amino acids in X does not exceed 11. In some embodiments, X in the mutant is a portion containing 40 to 65 amino acids, and the total number of hydrophobic amino acids in X does not exceed 10. In some embodiments, X in the mutant is a portion containing 40 to 65 amino acids, and the total number of hydrophobic amino acids in X does not exceed 5.

[0204] In some embodiments, X in the mutant contains a sequence having at least 70% identity with SEQ ID NO: 1. In some embodiments, X in the mutant contains a sequence having at least 75% identity with SEQ ID NO: 1. In some embodiments, X in the mutant comprises a sequence having at least 80% identity with SEQ ID NO: 1. In some embodiments, X in the mutant comprises a sequence having at least 85% identity with SEQ ID NO: 1. In some embodiments, X in the mutant comprises a sequence having at least 90% identity with SEQ ID NO: 1. In some embodiments, X in the mutant comprises a sequence having at least 95% identity with SEQ ID NO: 1.

[0205] In some embodiments, Y in the mutant is a portion comprising a sequence having at least 70% identity with SEQ ID NO: 2. In some embodiments, Y in the mutant is a portion comprising a sequence having at least 75% identity with SEQ ID NO: 2. In some embodiments, Y in the mutant is a portion comprising a sequence having at least 80% identity with SEQ ID NO: 2. In some embodiments, Y in the mutant is a portion comprising a sequence having at least 85% identity with SEQ ID NO: 2. In some embodiments, Y in the mutant is a portion comprising a sequence having at least 90% identity with SEQ ID NO: 2. In some embodiments, Y in the mutant is a portion containing a sequence having at least 95% identity with SEQ ID NO: 2. In some embodiments, Y in the mutant is a portion containing a sequence having at least 96%, at least 97%, at least 98%, or at least 99% identity with SEQ ID NO: 2. In some embodiments, Y in the mutant is a portion containing the sequence of SEQ ID NO: 2.In some embodiments, Y in the mutant is a portion of the sequence SEQ ID NO: 2.

[0206] In some embodiments, Y in the mutant is a hydrophobic portion, and at least 50% of the amino acids in Y are selected from I, V, L, F, C, M, and A. In some embodiments, Y in the mutant is a hydrophobic portion, and at least 55% of the amino acids in Y are selected from I, V, L, F, C, M, and A. In some embodiments, Y in the mutant is a hydrophobic portion, and at least 60% of the amino acids in Y are selected from I, V, L, F, C, M, and A. In some embodiments, Y in the mutant is a hydrophobic portion, and at least 65% of the amino acids in Y are selected from I, V, L, F, C, M, and A. In some embodiments, Y in the mutant is a hydrophobic portion, and at least 70% of the amino acids in Y are selected from I, V, L, F, C, M, and A. In some embodiments, Y in the mutant is a hydrophobic moiety, and at least 75% of the amino acids in Y are selected from I, V, L, F, C, M, and A. In some embodiments, Y in the mutant is a hydrophobic moiety, and at least 80% of the amino acids in Y are selected from I, V, L, F, C, M, and A. In some embodiments, Y in the mutant is a hydrophobic moiety, and at least 85% of the amino acids in Y are selected from I, V, L, F, C, M, and A. In some embodiments, Y in the mutant is a hydrophobic moiety, and at least 90% of the amino acids in Y are selected from I, V, L, F, C, M, and A.

[0207] In another aspect, a method is provided for treating or preventing allergic conjunctivitis in a subject in need, comprising administering to the subject an effective amount of a mutant of formula (IV) artificial polypeptide, X-Y (IV), wherein X is a portion comprising 40 to 65 amino acids, at least 50% of which are selected from H, R, K, D, Q, N, and E, Y is a portion comprising a sequence having at least 80% identity with SEQ ID NO: 2, and X comprises a sequence having at most 90% identity with SEQ ID NO: 1, characterized in that the mutant mutates at least 1, 2, 3, 4, 5, 6, 7, 8, or 9 Ds in X to S, and / or mutates at least 1, 2, 3, 4, 5, or 6 Es in X to T.

[0208] In some embodiments, at least 20% of the amino acids in X of the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, as described on pages 48 / 68 of the specification (CN 121079312 A), at least 25% of the amino acids in X of the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 30% of the amino acids in X of the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 35% of the amino acids in X of the mutant are selected from R, K, N, D, Q, E, and H.In some embodiments, at least 40% of the amino acids in X of the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 45% of the amino acids in X of the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 50% of the amino acids in X of the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, up to 55% of the amino acids in X of the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, up to 60% of the amino acids in X of the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, up to 65% of the amino acids in X of the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, up to 70% of the amino acids in X of the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, up to 75% of the amino acids in X of the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, up to 80% of the amino acids in X of the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, up to 85% of the amino acids in X of the mutant are selected from R, K, N, D, Q, E, and H. In some embodiments, up to 90% of the amino acids in X of the mutant are selected from R, K, N, D, Q, E, and H.

[0209] In some embodiments, X of the mutant contains 40 to 65 amino acids, and the total number of hydrophilic amino acids in X is greater than 10. In some embodiments, X of the mutant contains 40 to 65 amino acids, and the total number of hydrophilic amino acids in X is greater than 15. In some embodiments, X of the mutant contains 40 to 65 amino acids, and the total number of hydrophilic amino acids in X is greater than 20. In some embodiments, X of the mutant contains 40 to 65 amino acids, and the total number of hydrophilic amino acids in X is greater than 25. In some embodiments, X in the mutant comprises 40 to 65 amino acids, and the total number of hydrophilic amino acids in X is greater than 30. In some embodiments, X in the mutant comprises 40 to 65 amino acids, and the total number of hydrophilic amino acids in X is greater than 35.

[0210] In some embodiments, X in the mutant is a portion comprising 40 to 65 amino acids, and the total number of hydrophobic amino acids in X does not exceed 15. In some embodiments, X in the mutant is a portion comprising 40...

Claims

1. A method for treating or preventing allergic conjunctivitis in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of Formula (I): X-Y (I), wherein X is a moiety comprising a sequence that is at least 80% identical to SEQ ID NO: 1, and Y is a moiety comprising 10 to 50 amino acids, at least 50% of which are selected from I, V, L, F, C, M, and A; wherein the total number of cysteines (C) comprised by Y is less than 5.

2. The method of claim 1, wherein X comprises a sequence that is at least 90% identical to SEQ ID NO: 1, X comprises a sequence that is at least 95% identical to SEQ ID NO: 1, or X comprises the sequence of SEQ ID NO:

1.

3. The method of claim 1 or 2, wherein at least 50% of the amino acids in X are selected from R, K, N, D, Q, E, and H.

4. The method of any one of claims 1 to 3, wherein the total number of cysteines (C) comprised by Y is less than 4, the total number of cysteines (C) comprised by Y is less than 3, or the total number of cysteines (C) comprised by Y is less than 2.

5. The method of any one of claims 1 to 4, wherein the total number of hydrophobic amino acids in Y is greater than 8, the total number of hydrophobic amino acids in Y is greater than 12, the total number of hydrophobic amino acids in Y is greater than 15, and / or the total number of hydrophilic amino acids in Y is no more than 5.

6. The method of any one of claims 1 to 5, wherein X comprises a sequence that is at least 90% identical to any one selected from the group consisting of SEQ ID NOs: 81-83.

7. The method of any one of claims 1 to 6, wherein Y comprises a sequence that is at least 90% identical to any one selected from the group consisting of SEQ ID NOs: 3-15, 58-61, and 84-85, or Y comprises a sequence that is at least 90% identical to any one selected from the group consisting of SEQ ID NOs: 3-18, 58-61, and 84-85.

8. The method of any one of claims 1 to 7, wherein the polypeptide comprises a sequence that is at least 90% identical to any one selected from the group consisting of SEQ ID NOs: 29-41, 54-57, 75, and 91-95.

9. The method of any one of claims 1 to 8, wherein the allergic conjunctivitis is at least one selected from the group consisting of seasonal allergic conjunctivitis, perennial allergic conjunctivitis, vernal keratoconjunctivitis, giant papillary conjunctivitis, atopic keratoconjunctivitis, and vesicular keratoconjunctivitis.

10. The method of claim 9, wherein the seasonal allergic conjunctivitis is caused by or partially caused by a seasonal allergen.

11. The method of claim 10, wherein the seasonal allergen is at least one selected from the group consisting of tree pollen, weed pollen, grass pollen, and mold spores.

12. The method of claim 9, wherein the perennial allergic conjunctivitis is caused by or partially caused by a perennial allergen. ​ ​ ​ ​ 13. The method of claim 12, wherein the perennial allergen is at least one selected from dust mites, cockroaches, and animal dander.

14. The method of claim 9, wherein the vernal keratoconjunctivitis is at least one selected from lid vernal keratoconjunctivitis, limbal vernal keratoconjunctivitis, and mixed vernal keratoconjunctivitis.

15. The method of claim 9, wherein the giant papillary conjunctivitis is caused by or is partially caused by repeated mechanical irritation of the conjunctiva.

16. The method of claim 15, wherein the repeated mechanical irritation of the conjunctiva is associated with at least one selected from the group consisting of contact lens wear, use of ocular prosthesis, use of conjunctival sutures, use of prominent scleral buckling, and corneal scar elevation.

17. The method of claim 9, wherein the atopic keratoconjunctivitis is accompanied by atopic dermatitis and / or asthma.

18. The method of claim 9, wherein the vesicular keratoconjunctivitis is caused by or is partially caused by a delayed hypersensitivity reaction or an inflammatory reaction of the cornea and conjunctiva to antigens expressed by various pathogens.

19. The method of claim 18, wherein the pathogen is at least one selected from the group consisting of bacteria (e.g., Staphylococcus aureus, Streptococcus viridans, Mycobacterium tuberculosis), viruses (e.g., herpes simplex virus), chlamydia, fungi (e.g., Candida such as Candida albicans), and parasites (e.g., tapeworms such as Hymenolepis microstoma; and nematodes).

20. The method of any one of claims 1 to 19, wherein the subject does not have any ocular disease selected from the group consisting of viral conjunctivitis, bacterial conjunctivitis, chemical conjunctivitis, and dry eye or dry eye related disorders.

21. The method of any one of claims 1 to 20, wherein the subject experiences at least one symptom selected from the group consisting of conjunctival redness, conjunctival edema, conjunctival hyperemia, eyelid redness, eyelid edema, eyelid hyperemia, ocular itch, corneal visible lesions, mucous discharge, watery discharge, tearing, photophobia, foreign body sensation, and difficulty opening the eye prior to administration of the artificial polypeptide of formula (I).

22. The method of any one of claims 1 to 21, wherein the subject shows a reduction in at least one symptom selected from the group consisting of conjunctival redness, conjunctival edema, conjunctival hyperemia, eyelid redness, eyelid edema, eyelid hyperemia, ocular itch, corneal visible lesions, mucous discharge, watery discharge, tearing, photophobia, foreign body sensation, and difficulty opening the eye after administration of at least one dose of the artificial polypeptide of formula (I).

23. The method of any one of claims 1 to 22, wherein the subject shows an improvement in at least one tissue selected from the group consisting of conjunctiva, cornea, anterior chamber, iris, pupil, vitreous, and fundus after administration of at least one dose of the artificial polypeptide of formula (I).

24. A method for treating or preventing allergic conjunctivitis in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (II): X-Y (II), wherein X is a moiety comprising a sequence that is at least 80% identical to SEQ ID NO: 1, and Y is a moiety comprising a sequence that is at least 80% identical to SEQ ID NO:

2. ​ ​ Y is a moiety comprising 10 to 50 amino acids, at least 50% of which are selected from I, V, L, F, C, M, and A; wherein Y comprises a sequence that is at most 90% identical to SEQ ID NO:

2.

25. The method of claim 24, wherein X comprises a sequence that is at least 90% identical to SEQ ID NO: 1, X comprises a sequence that is at least 95% identical to SEQ ID NO: 1, or X comprises the sequence of SEQ ID NO:

1.

26. The method of claim 24 or 25, wherein at least 50% of the amino acids in X are selected from R, K, N, D, Q, E, and H.

27. The method of any one of claims 24 to 26, wherein Y comprises a sequence that is at most 80% identical to SEQ ID NO: 2, Y comprises a sequence that is at most 70% identical to SEQ ID NO: 2, or Y comprises a sequence that is at most 50% identical to SEQ ID NO:

2.

28. The method of any one of claims 24 to 27, wherein the total number of hydrophobic amino acids in Y is greater than 8, the total number of hydrophobic amino acids in Y is greater than 12, the total number of hydrophobic amino acids in Y is greater than 15, and / or the total number of hydrophilic amino acids in Y is no more than 5.

29. The method of any one of claims 24 to 28, wherein Y comprises a sequence that is at least 90% identical to any one selected from the group consisting of SEQ ID NOs: 16-18, or Y comprises a sequence that is at least 95% identical to any one selected from the group consisting of SEQ ID NOs: 16-18.

30. The method of any one of claims 24 to 29, wherein the polypeptide comprises a sequence that is at least 90% identical to any one selected from the group consisting of SEQ ID NOs: 42-44.

31. The method of any one of claims 24 to 30, wherein the allergic conjunctivitis is at least one selected from the group consisting of seasonal allergic conjunctivitis, perennial allergic conjunctivitis, vernal keratoconjunctivitis, giant papillary conjunctivitis, atopic keratoconjunctivitis, and bullous keratoconjunctivitis.

32. The method of claim 31, wherein the seasonal allergic conjunctivitis is caused by or partially caused by a seasonal allergen.

33. The method of claim 32, wherein the seasonal allergen is at least one selected from the group consisting of tree pollen, weed pollen, grass pollen, and mold spores.

34. The method of claim 31, wherein the perennial allergic conjunctivitis is caused by or partially caused by a perennial allergen.

35. The method of claim 34, wherein the perennial allergen is at least one selected from the group consisting of dust mites, cockroaches, and animal dander.

36. The method of claim 31, wherein the vernal keratoconjunctivitis is at least one selected from the group consisting of lid vernal keratoconjunctivitis, limbal vernal keratoconjunctivitis, and mixed vernal keratoconjunctivitis.

37. The method of claim 31, wherein the giant papillary conjunctivitis is caused by or is partially caused by repeated mechanical irritation of the conjunctiva.

38. The method of claim 37, wherein the repeated mechanical irritation of the conjunctiva is associated with at least one selected from the group consisting of contact lens wear, use of ocular prosthesis, use of conjunctival sutures, use of prominent scleral banding, and corneal pannus.

39. The method of claim 31, wherein the atopic keratoconjunctivitis is accompanied by atopic dermatitis and / or asthma.

40. The method of claim 31, wherein the vesicular keratoconjunctivitis is caused by or is partially caused by a delayed hypersensitivity reaction or an inflammatory reaction of the cornea and conjunctiva to antigens expressed by various pathogens.

41. The method of claim 40, wherein the pathogen is at least one selected from the group consisting of bacteria (e.g., Staphylococcus aureus, Streptococcus viridans, Mycobacterium tuberculosis), viruses (e.g., herpes simplex virus), chlamydia, fungi (e.g., Candida such as Candida albicans), and parasites (e.g., tapeworms such as Hymenolepis microstoma; and nematodes).

42. The method of any one of claims 24 to 41, wherein the subject does not have any ocular disease selected from the group consisting of viral conjunctivitis, bacterial conjunctivitis, chemical conjunctivitis, and dry eye or dry eye related conditions.

43. The method of any one of claims 24 to 42, wherein the subject experiences at least one symptom selected from the group consisting of conjunctival redness, conjunctival edema, conjunctival hyperemia, eyelid redness, eyelid edema, eyelid hyperemia, ocular itch, corneal visible lesions, mucous discharge, watery discharge, tearing, photophobia, foreign body sensation, and difficulty opening the eye prior to administration of the artificial polypeptide of formula (II).

44. The method of any one of claims 24 to 43, wherein the subject shows a reduction in at least one symptom selected from the group consisting of conjunctival redness, conjunctival edema, conjunctival hyperemia, eyelid redness, eyelid edema, eyelid hyperemia, ocular itch, corneal visible lesions, mucous discharge, watery discharge, tearing, photophobia, foreign body sensation, and difficulty opening the eye after administration of at least one dose of the artificial polypeptide of formula (II).

45. The method of any one of claims 24 to 44, wherein the subject shows an improvement in at least one tissue selected from the group consisting of conjunctiva, cornea, anterior chamber, iris, pupil, vitreous, and fundus after administration of at least one dose of the artificial polypeptide of formula (II).

46. A method for treating or preventing allergic conjunctivitis in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of formula (III): X-Y (III), wherein X is a moiety comprising 40 to 65 amino acids, at least 50% of which are selected from the group consisting of H, R, K, D, Q, N, and E; and Y is a moiety comprising a sequence that is at least 80% identical to SEQ ID NO: 2, wherein the total number of H, R, K, D, Q, N, and E in X is less than 33. ​ ​ ​ ​ 47. The method of claim 46, wherein Y comprises a sequence that is at least 90% identical to SEQ ID NO: 2, Y comprises a sequence that is at least 95% identical to SEQ ID NO: 2, or Y comprises the sequence of SEQ ID NO:

2.

48. The method of claim 46 or 47, wherein at least 50% of the amino acids in Y are selected from the group consisting of I, V, L, F, C, M, and A.

49. The method of any one of claims 46-48, wherein the total number of H, R, K, D, Q, N, and E in X is less than 30, the total number of H, R, K, D, Q, N, and E in X is less than 25, or the total number of H, R, K, D, Q, N, and E in X is less than 20.

50. The method of any one of claims 46-49, wherein the total number of hydrophilic amino acids in X is greater than 10, the total number of hydrophilic amino acids in X is greater than 15, the total number of hydrophilic amino acids in X is greater than 20, the total number of hydrophilic amino acids in X is greater than 25, the total number of hydrophobic amino acids in X is no more than 15, and / or the total number of hydrophobic amino acids in X is no more than 10.

51. The method of any one of claims 46-50, wherein X comprises a sequence that is at least 90% identical to any one selected from the group consisting of SEQ ID NOs: 23-27, or X comprises a sequence that is at least 95% identical to any one selected from the group consisting of SEQ ID NOs: 23-27.

52. The method of any one of claims 46-51, wherein the polypeptide comprises a sequence that is at least 90% identical to any one selected from the group consisting of SEQ ID NOs: 49-53.

53. The method of any one of claims 46-52, wherein the allergic conjunctivitis is at least one selected from the group consisting of seasonal allergic conjunctivitis, perennial allergic conjunctivitis, vernal keratoconjunctivitis, giant papillary conjunctivitis, atopic keratoconjunctivitis, and bullous keratoconjunctivitis.

54. The method of claim 53, wherein the seasonal allergic conjunctivitis is caused by or partially caused by a seasonal allergen.

55. The method of claim 54, wherein the seasonal allergen is at least one selected from the group consisting of tree pollen, weed pollen, grass pollen, and mold spores.

56. The method of claim 53, wherein the perennial allergic conjunctivitis is caused by or partially caused by a perennial allergen.

57. The method of claim 56, wherein the perennial allergen is at least one selected from the group consisting of dust mites, cockroaches, and animal dander.

58. The method of claim 53, wherein the vernal keratoconjunctivitis is at least one selected from the group consisting of lid vernal keratoconjunctivitis, limbal vernal keratoconjunctivitis, and mixed vernal keratoconjunctivitis.

59. The method of claim 53, wherein the giant papillary conjunctivitis is caused by or partially caused by repeated mechanical irritation of the conjunctiva.

60. The method of claim 59, wherein the repeated mechanical stimulation of the conjunctiva is associated with at least one selected from the group consisting of contact lens wear, use of an ocular prosthesis, use of conjunctival sutures, use of prominent scleral banding, and corneal scar elevation.

61. The method of claim 53, wherein the atopic keratoconjunctivitis is accompanied by atopic dermatitis and / or asthma.

62. The method of claim 53, wherein the vesicular keratoconjunctivitis is caused by or partially caused by a delayed hypersensitivity reaction or inflammatory reaction of the cornea and conjunctiva to antigens expressed by various pathogens.

63. The method of claim 62, wherein the pathogen is at least one selected from the group consisting of bacteria (e.g., Staphylococcus aureus, Streptococcus viridans, Mycobacterium tuberculosis), viruses (e.g., herpes simplex virus), chlamydia, fungi (e.g., Candida such as Candida albicans), and parasites (e.g., tapeworms such as Hymenolepis microstoma; and nematodes).

64. The method of any one of claims 46-63, wherein the subject does not have any ocular disease selected from the group consisting of viral conjunctivitis, bacterial conjunctivitis, chemical conjunctivitis, and dry eye or dry eye related conditions.

65. The method of any one of claims 46-64, wherein the subject experiences at least one symptom selected from the group consisting of conjunctival redness, conjunctival edema, conjunctival hyperemia, eyelid redness, eyelid edema, eyelid hyperemia, ocular itch, corneal visible lesions, mucous discharge, watery discharge, tearing, photophobia, foreign body sensation, and difficulty opening the eye prior to administration of the artificial polypeptide of Formula (III).

66. The method of any one of claims 46-65, wherein the subject exhibits a reduction in at least one symptom selected from the group consisting of conjunctival redness, conjunctival edema, conjunctival hyperemia, eyelid redness, eyelid edema, eyelid hyperemia, ocular itch, corneal visible lesions, mucous discharge, watery discharge, tearing, photophobia, foreign body sensation, and difficulty opening the eye after administration of at least one dose of the artificial polypeptide of Formula (III).

67. The method of any one of claims 46-66, wherein the subject exhibits an improvement in at least one tissue selected from the group consisting of conjunctiva, cornea, anterior chamber, iris, pupil, vitreous, and fundus after administration of at least one dose of the artificial polypeptide of Formula (III).

68. A method for treating or preventing allergic conjunctivitis in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of Formula (IV): X-Y (IV), wherein X is a moiety comprising 40 to 65 amino acids, at least 50% of which are selected from the group consisting of H, R, K, D, Q, N, and E; and Y is a moiety comprising a sequence that is at least 80% identical to SEQ ID NO: 2, wherein X comprises a sequence that is at most 90% identical to SEQ ID NO:

1. ​ ​ ​ ​ 69. The method of claim 68, wherein X comprises a sequence that is at most 80% identical to SEQ ID NO: 1, X comprises a sequence that is at most 70% identical to SEQ ID NO: 1, or X comprises a sequence that is at most 50% identical to SEQ ID NO:

1.

70. The method of claim 68 or 69, wherein Y comprises a sequence that is at least 90% identical to SEQ ID NO: 2, Y comprises a sequence that is at least 95% identical to SEQ ID NO: 2, or Y comprises the sequence of SEQ ID NO:

2.

71. The method of any one of claims 68-70, wherein at least 50% of the amino acids in Y are selected from the group consisting of I, V, L, F, C, M, and A.

72. The method of any one of claims 68-71, wherein the total number of hydrophilic amino acids in X is greater than 10, the total number of hydrophilic amino acids in X is greater than 15, the total number of hydrophilic amino acids in X is greater than 20, the total number of hydrophilic amino acids in X is greater than 25, the total number of hydrophobic amino acids in X is no more than 15, and / or the total number of hydrophobic amino acids in X is no more than 10.

73. The method of any one of claims 68-72, wherein X comprises a sequence that is at least 90% identical to any one selected from the group consisting of SEQ ID NOs: 19-22 and 76-79, or X comprises a sequence that is at least 95% identical to any one selected from the group consisting of SEQ ID NOs: 19-22 and 76-79.

74. The method of any one of claims 68-73, wherein the polypeptide comprises a sequence that is at least 90% identical to any one selected from the group consisting of SEQ ID NOs: 45-48 and 86-89.

75. The method of any one of claims 68-74, wherein the allergic conjunctivitis is at least one selected from the group consisting of seasonal allergic conjunctivitis, perennial allergic conjunctivitis, vernal keratoconjunctivitis, giant papillary conjunctivitis, atopic keratoconjunctivitis, and bullous keratoconjunctivitis.

76. The method of claim 75, wherein the seasonal allergic conjunctivitis is caused by or partially caused by a seasonal allergen.

77. The method of claim 76, wherein the seasonal allergen is at least one selected from the group consisting of tree pollen, weed pollen, grass pollen, and mold spores.

78. The method of claim 75, wherein the perennial allergic conjunctivitis is caused by or partially caused by a perennial allergen.

79. The method of claim 78, wherein the perennial allergen is at least one selected from the group consisting of dust mites, cockroaches, and animal dander.

80. The method of claim 75, wherein the vernal keratoconjunctivitis is at least one selected from the group consisting of eyelid vernal keratoconjunctivitis, limbal vernal keratoconjunctivitis, and mixed vernal keratoconjunctivitis.

81. The method of claim 75, wherein the giant papillary conjunctivitis is caused by or is partially caused by repeated mechanical irritation of the conjunctiva.

82. The method of claim 81, wherein the repeated mechanical irritation of the conjunctiva is associated with at least one selected from the group consisting of contact lens wear, use of ocular prosthesis, use of conjunctival sutures, use of prominent scleral buckling, and corneal pannus.

83. The method of claim 75, wherein the atopic keratoconjunctivitis is accompanied by atopic dermatitis and / or asthma.

84. The method of claim 75, wherein the vesicular keratoconjunctivitis is caused by or is partially caused by a delayed hypersensitivity reaction or inflammatory reaction of the cornea and conjunctiva to antigens expressed by various pathogens.

85. The method of claim 84, wherein the pathogen is at least one selected from the group consisting of bacteria (e.g., Staphylococcus aureus, Streptococcus viridans, Mycobacterium tuberculosis), viruses (e.g., herpes simplex virus), chlamydia, fungi (e.g., Candida such as Candida albicans), and parasites (e.g., tapeworms such as Hymenolepis microstoma; and nematodes).

86. The method of any one of claims 68-85, wherein the subject does not have any ocular disease selected from the group consisting of viral conjunctivitis, bacterial conjunctivitis, chemical conjunctivitis, and dry eye or dry eye related conditions.

87. The method of any one of claims 68-86, wherein the subject experiences at least one symptom selected from the group consisting of conjunctival redness, conjunctival edema, conjunctival hyperemia, eyelid redness, eyelid edema, eyelid hyperemia, ocular itch, corneal visible lesions, mucous discharge, watery discharge, tearing, photophobia, foreign body sensation, and difficulty opening the eye prior to administration of the artificial polypeptide of Formula (IV).

88. The method of any one of claims 68-87, wherein the subject shows a reduction in at least one symptom selected from the group consisting of conjunctival redness, conjunctival edema, conjunctival hyperemia, eyelid redness, eyelid edema, eyelid hyperemia, ocular itch, corneal visible lesions, mucous discharge, watery discharge, tearing, photophobia, foreign body sensation, and difficulty opening the eye after administration of at least one dose of the artificial polypeptide of Formula (IV).

89. The method of any one of claims 68-88, wherein the subject shows an improvement in at least one tissue selected from the group consisting of conjunctiva, cornea, anterior chamber, iris, pupil, vitreous, and fundus after administration of at least one dose of the artificial polypeptide of Formula (IV).

90. A method for treating or preventing allergic conjunctivitis in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of Formula (V): X-Y (V), wherein X is a moiety comprising a sequence that is at least 80% identical to SEQ ID NO: 1, and Y is a moiety comprising 10 to 30 amino acids, wherein Y comprises a sequence having at least 10 contiguous AAs in SEQ ID NO:

2. ​ ​ ​ 91. The method of claim 90, wherein Y comprises 10 to 25 amino acids, Y comprises 10 to 20 amino acids, or Y comprises 10 to 15 amino acids.

92. The method of claim 90 or 91, wherein X comprises a sequence that is at least 90% identical to SEQ ID NO: 1, X comprises a sequence that is at least 95% identical to SEQ ID NO: 1, or X comprises the sequence of SEQ ID NO:

1.

93. The method of any one of claims 90 to 92, wherein at least 50% of the amino acids in X are selected from R, K, N, D, Q, E, and H.

94. The method of any one of claims 90 to 93, wherein X comprises a sequence that is at least 80% identical to SEQ ID NO: 96, X comprises a sequence that is at least 90% identical to SEQ ID NO: 96, X comprises a sequence that is at least 95% identical to SEQ ID NO: 96, or X comprises the sequence of SEQ ID NO:

96.

95. The method of any one of claims 90 to 94, wherein Y comprises a sequence that is at most 80% identical to SEQ ID NO: 2, Y comprises a sequence that is at most 70% identical to SEQ ID NO: 2, or Y comprises a sequence that is at most 50% identical to SEQ ID NO:

2.

96. The method of any one of claims 90 to 95, wherein Y comprises a sequence that is at least 80% identical to any one selected from the group consisting of SEQ ID NOs: 97-103, Y comprises a sequence that is at least 90% identical to any one selected from the group consisting of SEQ ID NOs: 97-103, Y comprises a sequence that is at least 95% identical to any one selected from the group consisting of SEQ ID NOs: 97-103, or Y comprises a sequence of any one selected from the group consisting of SEQ ID NOs: 97-103.

97. The method of any one of claims 90 to 96, wherein the polypeptide comprises a sequence that is at least 90% identical to any one selected from the group consisting of SEQ ID NOs: 53-56 and 104-110.

98. The method of any one of claims 90 to 97, wherein the allergic conjunctivitis is at least one selected from the group consisting of seasonal allergic conjunctivitis, perennial allergic conjunctivitis, vernal keratoconjunctivitis, giant papillary conjunctivitis, atopic keratoconjunctivitis, and bullous keratoconjunctivitis.

99. The method of claim 98, wherein the seasonal allergic conjunctivitis is caused by or partially caused by a seasonal allergen.

100. The method of claim 99, wherein the seasonal allergen is at least one selected from the group consisting of tree pollen, weed pollen, grass pollen, and mold spores.

101. The method of claim 98, wherein the perennial allergic conjunctivitis is caused by or partially caused by a perennial allergen.

102. The method of claim 101, wherein the perennial allergen is at least one selected from dust mites, cockroaches, and animal dander.

103. The method of claim 98, wherein the vernal keratoconjunctivitis is at least one selected from lid vernal keratoconjunctivitis, limbal vernal keratoconjunctivitis, and mixed vernal keratoconjunctivitis.

104. The method of claim 98, wherein the giant papillary conjunctivitis is caused by or is partially caused by repeated mechanical irritation of the conjunctiva.

105. The method of claim 104, wherein the repeated mechanical irritation of the conjunctiva is associated with at least one selected from the group consisting of contact lens wear, use of ocular prosthesis, use of conjunctival sutures, use of prominent scleral buckling, and corneal scar elevation.

106. The method of claim 98, wherein the atopic keratoconjunctivitis is accompanied by atopic dermatitis and / or asthma.

107. The method of claim 98, wherein the vesicular keratoconjunctivitis is caused by or is partially caused by a delayed hypersensitivity reaction or an inflammatory reaction of the cornea and conjunctiva to antigens expressed by various pathogens.

108. The method of claim 107, wherein the pathogen is at least one selected from the group consisting of bacteria (e.g., Staphylococcus aureus, Streptococcus viridans, Mycobacterium tuberculosis), viruses (e.g., herpes simplex virus), chlamydia, fungi (e.g., Candida such as Candida albicans), and parasites (e.g., tapeworms such as Hymenolepis microstoma; and nematodes).

109. The method of any one of claims 90-108, wherein the subject does not have any ocular disease selected from the group consisting of viral conjunctivitis, bacterial conjunctivitis, chemical conjunctivitis, and dry eye or dry eye related disorders.

110. The method of any one of claims 90-109, wherein the subject experiences at least one symptom selected from the group consisting of conjunctival redness, conjunctival edema, conjunctival hyperemia, eyelid redness, eyelid edema, eyelid hyperemia, ocular itch, corneal visible lesions, mucous discharge, watery discharge, tearing, photophobia, foreign body sensation, and difficulty opening the eye prior to administration of the artificial polypeptide of Formula (V).

111. The method of any one of claims 90-110, wherein the subject exhibits a reduction in at least one symptom selected from the group consisting of conjunctival redness, conjunctival edema, conjunctival hyperemia, eyelid redness, eyelid edema, eyelid hyperemia, ocular itch, corneal visible lesions, mucous discharge, watery discharge, tearing, photophobia, foreign body sensation, and difficulty opening the eye after administration of at least one dose of the artificial polypeptide of Formula (V).

112. The method of any one of claims 90-111, wherein the subject exhibits an improvement in at least one tissue selected from the group consisting of conjunctiva, cornea, anterior chamber, iris, pupil, vitreous, and fundus after administration of at least one dose of the artificial polypeptide of Formula (V).

113. A method for treating or preventing allergic conjunctivitis in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of Formula (VI): X-Y (VI), ​ wherein X is a portion of a mutant comprising the sequence of SEQ ID NO: 1, characterized in that the mutant has at least 1, 2, 3, 4, 5, 6, 7, 8, or 9 Ds in SEQ ID NO: 1 mutated to S, and / or at least 1, 2, 3, 4, 5, or 6 Es in SEQ ID NO: 1 mutated to T; and Y is a portion of a mutant comprising the sequence of SEQ ID NO: 2, characterized in that the mutant has at least 1, 2, 3, 4, or 5 Cs in SEQ ID NO: 2 mutated to A.

114. The method of claim 113, wherein X comprises a sequence that is at least 70% identical to SEQ ID NO: 1, and / or X comprises a sequence that is at most 95% identical to SEQ ID NO:

1.

115. The method of claim 113 or 114, wherein Y comprises a sequence that is at least 80% identical to SEQ ID NO: 2, and / or Y comprises a sequence that is at most 95% identical to SEQ ID NO:

2.

116. The method of any one of claims 113-115, wherein at least 50% of the amino acids in Y are selected from the group consisting of I, V, L, F, C, M, and A.

117. The method of any one of claims 113-116, wherein the total number of R, K, T, A, N, Q, D, E, S, and G in X is greater than 30, and / or the total number of W, Y, F, M, L, I, and V in X is no more than 20.

118. The method of any one of claims 113-117, wherein the total number of R, K, T, A, N, Q, D, E, S, and G in Y is greater than 10, and / or the total number of W, Y, F, M, L, I, and V in Y is no more than 20.

119. The method of any one of claims 113-118, wherein X comprises a sequence that is at least 80% identical to any one selected from the group consisting of SEQ ID NOs: 80-83, X comprises a sequence selected from the group consisting of any one of SEQ ID NOs: 80-83, or X is a sequence selected from the group consisting of any one of SEQ ID NOs: 80-83.

120. The method of any one of claims 113-119, wherein Y comprises a sequence that is at least 80% identical to SEQ ID NO: 3, Y comprises the sequence of SEQ ID NO: 3, or Y is the sequence of SEQ ID NO:

3.

121. The method of any one of claims 113-120, wherein the artificial polypeptide comprises a sequence that is at least 80% identical to any one selected from the group consisting of SEQ ID NOs: 90-93, the artificial polypeptide comprises a sequence selected from the group consisting of any one of SEQ ID NOs: 90-93, or the artificial polypeptide is a sequence selected from the group consisting of any one of SEQ ID NOs: 90-93.

122. The method of any one of claims 113-121, wherein the allergic conjunctivitis is at least one selected from seasonal allergic conjunctivitis, perennial allergic conjunctivitis, vernal keratoconjunctivitis, giant papillary conjunctivitis, atopic keratoconjunctivitis, and vesicular keratoconjunctivitis.

123. The method of claim 122, wherein the seasonal allergic conjunctivitis is caused by or is partially caused by seasonal allergens.

124. The method of claim 123, wherein the seasonal allergens are at least one selected from tree pollen, weed pollen, grass pollen, and mold spores.

125. The method of claim 122, wherein the perennial allergic conjunctivitis is caused by or is partially caused by perennial allergens.

126. The method of claim 125, wherein the perennial allergens are at least one selected from dust mites, cockroaches, and animal dander.

127. The method of claim 122, wherein the vernal keratoconjunctivitis is at least one selected from lid vernal keratoconjunctivitis, limbal vernal keratoconjunctivitis, and mixed vernal keratoconjunctivitis.

128. The method of claim 122, wherein the giant papillary conjunctivitis is caused by or is partially caused by repeated mechanical irritation of the conjunctiva.

129. The method of claim 128, wherein the repeated mechanical irritation of the conjunctiva is associated with at least one selected from the group consisting of contact lens wear, use of ocular prosthesis, use of conjunctival sutures, use of prominent scleral buckling, and corneal scarring.

130. The method of claim 122, wherein the atopic keratoconjunctivitis is accompanied by atopic dermatitis and / or asthma.

131. The method of claim 122, wherein the vesicular keratoconjunctivitis is caused by or is partially caused by a delayed hypersensitivity reaction or an inflammatory reaction of the cornea and conjunctiva to antigens expressed by various pathogens.

132. The method of claim 131, wherein the pathogens are at least one selected from the group consisting of bacteria (e.g., Staphylococcus aureus, Streptococcus viridans, Mycobacterium tuberculosis), viruses (e.g., herpes simplex virus), chlamydia, fungi (e.g., Candida such as Candida albicans), and parasites (e.g., tapeworms such as Hymenolepis microstoma; and nematodes).

133. The method of any one of claims 113-132, wherein the subject does not have any ocular disease selected from the group consisting of viral conjunctivitis, bacterial conjunctivitis, chemical conjunctivitis, and dry eye or dry eye related disorders.

134. The method of any one of claims 113-133, wherein the subject experiences at least one symptom selected from the group consisting of conjunctival redness, conjunctival edema, conjunctival hyperemia, eyelid redness, eyelid edema, eyelid hyperemia, ocular itch, corneal visible lesions, mucous discharge, watery discharge, tearing, photophobia, foreign body sensation, and difficulty opening the eye prior to administration of the artificial polypeptide of Formula (VI).

135. The method of any one of claims 113-134, wherein the subject exhibits a reduction in at least one symptom selected from the group consisting of conjunctival redness, conjunctival edema, conjunctival hyperemia, eyelid redness, eyelid edema, eyelid hyperemia, ocular itching, corneal visible lesions, mucous discharge, watery discharge, tearing, photophobia, foreign body sensation, and difficulty opening the eye, following administration of at least one dose of the artificial polypeptide of Formula (VI).

136. The method of any one of claims 113-135, wherein the subject exhibits an improvement in at least one tissue selected from the group consisting of conjunctiva, cornea, anterior chamber, iris, pupil, vitreous, and fundus, following administration of at least one dose of the artificial polypeptide of Formula (VI).

137. A method for treating or preventing allergic conjunctivitis in a subject in need thereof, comprising administering to the subject an effective amount of an artificial polypeptide of Formula (VII): X-Y (VII), the mutant having at least 1, 2, 3, 4, or 5 amino acid insertions relative to SEQ ID NO: 1, and Y is a moiety comprising 10 to 30 amino acids, wherein Y comprises a sequence having at least 15 contiguous AA of SEQ ID NO:

2. wherein X is a portion of a mutant comprising the sequence of SEQ ID NO: 1, characterized in that 138. The method of claim 137, wherein the amino acid insertions are located N-terminal to X, and / or the inserted amino acids are M. the mutant having at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid truncations relative to SEQ ID NO: 2, and optionally, the at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid truncations are located C-terminal to Y.

140. The method of any one of claims 137-139, wherein at least 50% of the amino acids in X are selected from the group consisting of R, K, N, D, Q, E, and H, and / or at most 60% of the amino acids in X are selected from the group consisting of R, K, N, D, Q, E, and H.

139. The method of claim 137 or 138, wherein Y is a portion of a mutant comprising the sequence of SEQ ID NO: 2, characterized in that 141. The method of any one of claims 137-140, wherein the total number of E or D in X is at least 8, and / or the total number of E or D in X is at most 15.

142. The method of any one of claims 137-141, wherein the total number of R, K, T, A, N, Q, D, E, S, and G in X is greater than 30, and / or the total number of W, Y, F, M, L, I, and V in X is no more than 20.

143. The method of any one of claims 137-142, wherein Y comprises 15 to 25 amino acids, Y comprises 18 to 25 amino acids, or Y comprises 20 to 25 amino acids.

144. The method of any one of claims 137-143, wherein 40-65% of the amino acids in Y are selected from the group consisting of I, V, L, F, C, M, and A. ​ ​ 145. The method of any one of claims 137-144, wherein the total number of R, K, T, A, N, Q, D, E, S, and G in Y is no more than 10, and / or the total number of W, Y, F, M, L, I, and V in Y is no more than 15.

146. The method of any one of claims 137-145, wherein X comprises a sequence that is at least 80% identical to SEQ ID NO: 96, X comprises the sequence of SEQ ID NO: 96, or X is the sequence of SEQ ID NO:

96.

147. The method of any one of claims 137-146, wherein Y comprises a sequence that is at least 80% identical to any one selected from the group consisting of SEQ ID NOs: 97-103, Y comprises any one sequence selected from the group consisting of SEQ ID NOs: 97-103, or Y is any one sequence selected from the group consisting of SEQ ID NOs: 97-103.

148. The method of any one of claims 137-147, wherein the artificial polypeptide comprises a sequence that is at least 80% identical to any one selected from the group consisting of SEQ ID NOs: 104-110, the artificial polypeptide comprises any one sequence selected from the group consisting of SEQ ID NOs: 104-110, or the artificial polypeptide is any one sequence selected from the group consisting of SEQ ID NOs: 104-110.

149. The method of any one of claims 137-148, wherein the allergic conjunctivitis is at least one selected from the group consisting of seasonal allergic conjunctivitis, perennial allergic conjunctivitis, vernal keratoconjunctivitis, giant papillary conjunctivitis, atopic keratoconjunctivitis, and bullous keratoconjunctivitis.

150. The method of claim 149, wherein the seasonal allergic conjunctivitis is caused by or is partially caused by a seasonal allergen.

151. The method of claim 150, wherein the seasonal allergen is at least one selected from the group consisting of tree pollen, weed pollen, grass pollen, and mold spores.

152. The method of claim 149, wherein the perennial allergic conjunctivitis is caused by or is partially caused by a perennial allergen.

153. The method of claim 152, wherein the perennial allergen is at least one selected from the group consisting of dust mites, cockroaches, and animal dander.

154. The method of claim 149, wherein the vernal keratoconjunctivitis is at least one selected from the group consisting of eyelid vernal keratoconjunctivitis, limbal vernal keratoconjunctivitis, and mixed vernal keratoconjunctivitis.

155. The method of claim 149, wherein the giant papillary conjunctivitis is caused by or is partially caused by repeated mechanical irritation of the conjunctiva.

156. The method of claim 155, wherein the repeated mechanical irritation of the conjunctiva is associated with at least one selected from the group consisting of wearing of contact lenses, use of ocular prosthesis, use of conjunctival sutures, use of prominent scleral buckling, and corneal scar elevation.

157. The method of claim 149, wherein the atopic keratoconjunctivitis is accompanied by atopic dermatitis and / or asthma.

158. The method of claim 149, wherein the vesicular keratoconjunctivitis is caused by or partially caused by a delayed hypersensitivity reaction or inflammatory reaction of the cornea and conjunctiva to antigens expressed by various pathogens.

159. The method of claim 158, wherein the pathogen is at least one selected from bacteria (e.g., Staphylococcus aureus, Streptococcus viridans, Mycobacterium tuberculosis), viruses (e.g., Herpes simplex virus), chlamydia, fungi (e.g., Candida such as Candida albicans), and parasites (e.g., tapeworms such as Hymenolepis nana; and nematodes).

160. The method of any one of claims 137-159, wherein the subject does not have any ocular disease selected from viral conjunctivitis, bacterial conjunctivitis, chemical conjunctivitis, and dry eye or dry eye related conditions.

161. The method of any one of claims 137-160, wherein the subject experiences at least one symptom selected from conjunctival redness, conjunctival edema, conjunctival hyperemia, eyelid redness, eyelid edema, eyelid hyperemia, ocular itch, corneal visible lesions, mucous discharge, watery discharge, tearing, photophobia, foreign body sensation, and difficulty opening the eye prior to administration of the artificial polypeptide of formula (VII).

162. The method of any one of claims 137-161, wherein the subject shows a reduction in at least one symptom selected from conjunctival redness, conjunctival edema, conjunctival hyperemia, eyelid redness, eyelid edema, eyelid hyperemia, ocular itch, corneal visible lesions, mucous discharge, watery discharge, tearing, photophobia, foreign body sensation, and difficulty opening the eye after administration of at least one dose of the artificial polypeptide of formula (VII).

163. The method of any one of claims 137-162, wherein the subject shows an improvement in at least one tissue selected from conjunctiva, cornea, anterior chamber, iris, pupil, vitreous, and fundus after administration of at least one dose of the artificial polypeptide of formula (VII).

164. A method for treating or preventing allergic conjunctivitis in a subject in need thereof, comprising administering to the subject an effective amount of a mutant of the artificial polypeptide of formula (I), X-Y (I), wherein X is a moiety comprising a sequence that is at least 80% identical to SEQ ID NO: 1, Y is a moiety comprising 10 to 50 amino acids, at least 50% of which are selected from I, V, L, F, C, M, and A, Y comprises a total number of cysteines (C) that is less than 5, the mutant has at least 1, 2, 3, 4, 5, 6, 7, 8, or 9 of the D in X mutated to S, and / or at least 1, 2, 3, 4, 5, or 6 of the E in X mutated to T. ​ ​ ​ ​ characterized in that ​ 165. The method of claim 164, wherein at least 20% of the amino acids in X are selected from R, K, N, D, Q, E, and H, at least 30% of the amino acids in X are selected from R, K, N, D, Q, E, and H, at most 90% of the amino acids in X are selected from R, K, N, D, Q, E, and H, and / or at most 80% of the amino acids in X are selected from R, K, N, D, Q, E, and H.

166. The method of claim 164 or 165, wherein X comprises a sequence that is at least 70% identical to SEQ ID NO:

1.

167. The method of any one of claims 164-166, wherein Y comprises a total number of cysteines (C) that is less than 4, or Y comprises a total number of cysteines (C) that is less than 3.

168. The method of any one of claims 164-167, wherein Y comprises a total number of hydrophobic amino acids that is greater than 8, a total number of hydrophobic amino acids that is greater than 12, a total number of hydrophobic amino acids that is greater than 15, and / or a total number of hydrophilic amino acids that is no more than 5.

169. The method of any one of claims 164-168, wherein Y comprises a sequence that is at least 90% identical to any one selected from the group consisting of SEQ ID NOs: 3-15, 58-61, and 84-85, or Y comprises a sequence that is at least 90% identical to any one selected from the group consisting of SEQ ID NOs: 3-18, 58-61, and 84-85.

170. The method of any one of claims 164-169, wherein the allergic conjunctivitis is at least one selected from the group consisting of seasonal allergic conjunctivitis, perennial allergic conjunctivitis, vernal keratoconjunctivitis, giant papillary conjunctivitis, atopic keratoconjunctivitis, and bullous keratoconjunctivitis.

171. The method of claim 170, wherein the seasonal allergic conjunctivitis is caused by or is partially caused by a seasonal allergen.

172. The method of claim 171, wherein the seasonal allergen is at least one selected from the group consisting of tree pollen, weed pollen, grass pollen, and mold spores.

173. The method of claim 170, wherein the perennial allergic conjunctivitis is caused by or is partially caused by a perennial allergen.

174. The method of claim 173, wherein the perennial allergen is at least one selected from the group consisting of dust mites, cockroaches, and animal dander.

175. The method of claim 170, wherein the vernal keratoconjunctivitis is at least one selected from the group consisting of eyelid vernal keratoconjunctivitis, limbal vernal keratoconjunctivitis, and mixed vernal keratoconjunctivitis.

176. The method of claim 170, wherein the giant papillary conjunctivitis is caused by or is partially caused by repeated mechanical irritation of the conjunctiva.

177. The method of claim 176, wherein the repeated mechanical irritation of the conjunctiva is associated with at least one selected from the group consisting of contact lens wear, use of ocular prosthesis, use of conjunctival sutures, use of prominent scleral buckling, and corneal scarring.

178. The method of claim 170, wherein the atopic keratoconjunctivitis is accompanied by atopic dermatitis and / or asthma.

179. The method of claim 170, wherein the vesicular keratoconjunctivitis is caused by or partially caused by a delayed hypersensitivity reaction or inflammatory reaction of the cornea and conjunctiva to antigens expressed by various pathogens.

180. The method of claim 179, wherein the pathogen is at least one selected from bacteria (e.g., Staphylococcus aureus, Streptococcus viridans, Mycobacterium tuberculosis), viruses (e.g., Herpes simplex virus), chlamydia, fungi (e.g., Candida such as Candida albicans), and parasites (e.g., tapeworms such as Hymenolepis nana; and nematodes).

181. The method of any one of claims 164-180, wherein the subject does not have any ocular disease selected from viral conjunctivitis, bacterial conjunctivitis, chemical conjunctivitis, and dry eye or dry eye related conditions.

182. The method of any one of claims 164-181, wherein the subject experiences at least one symptom selected from conjunctival redness, conjunctival edema, conjunctival hyperemia, eyelid redness, eyelid edema, eyelid hyperemia, ocular itch, corneal visible lesions, mucous discharge, watery discharge, tearing, photophobia, foreign body sensation, and difficulty opening the eye prior to administration of the mutant of the artificial polypeptide of Formula (I).

183. The method of any one of claims 164-182, wherein the subject exhibits a reduction in at least one symptom selected from conjunctival redness, conjunctival edema, conjunctival hyperemia, eyelid redness, eyelid edema, eyelid hyperemia, ocular itch, corneal visible lesions, mucous discharge, watery discharge, tearing, photophobia, foreign body sensation, and difficulty opening the eye after administration of at least one dose of the mutant of the artificial polypeptide of Formula (I).

184. The method of any one of claims 164-183, wherein the subject exhibits an improvement in at least one tissue selected from conjunctiva, cornea, anterior chamber, iris, pupil, vitreous, and fundus after administration of at least one dose of the mutant of the artificial polypeptide of Formula (I).

185. A method for treating or preventing allergic conjunctivitis in a subject in need thereof, comprising administering to the subject an effective amount of a mutant of the artificial polypeptide of Formula (II), X-Y (II), wherein X is a moiety comprising a sequence that is at least 80% identical to SEQ ID NO: 1, Y is a moiety comprising 10 to 50 amino acids, at least 50% of which are selected from I, V, L, F, C, M, and A, Y comprises a sequence that is at most 90% identical to SEQ ID NO: 2, the mutant mutates at least 1, 2, 3, 4, 5, 6, 7, 8, or 9 Ds in X to S, and / or at least 1, 2, 3, 4, 5, or 6 Es in X to T. characterized in that ​ 186. The method of claim 185, wherein at least 20% of the amino acids in X are selected from R, K, N, D, Q, E, and H, at least 30% of the amino acids in X are selected from R, K, N, D, Q, E, and H, at most 90% of the amino acids in X are selected from R, K, N, D, Q, E, and H, and / or at most 80% of the amino acids in X are selected from R, K, N, D, Q, E, and H.

187. The method of claim 185 or 186, wherein X comprises a sequence that is at least 70% identical to SEQ ID NO:

1.

188. The method of any one of claims 185-187, wherein Y comprises a sequence that is at most 80% identical to SEQ ID NO: 2, or Y comprises a sequence that is at most 70% identical to SEQ ID NO:

2.

189. The method of any one of claims 185-188, wherein the total number of hydrophobic amino acids in Y is greater than 8, the total number of hydrophobic amino acids in Y is greater than 12, the total number of hydrophobic amino acids in Y is greater than 15, and / or the total number of hydrophilic amino acids in Y is no more than 5.

190. The method of any one of claims 185-189, wherein Y comprises a sequence that is at least 90% identical to any one selected from SEQ ID NOs: 16-18, or Y comprises a sequence that is at least 95% identical to any one selected from SEQ ID NOs: 16-18.

191. The method of any one of claims 185-190, wherein the allergic conjunctivitis is at least one selected from seasonal allergic conjunctivitis, perennial allergic conjunctivitis, vernal keratoconjunctivitis, giant papillary conjunctivitis, atopic keratoconjunctivitis, and vesicular keratoconjunctivitis.

192. The method of claim 191, wherein the seasonal allergic conjunctivitis is caused by or is partially caused by a seasonal allergen.

193. The method of claim 192, wherein the seasonal allergen is at least one selected from tree pollen, weed pollen, grass pollen, and mold spores.

194. The method of claim 191, wherein the perennial allergic conjunctivitis is caused by or is partially caused by a perennial allergen.

195. The method of claim 194, wherein the perennial allergen is at least one selected from dust mites, cockroaches, and animal dander.

196. The method of claim 191, wherein the vernal keratoconjunctivitis is at least one selected from eyelid vernal keratoconjunctivitis, limbal vernal keratoconjunctivitis, and mixed vernal keratoconjunctivitis.

197. The method of claim 191, wherein the giant papillary conjunctivitis is caused by or is partially caused by repeated mechanical irritation of the conjunctiva.

198. The method of claim 197, wherein the repeated mechanical irritation of the conjunctiva is associated with at least one selected from the group consisting of contact lens wear, use of ocular prosthesis, use of conjunctival sutures, use of prominent scleral buckling, and corneal scarring.

199. The method of claim 191, wherein the atopic keratoconjunctivitis is accompanied by atopic dermatitis and / or asthma.

200. The method of claim 191, wherein the vesicular keratoconjunctivitis is caused by or partially caused by a delayed-type hypersensitivity or inflammatory response of the cornea and conjunctiva to antigens expressed by various pathogens.

201. The method of claim 200, wherein the pathogen is at least one selected from bacteria (e.g., Staphylococcus aureus, Streptococcus viridans, Mycobacterium tuberculosis), viruses (e.g., Herpes simplex virus), chlamydia, fungi (e.g., Candida such as Candida albicans), and parasites (e.g., tapeworms such as Hymenolepis microstoma; and nematodes).

202. The method of any one of claims 185-201, wherein the subject does not have any ocular disease selected from viral conjunctivitis, bacterial conjunctivitis, chemical conjunctivitis, and dry eye or dry eye related disorders.

203. The method of any one of claims 185-202, wherein the subject experiences at least one symptom selected from conjunctival redness, conjunctival edema, conjunctival hyperemia, eyelid redness, eyelid edema, eyelid hyperemia, ocular itch, corneal visible lesions, mucous discharge, watery discharge, tearing, photophobia, foreign body sensation, and difficulty opening the eye prior to administration of the mutant of the artificial polypeptide of Formula (II).

204. The method of any one of claims 185-203, wherein the subject exhibits a reduction in at least one symptom selected from conjunctival redness, conjunctival edema, conjunctival hyperemia, eyelid redness, eyelid edema, eyelid hyperemia, ocular itch, corneal visible lesions, mucous discharge, watery discharge, tearing, photophobia, foreign body sensation, and difficulty opening the eye after administration of at least one dose of the mutant of the artificial polypeptide of Formula (II).

205. The method of any one of claims 185-204, wherein the subject exhibits an improvement in at least one tissue selected from conjunctiva, cornea, anterior chamber, iris, pupil, vitreous, and fundus after administration of at least one dose of the mutant of the artificial polypeptide of Formula (II).

206. A method for treating or preventing allergic conjunctivitis in a subject in need thereof, comprising administering to the subject an effective amount of a mutant of the artificial polypeptide of Formula (III), X-Y (III), wherein X is a moiety comprising 40 to 65 amino acids, at least 50% of which are selected from H, R, K, D, Q, N, and E, Y is a moiety comprising a sequence that is at least 80% identical to SEQ ID NO: 2, the total number of H, R, K, D, Q, N, and E in X is less than 33, the mutant has at least one D in X mutated to S, and / or at least one E in X mutated to T.

207. The method of claim 206, wherein the subject does not have any ocular disease selected from viral conjunctivitis, bacterial conjunctivitis, chemical conjunctivitis, and dry eye or dry eye related disorders.

208. The method of claim 206, wherein the subject experiences at least one symptom selected from conjunctival redness, conjunctival edema, conjunctival hyperemia, eyelid redness, eyelid edema, eyelid hyperemia, ocular itch, corneal visible lesions, mucous discharge, watery discharge, tearing, photophobia, foreign body sensation, and difficulty opening the eye prior to administration of the mutant of the artificial polypeptide of Formula (III).

209. The method of claim 206, wherein the subject exhibits a reduction in at least one symptom selected from conjunctival redness, conjunctival edema, conjunctival hyperemia, eyelid redness, eyelid edema, eyelid hyperemia, ocular itch, corneal visible lesions, mucous discharge, watery discharge, tearing, photophobia, foreign body sensation, and difficulty opening the eye after administration of at least one dose of the mutant of the artificial polypeptide of Formula (III). characterized in that 210. The method of claim 206, wherein the subject exhibits an improvement in at least one tissue selected from conjunctiva, cornea, anterior chamber, iris, pupil, vitreous, and fundus after administration of at least one dose of the mutant of the artificial polypeptide of Formula (III).

207. The method of claim 206, wherein at least 20% of the amino acids in X are selected from R, K, N, D, Q, E, and H, at least 30% of the amino acids in X are selected from R, K, N, D, Q, E, and H, at most 90% of the amino acids in X are selected from R, K, N, D, Q, E, and H, and / or at most 80% of the amino acids in X are selected from R, K, N, D, Q, E, and H.

208. The method of claim 206 or 207, wherein X comprises a sequence that is at least 70% identical to SEQ ID NO:

1.

209. The method of any one of claims 206-208, wherein Y comprises a sequence that is at least 90% identical to SEQ ID NO: 2, or Y comprises the sequence of SEQ ID NO:

2.

210. The method of any one of claims 206-209, wherein at least 50% of the amino acids in Y are selected from I, V, L, F, C, M, and A.

211. The method of any one of claims 206-210, wherein the total number of H, R, K, D, Q, N, and E in X is less than 30, the total number of H, R, K, D, Q, N, and E in X is less than 25, or the total number of H, R, K, D, Q, N, and E in X is less than 20.

212. The method of any one of claims 206-211, wherein the total number of hydrophilic amino acids in X is greater than 10, the total number of hydrophilic amino acids in X is greater than 15, the total number of hydrophilic amino acids in X is greater than 20, the total number of hydrophilic amino acids in X is greater than 25, the total number of hydrophobic amino acids in X is no more than 15, and / or the total number of hydrophobic amino acids in X is no more than 10.

213. The method of any one of claims 206-212, wherein the allergic conjunctivitis is at least one selected from seasonal allergic conjunctivitis, perennial allergic conjunctivitis, vernal keratoconjunctivitis, giant papillary conjunctivitis, atopic keratoconjunctivitis, and bullous keratoconjunctivitis.

214. The method of claim 213, wherein the seasonal allergic conjunctivitis is caused by or is partially caused by a seasonal allergen.

215. The method of claim 214, wherein the seasonal allergen is at least one selected from tree pollen, weed pollen, grass pollen, and mold spores.

216. The method of claim 213, wherein the perennial allergic conjunctivitis is caused by or is partially caused by a perennial allergen.

217. The method of claim 216, wherein the perennial allergen is at least one selected from dust mites, cockroaches, and animal dander.

218. The method of claim 213, wherein the vernal keratoconjunctivitis is at least one selected from lid vernal keratoconjunctivitis, limbal vernal keratoconjunctivitis, and mixed vernal keratoconjunctivitis.

219. The method of claim 213, wherein the giant papillary conjunctivitis is caused by or is partially caused by repeated mechanical irritation of the conjunctiva.

220. The method of claim 219, wherein the repeated mechanical stimulation of the conjunctiva is associated with at least one selected from the group consisting of contact lens wear, use of an ocular prosthesis, use of conjunctival sutures, use of prominent scleral banding, and pterygium scar elevation.

221. The method of claim 213, wherein the atopic keratoconjunctivitis is accompanied by atopic dermatitis and / or asthma.

222. The method of claim 213, wherein the vesicular keratoconjunctivitis is caused by or partially caused by a delayed hypersensitivity reaction or inflammatory reaction of the cornea and conjunctiva to antigens expressed by various pathogens.

223. The method of claim 222, wherein the pathogen is at least one selected from the group consisting of bacteria (e.g., Staphylococcus aureus, Streptococcus viridans, Mycobacterium tuberculosis), viruses (e.g., herpes simplex virus), chlamydia, fungi (e.g., Candida such as Candida albicans), and parasites (e.g., tapeworms such as Hymenolepis microstoma; and nematodes).

224. The method of any one of claims 206-223, wherein the subject does not have any ocular disease selected from the group consisting of viral conjunctivitis, bacterial conjunctivitis, chemical conjunctivitis, and dry eye or dry eye related conditions.

225. The method of any one of claims 206-224, wherein the subject experiences at least one symptom selected from the group consisting of conjunctival redness, conjunctival edema, conjunctival hyperemia, eyelid redness, eyelid edema, eyelid hyperemia, ocular itch, corneal visible lesions, mucous discharge, watery discharge, tearing, photophobia, foreign body sensation, and difficulty opening the eye prior to administration of the mutant of the artificial polypeptide of Formula (III).

226. The method of any one of claims 206-225, wherein the subject exhibits a reduction in at least one symptom selected from the group consisting of conjunctival redness, conjunctival edema, conjunctival hyperemia, eyelid redness, eyelid edema, eyelid hyperemia, ocular itch, corneal visible lesions, mucous discharge, watery discharge, tearing, photophobia, foreign body sensation, and difficulty opening the eye after administration of at least one dose of the mutant of the artificial polypeptide of Formula (III).

227. The method of any one of claims 206-226, wherein the subject exhibits an improvement in at least one tissue selected from the group consisting of conjunctiva, cornea, anterior chamber, iris, pupil, vitreous, and fundus after administration of at least one dose of the mutant of the artificial polypeptide of Formula (III).

228. A method for treating or preventing allergic conjunctivitis in a subject in need thereof, comprising administering to the subject an effective amount of a mutant of the artificial polypeptide of Formula (IV), X-Y (IV), wherein X is a moiety comprising 40 to 65 amino acids, at least 50% of the amino acids being selected from the group consisting of H, R, K, D, Q, N, and E, Y is a moiety comprising a sequence that is at least 80% identical to SEQ ID NO: 2, X comprises a sequence that is at most 90% identical to SEQ ID NO: 1, and Y comprises a sequence that is at most 90% identical to SEQ ID NO:

2. ​ ​ ​ characterized in that The mutant has at least 1, 2, 3, 4, 5, 6, 7, 8, or 9 D in X mutated to S, and / or at least 1, 2, 3, 4, 5, or 6 E in X mutated to T.

229. The method of claim 228, wherein at least 20% of the amino acids in X are selected from the group consisting of R, K, N, D, Q, E, and H, at least 30% of the amino acids in X are selected from the group consisting of R, K, N, D, Q, E, and H, at most 90% of the amino acids in X are selected from the group consisting of R, K, N, D, Q, E, and H, and / or at most 80% of the amino acids in X are selected from the group consisting of R, K, N, D, Q, E, and H.

230. The method of claim 228 or 229, wherein X comprises a sequence that is at least 70% identical to SEQ ID NO:

1.

231. The method of any one of claims 228-230, wherein Y comprises a sequence that is at least 90% identical to SEQ ID NO: 2, or Y comprises the sequence of SEQ ID NO:

2.

232. The method of any one of claims 228-231, wherein at least 50% of the amino acids in Y are selected from the group consisting of I, V, L, F, C, M, and A.

233. The method of any one of claims 228-232, wherein the total number of hydrophilic amino acids in X is greater than 10, the total number of hydrophilic amino acids in X is greater than 15, the total number of hydrophilic amino acids in X is greater than 20, the total number of hydrophilic amino acids in X is greater than 25, the total number of hydrophobic amino acids in X is no more than 15, and / or the total number of hydrophobic amino acids in X is no more than 10.

234. The method of any one of claims 228-233, wherein the allergic conjunctivitis is at least one selected from the group consisting of seasonal allergic conjunctivitis, perennial allergic conjunctivitis, vernal keratoconjunctivitis, giant papillary conjunctivitis, atopic keratoconjunctivitis, and bullous keratoconjunctivitis.

235. The method of claim 234, wherein the seasonal allergic conjunctivitis is caused by or is partially caused by a seasonal allergen.

236. The method of claim 235, wherein the seasonal allergen is at least one selected from the group consisting of tree pollen, weed pollen, grass pollen, and mold spores.

237. The method of claim 234, wherein the perennial allergic conjunctivitis is caused by or is partially caused by a perennial allergen.

238. The method of claim 237, wherein the perennial allergen is at least one selected from the group consisting of dust mites, cockroaches, and animal dander.

239. The method of claim 234, wherein the vernal keratoconjunctivitis is at least one selected from the group consisting of eyelid vernal keratoconjunctivitis, limbal vernal keratoconjunctivitis, and mixed vernal keratoconjunctivitis.

240. The method of claim 234, wherein the giant papillary conjunctivitis is caused by or is partially caused by repeated mechanical irritation of the conjunctiva.

241. The method of claim 240, wherein the repeated mechanical stimulation of the conjunctiva is associated with at least one selected from the group consisting of contact lens wear, use of an ocular prosthesis, use of conjunctival sutures, use of prominent scleral banding, and corneal scar elevation.

242. The method of claim 234, wherein the atopic keratoconjunctivitis is accompanied by atopic dermatitis and / or asthma.

243. The method of claim 234, wherein the vesicular keratoconjunctivitis is caused by or partially caused by a delayed hypersensitivity reaction or inflammatory reaction of the cornea and conjunctiva to antigens expressed by various pathogens.

244. The method of claim 243, wherein the pathogen is at least one selected from the group consisting of bacteria (e.g., Staphylococcus aureus, Streptococcus viridans, Mycobacterium tuberculosis), viruses (e.g., herpes simplex virus), chlamydia, fungi (e.g., Candida such as Candida albicans), and parasites (e.g., tapeworms such as Hymenolepis microstoma; and nematodes).

245. The method of any one of claims 228-244, wherein the subject does not have any ocular disease selected from the group consisting of viral conjunctivitis, bacterial conjunctivitis, chemical conjunctivitis, and dry eye or dry eye related conditions.

246. The method of any one of claims 228-245, wherein the subject experiences at least one symptom selected from the group consisting of conjunctival redness, conjunctival edema, conjunctival hyperemia, eyelid redness, eyelid edema, eyelid hyperemia, ocular itch, corneal visible lesions, mucous discharge, watery discharge, tearing, photophobia, foreign body sensation, and difficulty opening the eye prior to administration of the mutant of the artificial polypeptide of Formula (IV).

247. The method of any one of claims 228-246, wherein the subject exhibits a reduction in at least one symptom selected from the group consisting of conjunctival redness, conjunctival edema, conjunctival hyperemia, eyelid redness, eyelid edema, eyelid hyperemia, ocular itch, corneal visible lesions, mucous discharge, watery discharge, tearing, photophobia, foreign body sensation, and difficulty opening the eye following administration of at least one dose of the mutant of the artificial polypeptide of Formula (IV).

248. The method of any one of claims 228-247, wherein the subject exhibits an improvement in at least one tissue selected from the group consisting of conjunctiva, cornea, anterior chamber, iris, pupil, vitreous, and fundus following administration of at least one dose of the mutant of the artificial polypeptide of Formula (IV).

249. A method for treating or preventing allergic conjunctivitis in a subject in need thereof, comprising administering to the subject an effective amount of a mutant of the artificial polypeptide of Formula (V), X-Y (V), wherein X is a moiety comprising a sequence that is at least 80% identical to SEQ ID NO: 1, Y is a moiety comprising 10 to 30 amino acids, wherein Y comprises a sequence having at least 10 contiguous AAs of SEQ ID NO: 2, characterized in that the mutant mutates at least 1, 2, 3, 4, 5, 6, 7, 8, or 9 of the D in X to S, and / or at least 1, 2, 3, 4, 5, or 6 of the E in X to T.

250. The method of claim 249, wherein at least 20% of the amino acids in X are selected from R, K, N, D, Q, E, and H, at least 30% of the amino acids in X are selected from R, K, N, D, Q, E, and H, at most 90% of the amino acids in X are selected from R, K, N, D, Q, E, and H, and / or at most 80% of the amino acids in X are selected from R, K, N, D, Q, E, and H.

251. The method of claim 249 or 250, wherein Y comprises 10 to 25 amino acids, Y comprises 10 to 20 amino acids, or Y comprises 10 to 15 amino acids.

252. The method of any one of claims 249 to 251, wherein X comprises a sequence that is at least 70% identical to SEQ ID NO:

1.

253. The method of any one of claims 249 to 252, wherein Y comprises a sequence that is at most 80% identical to SEQ ID NO: 2, Y comprises a sequence that is at most 70% identical to SEQ ID NO: 2, or Y comprises a sequence that is at most 50% identical to SEQ ID NO:

2.

254. The method of any one of claims 249 to 253, wherein the allergic conjunctivitis is at least one selected from seasonal allergic conjunctivitis, perennial allergic conjunctivitis, vernal keratoconjunctivitis, giant papillary conjunctivitis, atopic keratoconjunctivitis, and vesicular keratoconjunctivitis.

255. The method of claim 254, wherein the seasonal allergic conjunctivitis is caused by or is partially caused by a seasonal allergen.

256. The method of claim 255, wherein the seasonal allergen is at least one selected from tree pollen, weed pollen, grass pollen, and mold spores.

257. The method of claim 254, wherein the perennial allergic conjunctivitis is caused by or is partially caused by a perennial allergen.

258. The method of claim 257, wherein the perennial allergen is at least one selected from dust mites, cockroaches, and animal dander.

259. The method of claim 254, wherein the vernal keratoconjunctivitis is at least one selected from eyelid vernal keratoconjunctivitis, limbal vernal keratoconjunctivitis, and mixed vernal keratoconjunctivitis.

260. The method of claim 254, wherein the giant papillary conjunctivitis is caused by or is partially caused by repeated mechanical irritation of the conjunctiva.

261. The method of claim 260, wherein the repeated mechanical irritation of the conjunctiva is associated with at least one selected from the group consisting of contact lens wear, use of ocular prosthesis, use of conjunctival sutures, use of prominent scleral buckling, and corneal scar elevation.

262. The method of claim 254, wherein the atopic keratoconjunctivitis is accompanied by atopic dermatitis and / or asthma.

263. The method of claim 254, wherein the vesicular keratoconjunctivitis is caused by or is partially caused by a delayed hypersensitivity reaction or an inflammatory reaction of the cornea and conjunctiva to antigens expressed by various pathogens.

264. The method of claim 263, wherein the pathogen is at least one selected from bacteria (e.g., Staphylococcus aureus, Streptococcus viridans, Mycobacterium tuberculosis), viruses (e.g., Herpes simplex virus), chlamydia, fungi (e.g., Candida, such as Candida albicans), and parasites (e.g., tapeworms, such as Hymenolepis microstoma; and nematodes).

265. The method of any one of claims 249-264, wherein the subject does not have any ocular disease selected from viral conjunctivitis, bacterial conjunctivitis, chemical conjunctivitis, and dry eye or dry eye related conditions.

266. The method of any one of claims 249-265, wherein the subject experiences at least one symptom selected from conjunctival redness, conjunctival edema, conjunctival hyperemia, eyelid redness, eyelid edema, eyelid hyperemia, ocular itch, corneal visible lesions, mucous discharge, watery discharge, tearing, photophobia, foreign body sensation, and difficulty opening the eye prior to administration of the mutant of the artificial polypeptide of Formula (V).

267. The method of any one of claims 249-266, wherein the subject exhibits a reduction in at least one symptom selected from conjunctival redness, conjunctival edema, conjunctival hyperemia, eyelid redness, eyelid edema, eyelid hyperemia, ocular itch, corneal visible lesions, mucous discharge, watery discharge, tearing, photophobia, foreign body sensation, and difficulty opening the eye after administration of at least one dose of the mutant of the artificial polypeptide of Formula (V).

268. The method of any one of claims 249-267, wherein the subject exhibits an improvement in at least one tissue selected from conjunctiva, cornea, anterior chamber, iris, pupil, vitreous, and fundus after administration of at least one dose of the mutant of the artificial polypeptide of Formula (V).

269. A method for treating or preventing allergic conjunctivitis in a subject in need thereof, comprising administering to the subject an effective amount of a polypeptide having at least 70% identity to any one selected from the group consisting of SEQ ID NO: 28, SEQ ID NO: 57, and 62-74, or a fragment or variant thereof.

270. The method of claim 269, wherein the polypeptide is a polypeptide of any one of SEQ ID NO: 28, SEQ ID NO: 57, and 62-74, or a fragment or variant thereof, the polypeptide is a polypeptide of any one of SEQ ID NO: 28, SEQ ID NO: 57, and 62-74, the polypeptide is a polypeptide of any one of SEQ ID NO: 28 and 62-74, or the polypeptide is a polypeptide of SEQ ID NO:

28.

271. The method of claim 269 or 270, wherein the allergic conjunctivitis is at least one selected from seasonal allergic conjunctivitis, perennial allergic conjunctivitis, vernal keratoconjunctivitis, giant papillary conjunctivitis, atopic keratoconjunctivitis, and vesicular keratoconjunctivitis.

272. The method of claim 271, wherein the seasonal allergic conjunctivitis is caused by or partially caused by a seasonal allergen.

273. The method of claim 272, wherein the seasonal allergen is at least one selected from the group consisting of tree pollen, weed pollen, grass pollen, and mold spores.

274. The method of claim 271, wherein the perennial allergic conjunctivitis is caused by or partially caused by a perennial allergen.

275. The method of claim 274, wherein the perennial allergen is at least one selected from the group consisting of dust mites, cockroaches, and animal dander.

276. The method of claim 271, wherein the vernal keratoconjunctivitis is at least one selected from the group consisting of lid vernal keratoconjunctivitis, limbal vernal keratoconjunctivitis, and mixed vernal keratoconjunctivitis.

277. The method of claim 271, wherein the giant papillary conjunctivitis is caused by or partially caused by repeated mechanical irritation of the conjunctiva.

278. The method of claim 277, wherein the repeated mechanical irritation of the conjunctiva is associated with at least one selected from the group consisting of contact lens wear, use of ocular prosthesis, use of conjunctival sutures, use of prominent scleral buckling, and corneal scar elevation.

279. The method of claim 271, wherein the atopic keratoconjunctivitis is accompanied by atopic dermatitis and / or asthma.

280. The method of claim 271, wherein the vesicular keratoconjunctivitis is caused by or partially caused by a delayed hypersensitivity or inflammatory response of the cornea and conjunctiva to antigens expressed by various pathogens.

281. The method of claim 280, wherein the pathogen is at least one selected from the group consisting of bacteria (e.g., Staphylococcus aureus, Streptococcus viridans, Mycobacterium tuberculosis), viruses (e.g., Herpes simplex virus), chlamydia, fungi (e.g., Candida such as Candida albicans), and parasites (e.g., tapeworms such as Hymenolepis microstoma; and nematodes).

282. The method of any one of claims 269-281, wherein the subject does not have any ocular disease selected from the group consisting of viral conjunctivitis, bacterial conjunctivitis, chemical conjunctivitis, and dry eye or dry eye related disorders.

283. The method of any one of claims 269-282, wherein the subject experiences at least one symptom selected from the group consisting of conjunctival redness, conjunctival edema, conjunctival hyperemia, eyelid redness, eyelid edema, eyelid hyperemia, ocular itch, corneal visible lesions, mucous discharge, watery discharge, tearing, photophobia, foreign body sensation, and difficulty opening the eye prior to administration of the polypeptide or fragment or variant thereof having at least 70% identity to any one selected from the group consisting of SEQ ID NO: 28, SEQ ID NO: 57, and 62-74.

284. The method of any one of claims 269-283, wherein the subject exhibits a reduction in at least one symptom selected from the group consisting of conjunctival redness, conjunctival edema, conjunctival hyperemia, eyelid redness, eyelid edema, eyelid hyperemia, ocular itch, corneal visible lesions, mucous discharge, watery discharge, tearing, photophobia, foreign body sensation, and difficulty opening the eye after administration of at least one dose of the polypeptide or fragment or variant thereof having at least 70% identity to any one selected from the group consisting of SEQ ID NO: 28, SEQ ID NO: 57, and 62-74.

285. The method of any one of claims 269-284, wherein the subject exhibits an improvement in at least one tissue selected from the group consisting of conjunctiva, cornea, anterior chamber, iris, pupil, vitreous, and fundus after administration of at least one dose of the polypeptide or fragment or variant thereof having at least 70% identity to any one selected from the group consisting of SEQ ID NO: 28, SEQ ID NO: 57, and 62-74.

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