Use of polypeptides for the prevention or treatment of allergic conjunctivitis

Abstract

Polypeptides for the prevention or treatment of allergic conjunctivitis are provided. 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 one of the polypeptides. The present disclosure provides a new means for preventing or treating allergic conjunctivitis. Specifically, the present disclosure provides the use of polypeptides for the prevention or treatment of 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 one of the polypeptides disclosed herein.

Description

[Technical Field]

[0001] cross reference 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.

[0002] Technical Field The present disclosure provides the use of polypeptides for the prevention or treatment of 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 one of the polypeptides disclosed herein. [Background technology]

[0003] background 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 a small volume of mucus and tears, and also helps prevent the entry of microorganisms into the eye and contributes to immune surveillance. In particular, conjunctival disorders are common among different populations because the ocular surface is directly exposed to and easily affected by external influences.

[0004] Conjunctivitis (also called "pink eye"), a very common type of conjunctival disorder, is an ocular inflammation of the inner surface and outermost layer of the white part of the eyelid. Conjunctivitis is often manifested by symptoms such as redness and swelling of the conjunctiva and watering. This disorder can be caused by viral infection (i.e., viral conjunctivitis), bacterial infection (i.e., bacterial conjunctivitis), chemicals (i.e., chemical conjunctivitis), allergens (i.e., allergic conjunctivitis), or an autoimmune response (i.e., autoimmune conjunctivitis, e.g., Sjögren's syndrome, Stevens-Johnson syndrome, and cicatricial pemphigoid).

[0005] Allergic conjunctivitis, in particular, is the most frequent cause of conjunctivitis, reported to affect 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 class of inflammatory diseases caused by hypersensitivity of the conjunctiva to various allergen stimuli. This disorder is essentially an immune response of the conjunctiva to various indoor or outdoor allergens that enter the eye, such as pollen, mold spores, house dust mites, and pet dander. The eyes are easily affected by allergens because they are directly exposed to the external environment and are relatively sensitive to various irritants. The body responds to these allergens by releasing chemicals, including histamine, which cause inflammation and subsequently develop allergic conjunctivitis.

[0006] Although allergic conjunctivitis is not a contagious disorder and is not life-threatening, it can cause considerable inconvenience to the lives of patients affected by this disorder and can be quite difficult to manage.Some common signs and symptoms of allergic conjunctivitis include, among others, redness, swelling, or hyperemia of the conjunctiva, redness, swelling, or hyperemia of the eyelids, itchy eyes, visible damage to the cornea, mucous discharge, watery discharge, tearing, photophobia, foreign body sensation, and difficulty in opening the eyes.It has also been reported that patients may experience several other symptoms, such as nasal itching, sneezing, coughing, brief periods of blurred vision, distractibility, reduced productivity, and fatigue. The current clinical measures for treating allergic conjunctivitis include administering eye drops or other ophthalmic preparations containing antihistamines, mast cell stabilizers, glucocorticoids and / or immunosuppressants, which help reduce the signs and symptoms of allergic conjunctivitis.But these measures suffer from problems, such as slow onset, limited effectiveness and / or duration, induce ocular complications, low treatment compliance, inconsistent dosing and drug abuse.As such, there is still an unmet need in the medical community for a drug that can effectively alleviate or treat allergic conjunctivitis. [Prior art documents] [Non-patent literature]

[0007] [Non-Patent Document 1] Mourad MS, Rihan RA (April 2018) The Egyptian Journal of Hospital Medicine. 71 (2): 2484-2489 Summary of the Invention [Means for solving the problem]

[0008] overview The present disclosure provides a new means for preventing or treating allergic conjunctivitis. Specifically, the present disclosure provides the use of polypeptides for preventing or treating allergic conjunctivitis. Also provided is a method for treating or preventing allergic conjunctivitis in a subject in need of such treatment or prevention, comprising administering to the subject an effective amount of any one of the polypeptides disclosed herein.

[0009] In one embodiment, a method is provided for treating or preventing allergic conjunctivitis in a subject in need thereof, comprising administering an effective amount of an artificial polypeptide of formula (I): XY(I) administering to a subject: X is a portion containing a sequence having at least 80% identity with 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 contains a total number of cysteines (C) of less than 5.

[0010] In some embodiments, X comprises a sequence having at least 90% identity to SEQ ID NO:1, X comprises a sequence having at least 95% identity to 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 to SEQ ID NO:1. In some embodiments, X comprises a sequence having at least 95% identity to 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 of X are selected from R, K, N, D, Q, E, and H. In some embodiments, X comprises a sequence having at least 90% identity to any one selected from SEQ ID NOs:81-83.

[0011] In some embodiments, Y, comprises a total number of cysteines (C) less than 4, Y, comprises a total number of cysteines (C) less than 3, or Y, comprises a total number of cysteines (C) less than 2. In some embodiments, Y, comprises a total number of cysteines (C) less than 4. In some embodiments, Y, comprises a total number of cysteines (C) less than 3. In some embodiments, Y, comprises a total number of cysteines (C) less than 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 5 or less. 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, is 5 or less. In some embodiments, Y comprises a sequence having at least 90% identity to any one selected from SEQ ID NOs: 3-15, 58-61 and 84-85, or Y comprises a sequence having at least 90% identity to any one selected from SEQ ID NOs: 3-18, 58-61 and 84-85. In some embodiments, Y comprises a sequence having at least 90% identity to any one selected from SEQ ID NOs: 3-15, 58-61 and 84-85. In some embodiments, Y comprises a sequence having at least 90% identity to any one selected from SEQ ID NOs: 3-18, 58-61 and 84-85.

[0012] In some embodiments, the polypeptide comprises a sequence having at least 90% identity to any one selected from SEQ ID NOs: 29-41, 54-57, 75 and 91-95.

[0013] In some embodiments, 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 phlyctenular keratoconjunctivitis. In some embodiments, the seasonal allergic conjunctivitis is caused or partially caused by a seasonal allergen. In some embodiments, the seasonal allergen is at least one selected from the group consisting of tree pollen, weed pollen, grass pollen, and mold spores. In some embodiments, the perennial allergic conjunctivitis is caused or partially caused by a perennial allergen. In some embodiments, the perennial allergen is at least one selected from the group consisting of house dust mites, cockroaches, and animal dander. In some embodiments, the vernal keratoconjunctivitis is at least one selected from the group consisting of palpebral vernal keratoconjunctivitis, limbal vernal keratoconjunctivitis, and mixed vernal keratoconjunctivitis. In some embodiments, giant papillary conjunctivitis is caused or partially caused by repeated mechanical irritation of the conjunctiva. In some embodiments, 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 prostheses, use of conjunctival sutures, use of protruding scleral buckles, and raised corneal scars. In some embodiments, atopic keratoconjunctivitis is accompanied by atopic dermatitis and / or asthma. In some embodiments, phlyctenular keratoconjunctivitis is caused or partially caused 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 the group consisting of bacteria (e.g., Staphylococcus aureus, Streptococcus viridians, Mycobacterium tuberculosis), viruses (e.g., herpes simplex virus), chlamydia, fungi (e.g., Candida, e.g., Candida albicans), and parasites (e.g., tapeworms, e.g., Hymenolepis nana; and nematodes).In some embodiments, the subject does not have any ocular disease selected from the group consisting of viral conjunctivitis, bacterial conjunctivitis, chemical conjunctivitis, and dry eye or a dry eye-related disorder. In some embodiments, the subject experiences at least one symptom selected from the group consisting of conjunctival redness, conjunctival edema, conjunctival congestion, eyelid redness, eyelid edema, eyelid congestion, itchy eyes, visible corneal damage, mucous eye discharge, watery eye discharge, tearing, photophobia, foreign body sensation, and difficulty opening the eyes prior to administration of the artificial polypeptide of Formula (I). In some embodiments, the subject, after administration of at least one dose of the artificial polypeptide of Formula (I), exhibits a reduction in at least one symptom selected from the group consisting of conjunctival redness, conjunctival edema, conjunctival congestion, eyelid redness, eyelid edema, eyelid congestion, itchy eyes, visible corneal damage, mucous discharge, watery discharge, tearing, photophobia, foreign body sensation, and difficulty opening the eye. In some embodiments, the subject, after administration of at least one dose of the artificial polypeptide of Formula (I), exhibits an improvement in at least one tissue selected from the group consisting of the conjunctiva, cornea, anterior chamber, iris, pupil, vitreous, and fundus.

[0014] In another aspect, a method is provided for treating or preventing allergic conjunctivitis in a subject in need thereof, comprising administering an effective amount of an artificial polypeptide of formula (II): XY(II) administering to a subject: X is a portion containing a sequence having at least 80% identity with 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 having at most 90% identity to SEQ ID NO:2.

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

[0016] In some embodiments, Y comprises a sequence having at most 80% identity to SEQ ID NO:2, Y comprises a sequence having at most 70% identity to SEQ ID NO:2, or Y comprises a sequence having at most 50% identity to SEQ ID NO:2. In some embodiments, Y comprises a sequence having at most 80% identity to SEQ ID NO:2. In some embodiments, Y comprises a sequence having at most 70% identity to SEQ ID NO:2. In some embodiments, Y comprises a sequence having at most 50% identity to 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 5 or less. 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 is 5 or less. In some embodiments, Y comprises a sequence having at least 90% identity to any one selected from SEQ ID NOs: 16-18, or Y comprises a sequence having at least 95% identity to any one selected from SEQ ID NOs: 16-18. In some embodiments, Y comprises a sequence having at least 90% identity to any one selected from SEQ ID NOs: 16-18. In some embodiments, Y comprises a sequence having at least 95% identity to any one selected from SEQ ID NOs: 16-18.

[0017] In some embodiments, the polypeptide comprises a sequence having at least 90% identity to any one selected from SEQ ID NOs: 42-44.

[0018] In some embodiments, 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 phlyctenular keratoconjunctivitis. In some embodiments, the seasonal allergic conjunctivitis is caused or partially caused by a seasonal allergen. In some embodiments, the seasonal allergen is at least one selected from the group consisting of tree pollen, weed pollen, grass pollen, and mold spores. In some embodiments, the perennial allergic conjunctivitis is caused or partially caused by a perennial allergen. In some embodiments, the perennial allergen is at least one selected from the group consisting of house dust mites, cockroaches, and animal dander. In some embodiments, the vernal keratoconjunctivitis is at least one selected from the group consisting of palpebral vernal keratoconjunctivitis, limbal vernal keratoconjunctivitis, and mixed vernal keratoconjunctivitis. In some embodiments, giant papillary conjunctivitis is caused or partially caused by repeated mechanical irritation of the conjunctiva. In some embodiments, 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 prostheses, use of conjunctival sutures, use of protruding scleral buckles, and raised corneal scars. In some embodiments, atopic keratoconjunctivitis is accompanied by atopic dermatitis and / or asthma. In some embodiments, phlyctenular keratoconjunctivitis is caused or partially caused 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 the group consisting of bacteria (e.g., Staphylococcus aureus, Streptococcus viridians, Mycobacterium tuberculosis), viruses (e.g., herpes simplex virus), chlamydia, fungi (e.g., Candida, e.g., Candida albicans), and parasites (e.g., tapeworms, e.g., Hymenolepis nana; and nematodes).In some embodiments, the subject does not have any ocular disease selected from the group consisting of viral conjunctivitis, bacterial conjunctivitis, chemical conjunctivitis, and dry eye or a dry eye-related disorder. In some embodiments, the subject experiences at least one symptom selected from the group consisting of conjunctival redness, conjunctival edema, conjunctival congestion, eyelid redness, eyelid edema, eyelid congestion, itchy eyes, visible corneal damage, mucous eye discharge, watery eye discharge, tearing, photophobia, foreign body sensation, and difficulty opening the eyes prior to administration of the artificial polypeptide of Formula (II). In some embodiments, the subject, after administration of at least one dose of the artificial polypeptide of Formula (II), exhibits a reduction in at least one symptom selected from the group consisting of conjunctival redness, conjunctival edema, conjunctival congestion, eyelid redness, eyelid edema, eyelid congestion, itchy eyes, visible corneal damage, mucous eye discharge, watery eye discharge, tearing, photophobia, foreign body sensation, and difficulty opening the eye. In some embodiments, the subject, after administration of at least one dose of the artificial polypeptide of Formula (II), exhibits an improvement in at least one tissue selected from the group consisting of the conjunctiva, cornea, anterior chamber, iris, pupil, vitreous, and fundus.

[0019] In another aspect, a method is provided for treating or preventing allergic conjunctivitis in a subject in need thereof, comprising administering an effective amount of an artificial polypeptide of formula (III): XY(III) administering to a subject: 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 portion containing 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.

[0020] In some embodiments, Y comprises a sequence having at least 90% identity to SEQ ID NO:2, Y comprises a sequence having at least 95% identity to 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 to SEQ ID NO:2. In some embodiments, Y comprises a sequence having at least 95% identity to 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 of 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 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 hydrophilic amino acids in X is 15 or less, and / or the total number of hydrophobic amino acids in X is 10 or less. 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 15 or less. In some embodiments, the total number of hydrophobic amino acids in X is 10 or less. In some embodiments, X comprises a sequence having at least 90% identity to any one selected from SEQ ID NOs: 23-27, or X comprises a sequence having at least 95% identity to any one selected from SEQ ID NOs: 23-27. In some embodiments, X comprises a sequence having at least 90% identity to any one selected from SEQ ID NOs: 23-27. In some embodiments, X comprises a sequence having at least 95% identity to any one selected from SEQ ID NOs: 23-27.

[0022] In some embodiments, the polypeptide comprises a sequence having at least 90% identity to SEQ ID NOs: 49-53.

[0023] In some embodiments, 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 phlyctenular keratoconjunctivitis. In some embodiments, the seasonal allergic conjunctivitis is caused or partially caused by a seasonal allergen. In some embodiments, the seasonal allergen is at least one selected from the group consisting of tree pollen, weed pollen, grass pollen, and mold spores. In some embodiments, the perennial allergic conjunctivitis is caused or partially caused by a perennial allergen. In some embodiments, the perennial allergen is at least one selected from the group consisting of house dust mites, cockroaches, and animal dander. In some embodiments, the vernal keratoconjunctivitis is at least one selected from the group consisting of palpebral vernal keratoconjunctivitis, limbal vernal keratoconjunctivitis, and mixed vernal keratoconjunctivitis. In some embodiments, giant papillary conjunctivitis is caused or partially caused by repeated mechanical irritation of the conjunctiva. In some embodiments, 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 prostheses, use of conjunctival sutures, use of protruding scleral buckles, and raised corneal scars. In some embodiments, atopic keratoconjunctivitis is accompanied by atopic dermatitis and / or asthma. In some embodiments, phlyctenular keratoconjunctivitis is caused or partially caused 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 the group consisting of bacteria (e.g., Staphylococcus aureus, Streptococcus viridians, Mycobacterium tuberculosis), viruses (e.g., herpes simplex virus), chlamydia, fungi (e.g., Candida, e.g., Candida albicans), and parasites (e.g., tapeworms, e.g., Hymenolepis nana; and nematodes).In some embodiments, the subject does not have any ocular disease selected from the group consisting of viral conjunctivitis, bacterial conjunctivitis, chemical conjunctivitis, and dry eye or a dry eye-related disorder. In some embodiments, the subject experiences at least one symptom selected from the group consisting of conjunctival redness, conjunctival edema, conjunctival congestion, eyelid redness, eyelid edema, eyelid congestion, itchy eyes, visible corneal damage, mucous eye discharge, watery eye discharge, tearing, photophobia, foreign body sensation, and difficulty opening the eyes prior to administration of the artificial polypeptide of Formula (III). In some embodiments, the subject, after administration of at least one dose of the artificial polypeptide of Formula (III), exhibits a reduction in at least one symptom selected from the group consisting of conjunctival redness, conjunctival edema, conjunctival congestion, eyelid redness, eyelid edema, eyelid congestion, itchy eyes, visible corneal damage, mucous discharge, watery discharge, tearing, photophobia, foreign body sensation, and difficulty opening the eye. In some embodiments, the subject, after administration of at least one dose of the artificial polypeptide of Formula (III), exhibits an improvement in at least one tissue selected from the group consisting of the conjunctiva, cornea, anterior chamber, iris, pupil, vitreous, and fundus.

[0024] In another aspect, a method is provided for treating or preventing allergic conjunctivitis in a subject in need thereof, comprising administering an effective amount of an artificial polypeptide of formula (IV): XY(IV) administering to a subject: 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 portion containing a sequence having at least 80% identity with SEQ ID NO: 2, X comprises a sequence having at most 90% identity to SEQ ID NO:1.

[0025] In some embodiments, X comprises a sequence having at most 80% identity to SEQ ID NO:1, X comprises a sequence having at most 70% identity to SEQ ID NO:1, or X comprises a sequence having at most 50% identity to SEQ ID NO:1. In some embodiments, X comprises a sequence having at most 80% identity to SEQ ID NO:1. In some embodiments, X comprises a sequence having at most 70% identity to SEQ ID NO:1. In some embodiments, X comprises a sequence having at most 50% identity to 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 hydrophilic amino acids in X is 15 or less, and / or the total number of hydrophobic amino acids in X is 10 or less. 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 15 or less. In some embodiments, the total number of hydrophobic amino acids in X is 10 or less. In some embodiments, X comprises a sequence having at least 90% identity to any one selected from SEQ ID NOs: 19-22 and 76-79, or X comprises a sequence having at least 95% identity to any one selected from SEQ ID NOs: 19-22 and 76-79. In some embodiments, X comprises a sequence having at least 90% identity to any one selected from SEQ ID NOs: 19-22 and 76-79. In some embodiments, X comprises a sequence having at least 95% identity to any one selected from SEQ ID NOs: 19-22 and 76-79.

[0026] In some embodiments, Y comprises a sequence having at least 90% identity to SEQ ID NO:2, Y comprises a sequence having at least 95% identity to 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 to SEQ ID NO:2. In some embodiments, Y comprises a sequence having at least 95% identity to 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 of 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 to any one selected from SEQ ID NOs: 45-48 and 86-89.

[0028] In some embodiments, 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 phlyctenular keratoconjunctivitis. In some embodiments, the seasonal allergic conjunctivitis is caused or partially caused by a seasonal allergen. In some embodiments, the seasonal allergen is at least one selected from the group consisting of tree pollen, weed pollen, grass pollen, and mold spores. In some embodiments, the perennial allergic conjunctivitis is caused or partially caused by a perennial allergen. In some embodiments, the perennial allergen is at least one selected from the group consisting of house dust mites, cockroaches, and animal dander. In some embodiments, the vernal keratoconjunctivitis is at least one selected from the group consisting of palpebral vernal keratoconjunctivitis, limbal vernal keratoconjunctivitis, and mixed vernal keratoconjunctivitis. In some embodiments, giant papillary conjunctivitis is caused or partially caused by repeated mechanical irritation of the conjunctiva. In some embodiments, 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 prostheses, use of conjunctival sutures, use of protruding scleral buckles, and raised corneal scars. In some embodiments, atopic keratoconjunctivitis is accompanied by atopic dermatitis and / or asthma. In some embodiments, phlyctenular keratoconjunctivitis is caused or partially caused 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 the group consisting of bacteria (e.g., Staphylococcus aureus, Streptococcus viridians, Mycobacterium tuberculosis), viruses (e.g., herpes simplex virus), chlamydia, fungi (e.g., Candida, e.g., Candida albicans), and parasites (e.g., tapeworms, e.g., Hymenolepis nana; and nematodes).In some embodiments, the subject does not have any ocular disease selected from the group consisting of viral conjunctivitis, bacterial conjunctivitis, chemical conjunctivitis, and dry eye or a dry eye-related disorder. In some embodiments, the subject experiences at least one symptom selected from the group consisting of conjunctival redness, conjunctival edema, conjunctival congestion, eyelid redness, eyelid edema, eyelid congestion, itchy eyes, visible corneal damage, mucous eye discharge, watery eye discharge, tearing, photophobia, foreign body sensation, and difficulty opening the eyes prior to administration of the artificial polypeptide of Formula (IV). In some embodiments, the subject, after administration of at least one dose of the artificial polypeptide of Formula (IV), exhibits a reduction in at least one symptom selected from the group consisting of conjunctival redness, conjunctival edema, conjunctival congestion, eyelid redness, eyelid edema, eyelid congestion, itchy eyes, visible corneal damage, mucous eye discharge, watery eye discharge, tearing, photophobia, foreign body sensation, and difficulty opening the eye. In some embodiments, the subject, after administration of at least one dose of the artificial polypeptide of Formula (IV), exhibits an improvement in at least one tissue selected from the group consisting of the conjunctiva, cornea, anterior chamber, iris, pupil, vitreous, and fundus.

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

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

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

[0032] In some embodiments, Y comprises a sequence having at most 80% identity to SEQ ID NO:2, Y comprises a sequence having at most 70% identity to SEQ ID NO:2, or Y comprises a sequence having at most 50% identity to SEQ ID NO:2. In some embodiments, Y comprises a sequence having at most 80% identity to SEQ ID NO:2. In some embodiments, Y comprises a sequence having at most 70% identity to SEQ ID NO:2. In some embodiments, Y comprises a sequence having at most 50% identity to SEQ ID NO:2. In some embodiments, Y comprises a sequence having at least 80% identity to any one selected from SEQ ID NOs:97-103, Y comprises a sequence having at least 90% identity to any one selected from SEQ ID NOs:97-103, Y comprises a sequence having at least 95% identity to any one selected from SEQ ID NOs:97-103, or Y comprises a sequence that is any one selected from SEQ ID NOs:97-103. In some embodiments, Y comprises a sequence having at least 80% identity to any one selected from SEQ ID NOs: 97-103. In some embodiments, Y comprises a sequence having at least 90% identity to any one selected from SEQ ID NOs: 97-103. In some embodiments, Y comprises a sequence having at least 95% identity to any one selected from SEQ ID NOs: 97-103. In some embodiments, Y comprises a sequence that is any one selected from SEQ ID NOs: 97-103.

[0033] In some embodiments, the polypeptide comprises a sequence having at least 90% identity to any of SEQ ID NOs: 53-56 and 104-110.

[0034] In some embodiments, 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 phlyctenular keratoconjunctivitis. In some embodiments, the seasonal allergic conjunctivitis is caused or partially caused by a seasonal allergen. In some embodiments, the seasonal allergen is at least one selected from the group consisting of tree pollen, weed pollen, grass pollen, and mold spores. In some embodiments, the perennial allergic conjunctivitis is caused or partially caused by a perennial allergen. In some embodiments, the perennial allergen is at least one selected from the group consisting of house dust mites, cockroaches, and animal dander. In some embodiments, the vernal keratoconjunctivitis is at least one selected from the group consisting of palpebral vernal keratoconjunctivitis, limbal vernal keratoconjunctivitis, and mixed vernal keratoconjunctivitis. In some embodiments, giant papillary conjunctivitis is caused or partially caused by repeated mechanical irritation of the conjunctiva. In some embodiments, 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 prostheses, use of conjunctival sutures, use of protruding scleral buckles, and raised corneal scars. In some embodiments, atopic keratoconjunctivitis is accompanied by atopic dermatitis and / or asthma. In some embodiments, phlyctenular keratoconjunctivitis is caused or partially caused 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 the group consisting of bacteria (e.g., Staphylococcus aureus, Streptococcus viridians, Mycobacterium tuberculosis), viruses (e.g., herpes simplex virus), chlamydia, fungi (e.g., Candida, e.g., Candida albicans), and parasites (e.g., tapeworms, e.g., Hymenolepis nana; and nematodes).In some embodiments, the subject does not have any ocular disease selected from the group consisting of viral conjunctivitis, bacterial conjunctivitis, chemical conjunctivitis, and dry eye or a dry eye-related disorder. In some embodiments, the subject experiences at least one symptom selected from the group consisting of conjunctival redness, conjunctival edema, conjunctival congestion, eyelid redness, eyelid edema, eyelid congestion, itchy eyes, visible corneal damage, mucous eye discharge, watery eye discharge, tearing, photophobia, foreign body sensation, and difficulty opening the eyes prior to administration of the artificial polypeptide of Formula (V). In some embodiments, the subject, after administration of at least one dose of the artificial polypeptide of Formula (V), exhibits a reduction in at least one symptom selected from the group consisting of conjunctival redness, conjunctival edema, conjunctival congestion, eyelid redness, eyelid edema, eyelid congestion, itchy eyes, visible corneal damage, mucous discharge, watery discharge, tearing, photophobia, foreign body sensation, and difficulty opening the eye. In some embodiments, the subject, after administration of at least one dose of the artificial polypeptide of Formula (V), exhibits an improvement in at least one tissue selected from the group consisting of the conjunctiva, cornea, anterior chamber, iris, pupil, vitreous, and fundus.

[0035] In another aspect, a method is provided for treating or preventing allergic conjunctivitis in a subject in need thereof, comprising administering an effective amount of an artificial polypeptide of formula (VI): XY(VI) administering to a subject: X is a moiety comprising a variant of SEQ ID NO: 1, wherein the variant is characterized in that at least 1, 2, 3, 4, 5, 6, 7, 8, or 9 Ds in SEQ ID NO: 1 are mutated to S, and / or at least 1, 2, 3, 4, 5, or 6 Es in SEQ ID NO: 1 are mutated to T; Y is a moiety comprising a variant of SEQ ID NO:2, wherein the variant is characterized by at least 1, 2, 3, 4, or 5 C's in SEQ ID NO:2 being mutated to A's.

[0036] In some embodiments, X comprises a sequence having at least 70% identity to SEQ ID NO: 1 and / or X comprises a sequence having at most 95% identity to SEQ ID NO: 1. In some embodiments, X comprises a sequence having at least 70% identity to SEQ ID NO: 1. In some embodiments, X comprises a sequence having at most 95% identity to 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 equal to or less 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 equal to or less than 20. In some embodiments, X comprises a sequence having at least 80% identity to any one selected from SEQ ID NOs: 80-83, X comprises a sequence that is any one selected from SEQ ID NOs: 80-83, or X is a sequence that is any one selected from SEQ ID NOs: 80-83. In some embodiments, X comprises a sequence that is at least 80% identity to any one selected from SEQ ID NOs: 80-83. In some embodiments, X comprises a sequence that is any one selected from SEQ ID NOs: 80-83. In some embodiments, X is a sequence that is any one selected from SEQ ID NOs: 80-83.

[0037] In some embodiments, Y comprises a sequence having at least 80% identity to SEQ ID NO:2 and / or Y comprises a sequence having at most 95% identity to SEQ ID NO:2. In some embodiments, Y comprises a sequence having at least 80% identity to SEQ ID NO:2. In some embodiments, Y comprises a sequence having at most 95% identity to SEQ ID NO:2. In some embodiments, at least 50% of the amino acids of 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 is 20 or less. 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 is 20 or less. In some embodiments, Y comprises a sequence having at least 80% identity to 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 to 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 to any one selected from SEQ ID NOs: 90-93, the artificial polypeptide comprises a sequence that is any one selected from SEQ ID NOs: 90-93, or the artificial polypeptide is a sequence that is any one selected from SEQ ID NOs: 90-93. In some embodiments, the artificial polypeptide comprises a sequence that is at least 80% identity to any one selected from SEQ ID NOs: 90-93. In some embodiments, the artificial polypeptide comprises a sequence that is any one selected from SEQ ID NOs: 90-93. In some embodiments, the artificial polypeptide is a sequence that is any one selected from SEQ ID NOs: 90-93.

[0039] In some embodiments, 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 phlyctenular keratoconjunctivitis. In some embodiments, the seasonal allergic conjunctivitis is caused or partially caused by a seasonal allergen. In some embodiments, the seasonal allergen is at least one selected from the group consisting of tree pollen, weed pollen, grass pollen, and mold spores. In some embodiments, the perennial allergic conjunctivitis is caused or partially caused by a perennial allergen. In some embodiments, the perennial allergen is at least one selected from the group consisting of house dust mites, cockroaches, and animal dander. In some embodiments, the vernal keratoconjunctivitis is at least one selected from the group consisting of palpebral vernal keratoconjunctivitis, limbal vernal keratoconjunctivitis, and mixed vernal keratoconjunctivitis. In some embodiments, giant papillary conjunctivitis is caused or partially caused by repeated mechanical irritation of the conjunctiva. In some embodiments, 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 prostheses, use of conjunctival sutures, use of protruding scleral buckles, and raised corneal scars. In some embodiments, atopic keratoconjunctivitis is accompanied by atopic dermatitis and / or asthma. In some embodiments, phlyctenular keratoconjunctivitis is caused or partially caused 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 the group consisting of bacteria (e.g., Staphylococcus aureus, Streptococcus viridians, Mycobacterium tuberculosis), viruses (e.g., herpes simplex virus), chlamydia, fungi (e.g., Candida, e.g., Candida albicans), and parasites (e.g., tapeworms, e.g., Hymenolepis nana; and nematodes).In some embodiments, the subject does not have any ocular disease selected from the group consisting of viral conjunctivitis, bacterial conjunctivitis, chemical conjunctivitis, and dry eye or a dry eye-related disorder. In some embodiments, the subject experiences at least one symptom selected from the group consisting of conjunctival redness, conjunctival edema, conjunctival congestion, eyelid redness, eyelid edema, eyelid congestion, itchy eyes, visible corneal damage, mucous eye discharge, watery eye discharge, tearing, photophobia, foreign body sensation, and difficulty opening the eyes prior to administration of the artificial polypeptide of Formula (VI). In some embodiments, the subject, after administration of at least one dose of an artificial polypeptide of Formula (VI), exhibits a reduction in at least one symptom selected from the group consisting of conjunctival redness, conjunctival edema, conjunctival congestion, eyelid redness, eyelid edema, eyelid congestion, itchy eyes, visible corneal damage, mucous discharge, watery discharge, tearing, photophobia, foreign body sensation, and difficulty opening the eye. In some embodiments, the subject, after administration of at least one dose of an artificial polypeptide of Formula (VI), exhibits an improvement in at least one tissue selected from the group consisting of the conjunctiva, cornea, anterior chamber, iris, pupil, vitreous, and fundus.

[0040] In another aspect, a method is provided for treating or preventing allergic conjunctivitis in a subject in need thereof, comprising administering an effective amount of an artificial polypeptide of formula (VII): XY(VII) administering to a subject: X is a portion of SEQ ID NO: 1 that comprises a variant, characterized in that the variant has at least 1, 2, 3, 4, or 5 amino acid insertions compared to SEQ ID NO: 1; Y is a moiety containing 10 to 30 amino acids, and Y includes a sequence having at least 15 consecutive AA of SEQ ID NO:2.

[0041] In some embodiments, the amino acid insertion is located N-terminal to X, and / or the inserted amino acid is M. In some embodiments, the amino acid insertion is located N-terminal to 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 at most 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, at most 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 is 20 or less. 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 20 or less. In some embodiments, X comprises a sequence having at least 80% identity to 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 to 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 moiety comprising a variant of SEQ ID NO:2, characterized in that the variant 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 acids truncated relative to SEQ ID NO:2, optionally wherein 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 acids truncated relative to SEQ ID NO:2. In some embodiments, Y, is a moiety comprising a variant of SEQ ID NO:2, characterized in that the variant 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 acids truncated relative to SEQ ID NO:2. In some embodiments, 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 comprises 15-25 amino acids, Y comprises 18-25 amino acids, or Y comprises 20-25 amino acids. In some embodiments, Y comprises 15-25 amino acids. In some embodiments, Y comprises 18-25 amino acids. In some embodiments, Y comprises 20-25 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 is 10 or less and / or the total number of W, Y, F, M, L, I, and V in Y is 15 or less. In some embodiments, the total number of R, K, T, A, N, Q, D, E, S, and G in Y is 10 or less. In some embodiments, the total number of W, Y, F, M, L, I, and V in Y is 15 or less. In some embodiments, Y comprises a sequence having at least 80% identity to any one selected from SEQ ID NOs: 97-103, Y comprises a sequence that is any one selected from SEQ ID NOs: 97-103, or Y is a sequence that is any one selected from SEQ ID NOs: 97-103. In some embodiments, Y comprises a sequence that is at least 80% identity to any one selected from SEQ ID NOs: 97-103.In some embodiments, Y comprises a sequence that is any one selected from SEQ ID NOs: 97 to 103. In some embodiments, Y is a sequence that is any one selected from SEQ ID NOs: 97 to 103.

[0044] In some embodiments, the artificial polypeptide comprises a sequence having at least 80% identity to any one selected from SEQ ID NOs: 104-110, the artificial polypeptide comprises a sequence that is any one selected from SEQ ID NOs: 104-110, or the artificial polypeptide is a sequence that is any one selected from SEQ ID NOs: 104-110. In some embodiments, the artificial polypeptide comprises a sequence that is at least 80% identity to any one selected from SEQ ID NOs: 104-110. In some embodiments, the artificial polypeptide comprises a sequence that is any one selected from SEQ ID NOs: 104-110. In some embodiments, the artificial polypeptide is a sequence that is any one selected from SEQ ID NOs: 104-110.

[0045] In some embodiments, 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 phlyctenular keratoconjunctivitis. In some embodiments, the seasonal allergic conjunctivitis is caused or partially caused by a seasonal allergen. In some embodiments, the seasonal allergen is at least one selected from the group consisting of tree pollen, weed pollen, grass pollen, and mold spores. In some embodiments, the perennial allergic conjunctivitis is caused or partially caused by a perennial allergen. In some embodiments, the perennial allergen is at least one selected from the group consisting of house dust mites, cockroaches, and animal dander. In some embodiments, the vernal keratoconjunctivitis is at least one selected from the group consisting of palpebral vernal keratoconjunctivitis, limbal vernal keratoconjunctivitis, and mixed vernal keratoconjunctivitis. In some embodiments, giant papillary conjunctivitis is caused or partially caused by repeated mechanical irritation of the conjunctiva. In some embodiments, 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 prostheses, use of conjunctival sutures, use of protruding scleral buckles, and raised corneal scars. In some embodiments, atopic keratoconjunctivitis is accompanied by atopic dermatitis and / or asthma. In some embodiments, phlyctenular keratoconjunctivitis is caused or partially caused 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 the group consisting of bacteria (e.g., Staphylococcus aureus, Streptococcus viridians, Mycobacterium tuberculosis), viruses (e.g., herpes simplex virus), chlamydia, fungi (e.g., Candida, e.g., Candida albicans), and parasites (e.g., tapeworms, e.g., Hymenolepis nana; and nematodes).In some embodiments, the subject does not have any ocular disease selected from the group consisting of viral conjunctivitis, bacterial conjunctivitis, chemical conjunctivitis, and dry eye or a dry eye-related disorder. In some embodiments, the subject experiences at least one symptom selected from the group consisting of conjunctival redness, conjunctival edema, conjunctival congestion, eyelid redness, eyelid edema, eyelid congestion, itchy eyes, visible corneal damage, mucous eye discharge, watery eye discharge, tearing, photophobia, foreign body sensation, and difficulty opening the eyes prior to administration of the artificial polypeptide of Formula (VII). In some embodiments, the subject, after administration of at least one dose of an artificial polypeptide of Formula (VII), exhibits a reduction in at least one symptom selected from the group consisting of conjunctival redness, conjunctival edema, conjunctival congestion, eyelid redness, eyelid edema, eyelid congestion, itchy eyes, visible corneal damage, mucous discharge, watery discharge, tearing, photophobia, foreign body sensation, and difficulty opening the eye. In some embodiments, the subject, after administration of at least one dose of an artificial polypeptide of Formula (VII), exhibits an improvement in at least one tissue selected from the group consisting of the conjunctiva, cornea, anterior chamber, iris, pupil, vitreous, and fundus.

[0046] In another aspect, a method for treating or preventing allergic conjunctivitis in a subject in need thereof is provided, comprising administering an effective amount of an artificial polypeptide variant of Formula (I). XY(I) administering to a subject: X is a portion containing a sequence having at least 80% identity with 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 contains a total number of cysteines (C) of less than 5, The mutant is characterized in that at least 1, 2, 3, 4, 5, 6, 7, 8, or 9 Ds in X are mutated to S, and / or at least 1, 2, 3, 4, 5, or 6 Es in X are mutated to T.

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

[0048] In some embodiments, Y, comprises a total number of cysteines (C) less than 4, or Y, comprises a total number of cysteines (C) less than 3. In some embodiments, Y, comprises a total number of cysteines (C) less than 4. In some embodiments, Y, comprises a total number of cysteines (C) less than 3. 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 5 or less. 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, is 5 or less. In some embodiments, Y comprises a sequence having at least 90% identity to any one selected from SEQ ID NOs: 3-15, 58-61 and 84-85, or Y comprises a sequence having at least 90% identity to any one selected from SEQ ID NOs: 3-18, 58-61 and 84-85. In some embodiments, Y comprises a sequence having at least 90% identity to any one selected from SEQ ID NOs: 3-15, 58-61 and 84-85. In some embodiments, Y comprises a sequence having at least 90% identity to any one selected from SEQ ID NOs: 3-18, 58-61 and 84-85.

[0049] In some embodiments, 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 phlyctenular keratoconjunctivitis. In some embodiments, the seasonal allergic conjunctivitis is caused or partially caused by a seasonal allergen. In some embodiments, the seasonal allergen is at least one selected from the group consisting of tree pollen, weed pollen, grass pollen, and mold spores. In some embodiments, the perennial allergic conjunctivitis is caused or partially caused by a perennial allergen. In some embodiments, the perennial allergen is at least one selected from the group consisting of house dust mites, cockroaches, and animal dander. In some embodiments, the vernal keratoconjunctivitis is at least one selected from the group consisting of palpebral vernal keratoconjunctivitis, limbal vernal keratoconjunctivitis, and mixed vernal keratoconjunctivitis. In some embodiments, giant papillary conjunctivitis is caused or partially caused by repeated mechanical irritation of the conjunctiva. In some embodiments, 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 prostheses, use of conjunctival sutures, use of protruding scleral buckles, and raised corneal scars. In some embodiments, atopic keratoconjunctivitis is accompanied by atopic dermatitis and / or asthma. In some embodiments, phlyctenular keratoconjunctivitis is caused or partially caused 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 the group consisting of bacteria (e.g., Staphylococcus aureus, Streptococcus viridians, Mycobacterium tuberculosis), viruses (e.g., herpes simplex virus), chlamydia, fungi (e.g., Candida, e.g., Candida albicans), and parasites (e.g., tapeworms, e.g., Hymenolepis nana; and nematodes).In some embodiments, the subject does not have any ocular disease selected from the group consisting of viral conjunctivitis, bacterial conjunctivitis, chemical conjunctivitis, and dry eye or a dry eye-related disorder. In some embodiments, the subject, prior to administration of the artificial polypeptide variant of Formula (I), experiences at least one symptom selected from the group consisting of conjunctival redness, conjunctival edema, conjunctival congestion, eyelid redness, eyelid edema, eyelid congestion, itchy eyes, visible corneal damage, mucous eye discharge, watery eye discharge, tearing, photophobia, foreign body sensation, and difficulty opening the eyes. In some embodiments, the subject, after administration of at least one dose of the artificial polypeptide variant of Formula (I), exhibits a reduction in at least one symptom selected from the group consisting of conjunctival redness, conjunctival edema, conjunctival congestion, eyelid redness, eyelid edema, eyelid congestion, itchy eyes, visible corneal damage, mucous eye discharge, watery eye discharge, tearing, photophobia, foreign body sensation, and difficulty opening the eye. In some embodiments, the subject, after administration of at least one dose of the artificial polypeptide variant of Formula (I), exhibits an improvement in at least one tissue selected from the group consisting of the conjunctiva, cornea, anterior chamber, iris, pupil, vitreous, and fundus.

[0050] In another aspect, a method is provided for treating or preventing allergic conjunctivitis in a subject in need thereof, comprising administering an effective amount of an artificial polypeptide variant of formula (II) XY(II) administering to a subject: X is a portion containing a sequence having at least 80% identity with 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 having at most 90% identity to SEQ ID NO:2, The variant is characterized in that at least 1, 2, 3, 4, 5, 6, 7, 8, or 9 Ds in X are mutated to S, and / or at least 1, 2, 3, 4, 5, or 6 Es in X are mutated to T.

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

[0052] In some embodiments, Y comprises a sequence having at most 80% identity to SEQ ID NO:2, or Y comprises a sequence having at most 70% identity to SEQ ID NO:2. In some embodiments, Y comprises a sequence having at most 80% identity to SEQ ID NO:2. In some embodiments, Y comprises a sequence having at most 70% identity to 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 5 or less. 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 is 5 or less. In some embodiments, Y comprises a sequence having at least 90% identity to any one selected from SEQ ID NOs: 16-18, or Y comprises a sequence having at least 95% identity to any one selected from SEQ ID NOs: 16-18. In some embodiments, Y comprises a sequence having at least 90% identity to any one selected from SEQ ID NOs: 16-18. In some embodiments, Y comprises a sequence having at least 95% identity to any one selected from SEQ ID NOs: 16-18.

[0053] In some embodiments, 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 phlyctenular keratoconjunctivitis. In some embodiments, the seasonal allergic conjunctivitis is caused or partially caused by a seasonal allergen. In some embodiments, the seasonal allergen is at least one selected from the group consisting of tree pollen, weed pollen, grass pollen, and mold spores. In some embodiments, the perennial allergic conjunctivitis is caused or partially caused by a perennial allergen. In some embodiments, the perennial allergen is at least one selected from the group consisting of house dust mites, cockroaches, and animal dander. In some embodiments, the vernal keratoconjunctivitis is at least one selected from the group consisting of palpebral vernal keratoconjunctivitis, limbal vernal keratoconjunctivitis, and mixed vernal keratoconjunctivitis. In some embodiments, giant papillary conjunctivitis is caused or partially caused by repeated mechanical irritation of the conjunctiva. In some embodiments, 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 prostheses, use of conjunctival sutures, use of protruding scleral buckles, and raised corneal scars. In some embodiments, atopic keratoconjunctivitis is accompanied by atopic dermatitis and / or asthma. In some embodiments, phlyctenular keratoconjunctivitis is caused or partially caused 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 the group consisting of bacteria (e.g., Staphylococcus aureus, Streptococcus viridians, Mycobacterium tuberculosis), viruses (e.g., herpes simplex virus), chlamydia, fungi (e.g., Candida, e.g., Candida albicans), and parasites (e.g., tapeworms, e.g., Hymenolepis nana; and nematodes).In some embodiments, the subject does not have any ocular disease selected from the group consisting of viral conjunctivitis, bacterial conjunctivitis, chemical conjunctivitis, and dry eye or a dry eye-related disorder. In some embodiments, the subject, prior to administration of the artificial polypeptide variant of Formula (II), experiences at least one symptom selected from the group consisting of conjunctival redness, conjunctival edema, conjunctival congestion, eyelid redness, eyelid edema, eyelid congestion, itchy eyes, visible corneal damage, mucous eye discharge, watery eye discharge, tearing, photophobia, foreign body sensation, and difficulty opening the eyes. In some embodiments, the subject, after administration of at least one dose of the artificial polypeptide variant of Formula (II), exhibits a reduction in at least one symptom selected from the group consisting of conjunctival redness, conjunctival edema, conjunctival congestion, eyelid redness, eyelid edema, eyelid congestion, itchy eyes, visible corneal damage, mucous eye discharge, watery eye discharge, tearing, photophobia, foreign body sensation, and difficulty opening the eye. In some embodiments, the subject, after administration of at least one dose of the artificial polypeptide variant of Formula (II), exhibits an improvement in at least one tissue selected from the group consisting of the conjunctiva, cornea, anterior chamber, iris, pupil, vitreous, and fundus.

[0054] In another aspect, a method is provided for treating or preventing allergic conjunctivitis in a subject in need thereof, comprising administering an effective amount of an artificial polypeptide variant of formula (III) XY(III) administering to a subject: 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 portion containing 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; The mutant is characterized in that at least 1, 2, 3, 4, 5, 6, 7, 8, or 9 Ds in X are mutated to S, and / or at least 1, 2, 3, 4, 5, or 6 Es in X are mutated to T.

[0055] In some embodiments, at least 20% of the amino acids of X are selected from R, K, N, D, Q, E, and H; at least 30% of the amino acids of X are selected from R, K, N, D, Q, E, and H; at most 90% of the amino acids of X are selected from R, K, N, D, Q, E, and H; and / or at most 80% of the amino acids of X are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 20% of the amino acids of X are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 30% of the amino acids of X are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 90% of the amino acids of X are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 80% of the amino acids of X are selected from R, K, N, D, Q, E, and H. In some embodiments, X comprises a sequence having at least 70% identity to 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 15 or less, and / or the total number of hydrophilic amino acids in X is 10 or less. 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 hydrophilic amino acids in X is 15 or less.In some embodiments, the total number of hydrophobic amino acids in X is 10 or less.

[0056] In some embodiments, Y comprises a sequence having at least 90% identity to 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 to 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 of Y are selected from I, V, L, F, C, M, and A.

[0057] In some embodiments, 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 phlyctenular keratoconjunctivitis. In some embodiments, the seasonal allergic conjunctivitis is caused or partially caused by a seasonal allergen. In some embodiments, the seasonal allergen is at least one selected from the group consisting of tree pollen, weed pollen, grass pollen, and mold spores. In some embodiments, the perennial allergic conjunctivitis is caused or partially caused by a perennial allergen. In some embodiments, the perennial allergen is at least one selected from the group consisting of house dust mites, cockroaches, and animal dander. In some embodiments, the vernal keratoconjunctivitis is at least one selected from the group consisting of palpebral vernal keratoconjunctivitis, limbal vernal keratoconjunctivitis, and mixed vernal keratoconjunctivitis. In some embodiments, giant papillary conjunctivitis is caused or partially caused by repeated mechanical irritation of the conjunctiva. In some embodiments, 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 prostheses, use of conjunctival sutures, use of protruding scleral buckles, and raised corneal scars. In some embodiments, atopic keratoconjunctivitis is accompanied by atopic dermatitis and / or asthma. In some embodiments, phlyctenular keratoconjunctivitis is caused or partially caused 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 the group consisting of bacteria (e.g., Staphylococcus aureus, Streptococcus viridians, Mycobacterium tuberculosis), viruses (e.g., herpes simplex virus), chlamydia, fungi (e.g., Candida, e.g., Candida albicans), and parasites (e.g., tapeworms, e.g., Hymenolepis nana; and nematodes).In some embodiments, the subject does not have any ocular disease selected from the group consisting of viral conjunctivitis, bacterial conjunctivitis, chemical conjunctivitis, and dry eye or a dry eye-related disorder. In some embodiments, the subject, prior to administration of the artificial polypeptide variant of Formula (III), experiences at least one symptom selected from the group consisting of conjunctival redness, conjunctival edema, conjunctival congestion, eyelid redness, eyelid edema, eyelid congestion, itchy eyes, visible corneal damage, mucous eye discharge, watery eye discharge, tearing, photophobia, foreign body sensation, and difficulty opening the eyes. In some embodiments, the subject, after administration of at least one dose of the artificial polypeptide variant of Formula (III), exhibits a reduction in at least one symptom selected from the group consisting of conjunctival redness, conjunctival edema, conjunctival congestion, eyelid redness, eyelid edema, eyelid congestion, itchy eyes, visible corneal damage, mucous eye discharge, watery eye discharge, tearing, photophobia, foreign body sensation, and difficulty opening the eye. In some embodiments, the subject, after administration of at least one dose of the artificial polypeptide variant of Formula (III), exhibits an improvement in at least one tissue selected from the group consisting of the conjunctiva, cornea, anterior chamber, iris, pupil, vitreous, and fundus.

[0058] In another aspect, a method is provided for treating or preventing allergic conjunctivitis in a subject in need thereof, comprising administering an effective amount of an artificial polypeptide variant of formula (IV). XY(IV) administering to a subject, 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 portion containing a sequence having at least 80% identity with SEQ ID NO: 2, X comprises a sequence having at most 90% identity to SEQ ID NO: 1; The mutant is characterized in that at least 1, 2, 3, 4, 5, 6, 7, 8, or 9 Ds in X are mutated to S, and / or at least 1, 2, 3, 4, 5, or 6 Es in X are mutated to T.

[0059] In some embodiments, at least 20% of the amino acids of X are selected from R, K, N, D, Q, E, and H; at least 30% of the amino acids of X are selected from R, K, N, D, Q, E, and H; at most 90% of the amino acids of X are selected from R, K, N, D, Q, E, and H; and / or at most 80% of the amino acids of X are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 20% of the amino acids of X are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 30% of the amino acids of X are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 90% of the amino acids of X are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 80% of the amino acids of X are selected from R, K, N, D, Q, E, and H. In some embodiments, X comprises a sequence having at least 70% identity to 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 15 or less, and / or the total number of hydrophilic amino acids in X is 10 or less. 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 hydrophilic amino acids in X is 15 or less. In some embodiments, the total number of hydrophilic amino acids in X is 10 or less.

[0060] In some embodiments, Y comprises a sequence having at least 90% identity to 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 to 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 of Y are selected from I, V, L, F, C, M, and A.

[0061] In some embodiments, 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 phlyctenular keratoconjunctivitis. In some embodiments, the seasonal allergic conjunctivitis is caused or partially caused by a seasonal allergen. In some embodiments, the seasonal allergen is at least one selected from the group consisting of tree pollen, weed pollen, grass pollen, and mold spores. In some embodiments, the perennial allergic conjunctivitis is caused or partially caused by a perennial allergen. In some embodiments, the perennial allergen is at least one selected from the group consisting of house dust mites, cockroaches, and animal dander. In some embodiments, the vernal keratoconjunctivitis is at least one selected from the group consisting of palpebral vernal keratoconjunctivitis, limbal vernal keratoconjunctivitis, and mixed vernal keratoconjunctivitis. In some embodiments, giant papillary conjunctivitis is caused or partially caused by repeated mechanical irritation of the conjunctiva. In some embodiments, 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 prostheses, use of conjunctival sutures, use of protruding scleral buckles, and raised corneal scars. In some embodiments, atopic keratoconjunctivitis is accompanied by atopic dermatitis and / or asthma. In some embodiments, phlyctenular keratoconjunctivitis is caused or partially caused 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 the group consisting of bacteria (e.g., Staphylococcus aureus, Streptococcus viridians, Mycobacterium tuberculosis), viruses (e.g., herpes simplex virus), chlamydia, fungi (e.g., Candida, e.g., Candida albicans), and parasites (e.g., tapeworms, e.g., Hymenolepis nana; and nematodes).In some embodiments, the subject does not have any ocular disease selected from the group consisting of viral conjunctivitis, bacterial conjunctivitis, chemical conjunctivitis, and dry eye or a dry eye-related disorder. In some embodiments, the subject, prior to administration of the artificial polypeptide variant of Formula (IV), experiences at least one symptom selected from the group consisting of conjunctival redness, conjunctival edema, conjunctival congestion, eyelid redness, eyelid edema, eyelid congestion, itchy eyes, visible corneal damage, mucous eye discharge, watery eye discharge, tearing, photophobia, foreign body sensation, and difficulty opening the eyes. In some embodiments, the subject, after administration of at least one dose of the artificial polypeptide variant of Formula (IV), exhibits a reduction in at least one symptom selected from the group consisting of conjunctival redness, conjunctival edema, conjunctival congestion, eyelid redness, eyelid edema, eyelid congestion, itchy eyes, visible corneal damage, mucous discharge, watery discharge, tearing, photophobia, foreign body sensation, and difficulty opening the eye. In some embodiments, the subject, after administration of at least one dose of the artificial polypeptide variant of Formula (IV), exhibits an improvement in at least one tissue selected from the group consisting of the conjunctiva, cornea, anterior chamber, iris, pupil, vitreous, and fundus.

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

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

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

[0065] In some embodiments, 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 phlyctenular keratoconjunctivitis. In some embodiments, the seasonal allergic conjunctivitis is caused or partially caused by a seasonal allergen. In some embodiments, the seasonal allergen is at least one selected from the group consisting of tree pollen, weed pollen, grass pollen, and mold spores. In some embodiments, the perennial allergic conjunctivitis is caused or partially caused by a perennial allergen. In some embodiments, the perennial allergen is at least one selected from the group consisting of house dust mites, cockroaches, and animal dander. In some embodiments, the vernal keratoconjunctivitis is at least one selected from the group consisting of palpebral vernal keratoconjunctivitis, limbal vernal keratoconjunctivitis, and mixed vernal keratoconjunctivitis. In some embodiments, giant papillary conjunctivitis is caused or partially caused by repeated mechanical irritation of the conjunctiva. In some embodiments, 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 prostheses, use of conjunctival sutures, use of protruding scleral buckles, and raised corneal scars. In some embodiments, atopic keratoconjunctivitis is accompanied by atopic dermatitis and / or asthma. In some embodiments, phlyctenular keratoconjunctivitis is caused or partially caused 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 the group consisting of bacteria (e.g., Staphylococcus aureus, Streptococcus viridians, Mycobacterium tuberculosis), viruses (e.g., herpes simplex virus), chlamydia, fungi (e.g., Candida, e.g., Candida albicans), and parasites (e.g., tapeworms, e.g., Hymenolepis nana; and nematodes).In some embodiments, the subject does not have any ocular disease selected from the group consisting of viral conjunctivitis, bacterial conjunctivitis, chemical conjunctivitis, and dry eye or a dry eye-related disorder. In some embodiments, the subject experiences at least one symptom selected from the group consisting of conjunctival redness, conjunctival edema, conjunctival congestion, eyelid redness, eyelid edema, eyelid congestion, itchy eyes, visible corneal damage, mucous eye discharge, watery eye discharge, tearing, photophobia, foreign body sensation, and difficulty opening the eyes prior to administration of the artificial polypeptide variant of Formula (V). In some embodiments, the subject, after administration of at least one dose of the artificial polypeptide variant of Formula (V), exhibits a reduction in at least one symptom selected from the group consisting of conjunctival redness, conjunctival edema, conjunctival congestion, eyelid redness, eyelid edema, eyelid congestion, itchy eyes, visible corneal damage, mucous discharge, watery discharge, tearing, photophobia, foreign body sensation, and difficulty opening the eye. In some embodiments, the subject, after administration of at least one dose of the artificial polypeptide variant of Formula (V), exhibits an improvement in at least one tissue selected from the group consisting of the conjunctiva, cornea, anterior chamber, iris, pupil, vitreous, and fundus.

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

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

[0068] In some embodiments, 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 phlyctenular keratoconjunctivitis. In some embodiments, the seasonal allergic conjunctivitis is caused or partially caused by a seasonal allergen. In some embodiments, the seasonal allergen is at least one selected from the group consisting of tree pollen, weed pollen, grass pollen, and mold spores. In some embodiments, the perennial allergic conjunctivitis is caused or partially caused by a perennial allergen. In some embodiments, the perennial allergen is at least one selected from the group consisting of house dust mites, cockroaches, and animal dander. In some embodiments, the vernal keratoconjunctivitis is at least one selected from the group consisting of palpebral vernal keratoconjunctivitis, limbal vernal keratoconjunctivitis, and mixed vernal keratoconjunctivitis. In some embodiments, giant papillary conjunctivitis is caused or partially caused by repeated mechanical irritation of the conjunctiva. In some embodiments, 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 prostheses, use of conjunctival sutures, use of protruding scleral buckles, and raised corneal scars. In some embodiments, atopic keratoconjunctivitis is accompanied by atopic dermatitis and / or asthma. In some embodiments, phlyctenular keratoconjunctivitis is caused or partially caused 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 the group consisting of bacteria (e.g., Staphylococcus aureus, Streptococcus viridians, Mycobacterium tuberculosis), viruses (e.g., herpes simplex virus), chlamydia, fungi (e.g., Candida, e.g., Candida albicans), and parasites (e.g., tapeworms, e.g., Hymenolepis nana; and nematodes).In some embodiments, 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. In some embodiments, the subject experiences at least one symptom selected from the group consisting of conjunctival redness, conjunctival edema, conjunctival congestion, eyelid redness, eyelid edema, eyelid congestion, itchy eyes, visible corneal damage, mucous eye discharge, watery eye discharge, tearing, photophobia, foreign body sensation, and difficulty opening the eyes prior to administration of a polypeptide having at least 70% identity to any one selected from SEQ ID NO: 28, SEQ ID NO: 57, and SEQ ID NO: 62-74, or a fragment or variant thereof. In some embodiments, the subject exhibits a reduction in at least one symptom selected from the group consisting of conjunctival redness, conjunctival edema, conjunctival congestion, eyelid redness, eyelid edema, eyelid congestion, itchy eyes, visible corneal damage, mucous discharge, watery discharge, tearing, photophobia, foreign body sensation, and difficulty opening the eye after administration of at least one dose of a polypeptide having at least 70% identity to any one selected from SEQ ID NO: 28, SEQ ID NO: 57, and 62-74, or a fragment or variant thereof. In some embodiments, the subject exhibits an improvement in at least one tissue selected from the group consisting of the conjunctiva, cornea, anterior chamber, iris, pupil, vitreous, and fundus after administration of at least one dose of a polypeptide having at least 70% identity to any one selected from SEQ ID NO: 28, SEQ ID NO: 57, and 62-74, or a fragment or variant thereof.

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

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

[0071] In some embodiments, 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 phlyctenular keratoconjunctivitis. In some embodiments, the seasonal allergic conjunctivitis is caused or partially caused by a seasonal allergen. In some embodiments, the seasonal allergen is at least one selected from the group consisting of tree pollen, weed pollen, grass pollen, and mold spores. In some embodiments, the perennial allergic conjunctivitis is caused or partially caused by a perennial allergen. In some embodiments, the perennial allergen is at least one selected from the group consisting of house dust mites, cockroaches, and animal dander. In some embodiments, the vernal keratoconjunctivitis is at least one selected from the group consisting of palpebral vernal keratoconjunctivitis, limbal vernal keratoconjunctivitis, and mixed vernal keratoconjunctivitis. In some embodiments, giant papillary conjunctivitis is caused or partially caused by repeated mechanical irritation of the conjunctiva. In some embodiments, 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 prostheses, use of conjunctival sutures, use of protruding scleral buckles, and raised corneal scars. In some embodiments, atopic keratoconjunctivitis is accompanied by atopic dermatitis and / or asthma. In some embodiments, phlyctenular keratoconjunctivitis is caused or partially caused 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 the group consisting of bacteria (e.g., Staphylococcus aureus, Streptococcus viridians, Mycobacterium tuberculosis), viruses (e.g., herpes simplex virus), chlamydia, fungi (e.g., Candida, e.g., Candida albicans), and parasites (e.g., tapeworms, e.g., Hymenolepis nana; and nematodes).In some embodiments, 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. In some embodiments, the subject experiences at least one symptom selected from the group consisting of conjunctival redness, conjunctival edema, conjunctival congestion, eyelid redness, eyelid edema, eyelid congestion, itchy eyes, visible corneal damage, mucous eye discharge, watery eye discharge, tearing, photophobia, foreign body sensation, and difficulty opening the eyes prior to administration of an artificial polypeptide of Formula (I), (II), (III), (IV), (V), (VI), or (VII), or a variant of the artificial polypeptide of Formula (I), (II), (III), (IV), or (V), or a polypeptide having at least 70% identity to any one selected from SEQ ID NO: 28, SEQ ID NO: 57, and SEQ ID NOs: 62-74, or a fragment or variant thereof. In some embodiments, a subject exhibits a reduction in at least one symptom selected from the group consisting of conjunctival redness, conjunctival edema, conjunctival congestion, eyelid redness, eyelid edema, eyelid congestion, itchy eyes, visible corneal damage, mucous eye discharge, watery eye discharge, tearing, photophobia, foreign body sensation, and difficulty opening the eye after administration of at least one dose of an artificial polypeptide of Formula (I), (II), (III), (IV), (V), (VI), or (VII), or a variant of an artificial polypeptide of (I), (II), (III), (IV), or (V), or a polypeptide having at least 70% identity to any one selected from SEQ ID NO: 28, SEQ ID NO: 57, and 62-74, or a fragment or variant thereof. In some embodiments, a subject exhibits improvement in at least one tissue selected from the group consisting of the conjunctiva, cornea, anterior chamber, iris, pupil, vitreous, 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 variant of an artificial polypeptide of (I), (II), (III), (IV), or (V), or a polypeptide having at least 70% identity to any one selected from SEQ ID NO: 28, SEQ ID NOs: 57, and 62-74, or a fragment or variant thereof.

[0072]

[0013] Further aspects and advantages of the present disclosure will become readily apparent to those skilled in the art from the following detailed description, wherein only illustrative embodiments of the present disclosure are shown and described. As will be realized, the present disclosure is capable of other and different embodiments, and its several details are capable of modifications in various obvious respects, all without departing from the present disclosure. Accordingly, the description is to be regarded as illustrative in nature and not as limiting.

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

[0074] The various features of the present disclosure are set forth with particularity in the appended claims. A better understanding of the features and advantages of the present disclosure will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the invention are utilized, and the accompanying drawings. [Brief explanation of the drawings]

[0075] [Figure 1] FIG. 1 shows the inflammation scores of mice from each group on day 14, measured according to Example 2.

[0076] [Figure 2] FIG. 2 shows the number of scrapes for mice from each group on day 14, measured according to Example 2. DETAILED DESCRIPTION OF THE INVENTION

[0077] Detailed Description definition As used herein, the following terms have the meanings ascribed to them unless specified otherwise.

[0078] As used in this specification and claims, the singular forms "a," "an," and "the" include plural references unless the context clearly dictates otherwise. For example, the term "a cell" includes a plurality of cells, including mixtures thereof.

[0079] As used herein, the terms "comprise," "include," "contain," and variations thereof, are intended to mean open-ended transitional phrases that do not exclude the possibility of additional substances or methods. When such terms are used to describe a particular pharmaceutical composition, formulation, kit, use, or method of the present disclosure, this also encompasses the situation in which the pharmaceutical composition, formulation, kit, use, or method consists of the recited substances or methods. For example, the phrase "the solvent comprises water" also includes the situation in which the solvent consists of water, i.e., the solvent contains exclusively water. In the context of the present disclosure, the term "consisting of" is intended to mean a closed-ended transitional phrase that excludes the possibility of additional substances or methods.

[0080] As used herein, ranges recited in this disclosure are intended to explicitly disclose each endpoint of the range and each integer subsumed within that range, unless otherwise indicated. For example, "X is a moiety comprising 40 to 65 amino acids" means that the number of amino acids in the X moiety 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. As another example, "Y is a moiety containing 10-50 amino acids" means that the number of amino acids in the Y moiety 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. Furthermore, any subranges consisting of these integers are intended to be within the scope of the present disclosure. Thus, "X is a moiety containing 40-65 amino acids" is considered to explicitly disclose subranges, e.g., "X is a moiety containing 41-64 amino acids," "X is a moiety containing 42-63 amino acids," "X is a moiety containing 43-62 amino acids," etc.

[0081] The term "about" or "approximately" is used herein to mean within an acceptable error range for a particular value as determined by one of ordinary skill in the art, which depends in part on how the value is measured or determined, i.e., the limitations of the measurement system. For example, "about" can mean within one standard deviation or within more than one standard deviation, in accordance with practice in the art. Alternatively, "about" can mean within a range of up to 20%, up to 10%, up to 5%, or up to 1% of a given value. When a particular value is described in this application and claims, unless otherwise specified, the term "about" or "approximately" should be assumed to mean within an acceptable error range for that particular value.

[0082] The term "optionally" means that the subsequently described event of a circumstance may or may not occur, and that the description includes cases where the event or circumstance occurs and cases where it does not occur.

[0083] The terms "polypeptide," "peptide," and "protein" are used interchangeably herein to refer to polymers of amino acids of any length. The polymers can be linear or branched, can contain modified amino acids, and can be interrupted by non-amino acids. These terms also encompass amino acid polymers that have been modified, for example, by disulfide bond formation, glycosylation, lipidation, acetylation, phosphorylation, or any other manipulation, such as conjugation with a labeling component.

[0084] As used herein, the term "fragment," when applied to a protein, refers to a truncated form of a native biologically active protein that may or may not retain at least a portion of its therapeutic and / or biological activity.

[0085] The term "variant," as used herein, when applied to a protein, refers to a protein having sequence homology to a native biologically active protein that retains at least a portion of the therapeutic and / or biological activity of the biologically active protein. For example, a variant protein may share at least 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% amino acid sequence identity compared to the reference biologically active protein.

[0086] As used herein, the term "amino acid (AA)" refers to any amino acid, natural and / or unnatural or synthetic, including, but not limited to, glycine and both the D or L optical isomers, as well as amino acid analogs and peptidomimetics. Standard one-letter or three-letter codes are used to designate amino acids.

[0087] The term "naturally occurring L-amino acid" refers to the L optical isomeric forms 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).

[0088] The terms "hydrophilic" and "hydrophobic" refer to the degree of affinity a substance has for water. Hydrophilic substances have a strong affinity for water and tend to be dissolved in, mixed with, or wetted by water, while hydrophobic substances essentially lack affinity for water, tend to repel and not absorb water, and tend not to be dissolved in, mixed with, or wetted by water. Amino acids can be characterized based on 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" refer 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 acids" refers to tryptophan, tyrosine, phenylalanine, methionine, leucine, isoleucine, and valine.

[0089] A "host cell" includes an individual cell or cell culture that can be or has been a recipient of a subject vector. A host cell includes the progeny of a single host cell. The progeny may not necessarily be completely identical (in morphology or in genome total DNA complement content) to the original parent cell.

[0090] "Conjugated," "linked," "fused," and "fusion" are used interchangeably herein and refer to the joining of two additional chemical elements or components together by any means, including chemical conjugation or recombinant means.

[0091] The terms "polynucleotide," "nucleic acid," "nucleotide," and "oligonucleotide" are used interchangeably. They refer to polymeric forms of nucleotides of any length, either deoxyribonucleotides or ribonucleotides, or their analogs. Polynucleotides can have any three-dimensional structure and can perform any function, known or unknown. The following are non-limiting examples of polynucleotides: coding or non-coding regions of a gene or gene fragment, loci / loci defined from 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 can contain modified nucleotides, such as methylated nucleotides and nucleotide analogs. If present, modifications to the nucleotide structure can be introduced before or after assembly of the polymer. The sequence of nucleotides can be interrupted with non-nucleotide components. Polynucleotides can be further modified after polymerization, for example, by conjugation with a labeling component.

[0092] The term "complement of a polynucleotide" refers to a polynucleotide molecule having a complementary base sequence and reverse orientation compared to a reference sequence such that it can hybridize to the reference sequence with complete fidelity.

[0093] The term "recombinant," when applied to a polynucleotide, means that the polynucleotide is the product of various combinations of in vitro cloning, restriction and / or ligation steps and other procedures that result in a construct that can potentially be expressed in a host cell.

[0094] 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 the 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, a homologous polynucleotide is a polynucleotide that hybridizes under stringent conditions as defined herein and has 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 to the sequence.

[0095] The terms "percent identity" and "% identity," when applied to polynucleotide sequences, refer to the percentage of residue matches between at least two polynucleotide sequences aligned using a standardized algorithm. Such algorithms may insert gaps in the sequences being compared to optimize alignment between the two sequences in a standardized and reproducible manner, thereby achieving a more meaningful comparison of the two sequences. Percent identity may be measured over the length of the entire defined polynucleotide sequence, e.g., as defined by a particular SEQ ID NO:, or over a shorter length, e.g., over the length of a fragment obtained from a larger, defined polynucleotide sequence, e.g., 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 contiguous residues. It is understood that such lengths are exemplary only, and any fragment length supported by the sequences set forth in this specification, tables, figures, or sequence listing may be used to describe the length over which percentage identity can be measured.

[0096] "Percent (%) amino acid sequence identity" is defined as the percentage of amino acid residues in a query sequence that are identical to the amino acid residues of a second reference polypeptide sequence or a portion thereof, after aligning the sequences and introducing gaps as necessary to achieve the maximum percent sequence identity, without considering any conservative substitutions as part of the sequence identity, with respect to the polypeptide sequences identified herein. Alignment for the purpose of determining percent amino acid sequence identity can be achieved in a variety of ways within the skill of those skilled 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 the appropriate parameters for measuring alignment, including any algorithms required to achieve maximum alignment across the entire length of the sequences being compared. Percent identity can be measured over the length of the entire defined polypeptide sequence, e.g., as defined by a particular SEQ ID NO:, or over a shorter length, e.g., over the length of a fragment taken from a larger defined polypeptide sequence, e.g., 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 contiguous residues. It will be understood that such lengths are exemplary only, and that any fragment length supported by the sequences shown in the specification, tables, figures, or sequence listing can be used to describe the length over which percentage identity can be measured.

[0097] A "vector" is a nucleic acid molecule, preferably self-replicating in a suitable host, that transfers an inserted nucleic acid molecule into and / or between host cells. The term includes vectors that function primarily for the insertion of DNA or RNA into a cell, replicating vectors that function primarily for the replication of DNA or RNA, and expression vectors that function for the transcription and / or translation of DNA or RNA. Also included are vectors that provide more than one of the above functions. An "expression vector" is a polynucleotide that can be transcribed and translated into polypeptide(s) when introduced into a suitable host cell. An "expression system" usually connotes a suitable host cell comprised of an expression vector that can function to produce a desired expression product.

[0098] The term "physiological conditions" refers to in vitro conditions, including temperature, salt concentration, and pH, that mimic the conditions found in a living host, as well as conditions in a living subject. A host of physiologically relevant conditions for use in in vitro assays have been established. Generally, physiological buffers contain physiological concentrations of salt and are adjusted to a neutral pH in the range of about 6.5 to about 7.8, preferably about 7.0 to about 7.5. Various physiological buffers are listed in Sambrook et al. (1989). Physiologically relevant temperatures range from about 25°C to about 38°C, preferably about 35°C to about 37°C.

[0099] The term "antagonist" as used herein includes any molecule that partially or completely blocks, inhibits, or neutralizes the biological activity of the native polypeptide disclosed herein. A method for identifying a polypeptide antagonist may include contacting the native polypeptide with a candidate antagonist molecule and measuring a detectable change in one or more biological activities normally associated with the native polypeptide. In the context of this disclosure, an antagonist may include a protein, nucleic acid, carbohydrate, antibody, or any other molecule that reduces the effect of a biologically active protein.

[0100] The term "agonist" is used in its broadest sense and includes any molecule that mimics the biological activity of a native polypeptide disclosed herein. Suitable agonist molecules specifically include agonist antibodies or antibody fragments, fragments or amino acid sequence variants of native polypeptides, peptides, small organic molecules, and the like. Methods for identifying agonists of a native polypeptide may include contacting the native polypeptide with a candidate agonist molecule and measuring a detectable change in one or more biological activities normally associated with the native polypeptide.

[0101] For purposes of this specification, the term "activity" refers to the action or effect of a component of a fusion protein that corresponds to that of the corresponding native biologically active protein, and "biological activity" refers to an in vitro or in vivo biological function or effect, including, but not limited to, receptor binding, antagonist activity, agonist activity, or cellular or physiological response.

[0102] As used herein, "treatment" or "treating," "alleviating," and "ameliorating" are used interchangeably. These terms refer to an approach to obtaining beneficial or desired results, including, but not limited to, therapeutic benefit and / or preventative benefit. "Therapeutic benefit" refers to the eradication or amelioration of the underlying disorder being treated. Therapeutic benefit is also achieved by the eradication or amelioration of one or more physiological symptoms associated with the underlying disease state, such that improvement is observed in a subject even though the subject may still be suffering from the underlying disorder. For preventative benefit, the composition can be administered to a subject at risk of developing a particular disease state or a subject reporting one or more physiological symptoms of a disease, even if the disease has not been diagnosed.

[0103] The term "therapeutic effect" refers to a physiological effect caused by a polypeptide of the present disclosure, including, but not limited to, curing, alleviating, ameliorating, or preventing a disease state in a human or other animal, or otherwise enhancing the physical or mental well-being of a human or animal. Determination of a therapeutically effective amount is well within the capabilities of those skilled in the art, especially in light of the detailed disclosure provided herein.

[0104] The term "effective amount" refers to an amount of a biologically active protein, alone or as part of a fusion protein composition, that, when administered to a subject in one dose or in repeated doses, is capable of having any detectable beneficial effect on any symptom, aspect, measured 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 disorder or disease.

[0105] The term "pharmaceutically acceptable" refers to a compound, material, composition, formulation, or dosage form that is suitable for use in contact with the tissues of humans and other animals without excessive toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit / risk ratio, within the scope of sound medical judgment.

[0106] 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 administered directly to a subject in need thereof for prophylactic or therapeutic use.

[0107] The term "pharmaceutically acceptable excipient" refers to a pharmaceutically acceptable material, carrier, or vehicle used for preparing a formulation or dosage form according to the present disclosure. Each excipient must be "acceptable" in the sense of being compatible with the other ingredients of the formulation or dosage form and not injurious to the patient.

[0108] The terms "subject," "individual," or "patient," as used herein, refer to any animal that may be used in this disclosure, including, but not limited to, humans, primates, rodents, dogs, cats, horses, sheep, pigs, etc.

[0109] The terms "administer," "administered," "administers," "administering," and "dosing" are used interchangeably and are defined as providing a compound, composition, formulation, and / or dosage form according to the present disclosure to a subject in need thereof via a route known in the art, including, but not limited to, oral, buccal, topical, transmucosal, transdermal, rectal, and parenteral routes of administration. In some embodiments, an oral route of administration is used. In some embodiments, a parenteral route of administration is used, including intravenous, intraarterial, intramuscular, subcutaneous, intraosseous, and intraperitoneal. In some embodiments, a topical route of administration is used.

[0110] The term "in vivo," as used herein, refers to events that take place in the body of a subject.

[0111] The term "in vitro" as used herein refers to events that occur outside the subject's body. In some embodiments, an in vitro assay encompasses any assay that is performed outside the subject's body. An in vitro assay encompasses cell-based assays in which live or dead cells are used. An in vitro assay also encompasses cell-free assays in which no intact cells are used.

[0112] The term "allergic conjunctivitis" as used herein refers to a class of inflammatory diseases caused by conjunctival hypersensitivity to the stimulation of various allergens.Some common signs and symptoms of allergic conjunctivitis are, among others, redness, swelling or hyperemia of the conjunctiva, redness, swelling or hyperemia of the eyelids, itchy eyes, visible damage to the cornea, mucous discharge, watery discharge, tearing, photophobia, foreign body sensation and difficulty in opening the eyes.It has also been reported that patients may experience some other symptoms, such as nasal itching, sneezing, coughing, short-term blurred vision, distraction, reduced productivity and fatigue.

[0113] The term "seasonal allergic conjunctivitis" refers to the most common form of allergic conjunctivitis associated with seasonal allergies that typically occurs during the spring and summer months, and occasionally during 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.

[0114] The term "perennial allergic conjunctivitis" refers to a mild, chronic form of allergic conjunctivitis that persists throughout the year. Perennial allergic conjunctivitis is thought to be caused or partially caused by perennial allergens, i.e., year-round environmental (usually indoor) allergens, such as house dust mites, cockroaches, and animal dander.

[0115] The term "vernal keratoconjunctivitis" refers to a recurrent, bilateral, self-limiting form of allergic conjunctivitis with cyclical seasonal occurrences. Vernal keratoconjunctivitis is clinically further classified into three subtypes: palpebral vernal keratoconjunctivitis, limbal vernal keratoconjunctivitis, and mixed vernal keratoconjunctivitis. Vernal keratoconjunctivitis is thought to be caused or partially caused by house dust mites, pollen, and / or animal dander. However, for most patients, it is often difficult to identify the allergen.

[0116] The term "giant papillary conjunctivitis" refers to a form of allergic conjunctivitis caused or partially caused by repeated mechanical irritation of the conjunctiva, which may be associated, for example, with contact lens wear, ocular prosthesis use, conjunctival suture use, extruding scleral buckle use, and elevated corneal scars.

[0117] The term "atopic keratoconjunctivitis" refers to a form of chronic (long-lasting) allergic conjunctivitis that affects patients suffering from the skin condition atopic dermatitis. Atopic keratoconjunctivitis is often accompanied by atopic dermatitis and / or asthma.

[0118] The term "phlyctenular keratoconjunctivitis" refers to a form of allergic conjunctivitis caused or partially caused by delayed hypersensitivity or inflammatory reactions of the cornea and conjunctiva to antigens expressed by various pathogens. The triggering antigens are usually bacterial proteins (e.g., 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 (e.g., Candida, e.g., Candida albicans), or parasites (e.g., tapeworms, e.g., Hymenolepis nana; and nematodes). Methods of Treatment and Therapeutic Use

[0119] In one embodiment, a method is provided for treating or preventing allergic conjunctivitis in a subject in need thereof, comprising administering an effective amount of an artificial polypeptide of formula (I): XY(I) administering to a subject: X is a portion containing a sequence having at least 80% identity with 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 contains a total number of cysteines (C) of less than 5.

[0120] In some embodiments, X in Formula (I) can be a hydrophilic moiety, at least 50% of which are selected from R, K, N, D, Q, E, and H. In some embodiments, X in Formula (I) can be a hydrophilic moiety, at least 55% of which are selected from R, K, N, D, Q, E, and H. In some embodiments, X in Formula (I) can be a hydrophilic moiety, at least 60% of which are selected from R, K, N, D, Q, E, and H. In some embodiments, X in Formula (I) can be a hydrophilic moiety, at least 65% of which are selected from R, K, N, D, Q, E, and H. In some embodiments, X in Formula (I) can be a hydrophilic moiety, at least 70% of which are selected from R, K, N, D, Q, E, and H. In some embodiments, X in Formula (I) can be a hydrophilic moiety, at least 75% of which are selected from R, K, N, D, Q, E, and H. In some embodiments, X in formula (I) can be a hydrophilic moiety, at least 80% of which are selected from R, K, N, D, Q, E, and H. In some embodiments, X in formula (I) can be a hydrophilic moiety, at least 85% of which are selected from R, K, N, D, Q, E, and H. In some embodiments, X in formula (I) can be a hydrophilic moiety, at least 90% of which are selected from R, K, N, D, Q, E, and H.

[0121] In some embodiments, X in formula (I) can be a moiety comprising a sequence having at least 80% identity to SEQ ID NO:1. In some embodiments, X is a moiety comprising a sequence having at least 85% identity to SEQ ID NO:1. In some embodiments, X is a moiety comprising a sequence having at least 90% identity to SEQ ID NO:1. In some embodiments, X is a moiety comprising a sequence having at least 95% identity to SEQ ID NO:1. In some embodiments, X is a moiety comprising a sequence having at least 96%, at least 97%, at least 98%, or at least 99% identity to SEQ ID NO:1. In some embodiments, X is a moiety comprising the sequence of SEQ ID NO:1. In some embodiments, X is a moiety that is the sequence of SEQ ID NO:1.

[0122] In some embodiments, Y in formula (I) can be a hydrophobic moiety, at least 50% of which are selected from I, V, L, F, C, M, and A. In some embodiments, Y in formula (I) can be a hydrophobic moiety, at least 55% of which are selected from I, V, L, F, C, M, and A. In some embodiments, Y in formula (I) can be a hydrophobic moiety, at least 60% of which are selected from I, V, L, F, C, M, and A. In some embodiments, Y in formula (I) can be a hydrophobic moiety, at least 65% of which are selected from I, V, L, F, C, M, and A. In some embodiments, Y in formula (I) can be a hydrophobic moiety, at least 70% of which are selected from I, V, L, F, C, M, and A. In some embodiments, Y in formula (I) can be a hydrophobic moiety, at least 75% of which are selected from I, V, L, F, C, M, and A. In some embodiments, Y in formula (I) can be a hydrophobic moiety, at least 80% of which are selected from I, V, L, F, C, M, and A. In some embodiments, Y in formula (I) can be a hydrophobic moiety, at least 85% of which are selected from I, V, L, F, C, M, and A. In some embodiments, Y in formula (I) can be a hydrophobic moiety, at least 90% of which are selected from I, V, L, F, C, M, and A.

[0123] In some embodiments, Y in formula (I) can be a moiety containing 10 to 50 amino acids, and the total number of hydrophobic amino acids in Y is 5. In some embodiments, Y in formula (I) can be a moiety 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) can be a moiety 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) can be a moiety 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) can be a moiety 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) can be a moiety 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) can be a moiety 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) can be a moiety comprising 10 to 50 amino acids, wherein the total number of hydrophobic amino acids in Y is greater than 8. In some embodiments, Y in formula (I) can be a moiety comprising 10 to 50 amino acids, wherein the total number of hydrophobic amino acids in Y is 9. In some embodiments, Y in formula (I) can be a moiety comprising 10 to 50 amino acids, wherein the total number of hydrophobic amino acids in Y is greater than 9. In some embodiments, Y in formula (I) can be a moiety comprising 10 to 50 amino acids, wherein the total number of hydrophobic amino acids in Y is 10. In some embodiments, Y in formula (I) can be a moiety comprising 10 to 50 amino acids, wherein the total number of hydrophobic amino acids in Y is greater than 10. In some embodiments, Y in formula (I) can be a moiety comprising 10 to 50 amino acids, wherein the total number of hydrophobic amino acids in Y is 11. In some embodiments, Y in formula (I) can be a moiety comprising 10 to 50 amino acids, wherein the total number of hydrophobic amino acids in Y is greater than 11. In some embodiments, Y of formula (I) can be a moiety comprising 10-50 amino acids, wherein the total number of hydrophobic amino acids in Y is 12. In some embodiments, Y of formula (I) can be a moiety comprising 10-50 amino acids, wherein the total number of hydrophobic amino acids in Y is greater than 12. In some embodiments, Y of formula (I) can be a moiety comprising 10-50 amino acids, wherein the total number of hydrophobic amino acids in Y is 13.In some embodiments, Y in formula (I) can be a moiety comprising 10 to 50 amino acids, wherein the total number of hydrophobic amino acids in Y is greater than 13. In some embodiments, Y in formula (I) can be a moiety comprising 10 to 50 amino acids, wherein the total number of hydrophobic amino acids in Y is 14. In some embodiments, Y in formula (I) can be a moiety comprising 10 to 50 amino acids, wherein the total number of hydrophobic amino acids in Y is greater than 14. In some embodiments, Y in formula (I) can be a moiety comprising 10 to 50 amino acids, wherein the total number of hydrophobic amino acids in Y is 15. In some embodiments, Y in formula (I) can be a moiety comprising 10 to 50 amino acids, wherein the total number of hydrophobic amino acids in Y is greater than 15.

[0124] In some embodiments, Y in formula (I) can be a moiety comprising 10 to 50 amino acids, wherein the total number of I, V, L, F, C, M, and A in Y is 5. In some embodiments, Y in formula (I) can be a moiety comprising 10 to 50 amino acids, wherein 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) can be a moiety comprising 10 to 50 amino acids, wherein the total number of I, V, L, F, C, M, and A in Y is 6. In some embodiments, Y in formula (I) can be a moiety comprising 10 to 50 amino acids, wherein 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) can be a moiety comprising 10 to 50 amino acids, wherein the total number of I, V, L, F, C, M, and A in Y is 7. In some embodiments, Y in formula (I) can be a moiety comprising 10 to 50 amino acids, wherein 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) can be a moiety comprising 10 to 50 amino acids, wherein the total number of I, V, L, F, C, M, and A in Y is 8. In some embodiments, Y in formula (I) can be a moiety comprising 10 to 50 amino acids, wherein 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) can be a moiety comprising 10 to 50 amino acids, wherein the total number of I, V, L, F, C, M, and A in Y is 9. In some embodiments, Y in formula (I) can be a moiety comprising 10 to 50 amino acids, wherein 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) can be a moiety comprising 10 to 50 amino acids, wherein the total number of I, V, L, F, C, M, and A in Y is 10. In some embodiments, Y in formula (I) can be a moiety comprising 10 to 50 amino acids, wherein 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) can be a moiety comprising 10 to 50 amino acids, wherein the total number of I, V, L, F, C, M, and A in Y is 11. In some embodiments, Y in formula (I) can be a moiety comprising 10 to 50 amino acids, wherein 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) can be a moiety comprising 10 to 50 amino acids, wherein the total number of I, V, L, F, C, M, and A in Y is 12.In some embodiments, Y in formula (I) can be a moiety comprising 10 to 50 amino acids, wherein 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) can be a moiety comprising 10 to 50 amino acids, wherein the total number of I, V, L, F, C, M, and A in Y is 13. In some embodiments, Y in formula (I) can be a moiety comprising 10 to 50 amino acids, wherein 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) can be a moiety comprising 10 to 50 amino acids, wherein the total number of I, V, L, F, C, M, and A in Y is 14. In some embodiments, Y in formula (I) can be a moiety comprising 10 to 50 amino acids, wherein the total number of I, V, L, F, C, M, and A in Y is greater than 14. In some embodiments, Y of formula (I) can be a moiety comprising 10-50 amino acids, and the total number of I, V, L, F, C, M, and A in Y is 15. In some embodiments, Y of formula (I) can be a moiety comprising 10-50 amino acids, and the total number of I, V, L, F, C, M, and A in Y is greater than 15.

[0125] In some embodiments, Y in formula (I) can be a moiety comprising 10 to 50 amino acids, and the total number of cysteines (C) in Y is 5. In some embodiments, Y in formula (I) can be a moiety comprising 10 to 50 amino acids, and the total number of cysteines (C) in Y is less than 5. In some embodiments, Y in formula (I) can be a moiety comprising 10 to 50 amino acids, and the total number of cysteines (C) in Y is 4. In some embodiments, Y in formula (I) can be a moiety comprising 10 to 50 amino acids, and the total number of cysteines (C) in Y is less than 4. In some embodiments, Y in formula (I) can be a moiety comprising 10 to 50 amino acids, and the total number of cysteines (C) in Y is 3. In some embodiments, Y in formula (I) can be a moiety comprising 10 to 50 amino acids, and the total number of cysteines (C) in Y is less than 3. In some embodiments, Y in formula (I) can be a moiety comprising 10 to 50 amino acids, and the total number of cysteines (C) in Y is 2. In some embodiments, Y in formula (I) can be a moiety comprising 10 to 50 amino acids, and the total number of cysteines (C) in Y is less than 2. In some embodiments, Y in formula (I) can be a moiety comprising 10 to 50 amino acids, and the total number of cysteines (C) in Y is 1. In some embodiments, Y in formula (I) can be a moiety comprising 10 to 50 amino acids, and the total number of cysteines (C) in Y is less than 1. In some embodiments, Y in formula (I) can be a moiety comprising 10 to 50 amino acids, and the total number of cysteines (C) in Y is 0.

[0126] 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 5 or less. 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 4 or less. 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 3 or less. 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 2 or less. 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 1 or less.

[0127] 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 5 or less. 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 4 or less. 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 3 or less. 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 2 or less. 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 1 or less.

[0128] In some embodiments of the artificial polypeptide, X in Formula (I) comprises a sequence at least 70% identical to any one of SEQ ID NOs: 81-83. In some embodiments of the artificial polypeptide, X in Formula (I) comprises a sequence at least 75% identical to any one of SEQ ID NOs: 81-83. In some embodiments of the artificial polypeptide, X in Formula (I) comprises a sequence at least 80% identical to any one of SEQ ID NOs: 81-83. In some embodiments of the artificial polypeptide, X in Formula (I) comprises a sequence at least 85% identical to any one of SEQ ID NOs: 81-83. In some embodiments of the artificial polypeptide, X in Formula (I) comprises a sequence at least 90% identical to any one of SEQ ID NOs: 81-83. In some embodiments of the artificial polypeptide, X in Formula (I) comprises a sequence at least 95% identical to any one of SEQ ID NOs: 81-83. In some embodiments of the artificial polypeptide, X of Formula (I) comprises a sequence having 96%, at least 97%, at least 98%, or at least 99% identity to any one selected from SEQ ID NOs: 81-83. In some embodiments of the artificial polypeptide, X of Formula (I) comprises any one sequence selected from SEQ ID NOs: 81-83. In some embodiments of the artificial polypeptide, X of Formula (I) is any one sequence selected from SEQ ID NOs: 81-83.

[0129] In some embodiments of the artificial polypeptide, Y of Formula (I) comprises a sequence having at least 70% identity to any one selected from SEQ ID NOs: 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 to any one selected from SEQ ID NOs: 3-15, 58-61, and 84-85. In some embodiments of the artificial polypeptide, Y of Formula (I) comprises a sequence having at least 80% identity to any one selected from SEQ ID NOs: 3-15, 58-61, and 84-85. In some embodiments of the artificial polypeptide, Y of Formula (I) comprises a sequence having at least 85% identity to any one selected from SEQ ID NOs: 3-15, 58-61, and 84-85. In some embodiments of the artificial polypeptide, Y of Formula (I) comprises a sequence having at least 90% identity to any one selected from SEQ ID NOs: 3-15, 58-61, and 84-85. In some embodiments of the artificial polypeptide, Y of Formula (I) comprises a sequence having at least 95% identity to any one selected from SEQ ID NOs: 3-15, 58-61, and 84-85. In some embodiments of the artificial polypeptide, Y of Formula (I) comprises a sequence having 96%, at least 97%, at least 98%, or at least 99% identity to any one selected from SEQ ID NOs: 3-15, 58-61, and 84-85. In some embodiments of the artificial polypeptide, Y of Formula (I) comprises a sequence selected from SEQ ID NOs: 3-15, 58-61, and 84-85. In some embodiments of the artificial polypeptide, Y of Formula (I) is any one sequence selected from SEQ ID NOs: 3-15, 58-61, and 84-85.

[0130] In some embodiments of an artificial polypeptide of Formula (I), the polypeptide comprises a sequence having at least 70% identity to any one selected from SEQ ID NOs: 29-41, 54-57, 75, and 91-95. In some embodiments of an artificial polypeptide of Formula (I), the polypeptide comprises a sequence having at least 75% identity to any one selected from SEQ ID NOs: 29-41, 54-57, 75, and 91-95. In some embodiments of an artificial polypeptide of Formula (I), the polypeptide comprises a sequence having at least 80% identity to any one selected from SEQ ID NOs: 29-41, 54-57, 75, and 91-95. In some embodiments of an artificial polypeptide of Formula (I), the polypeptide comprises a sequence having at least 85% identity to any one selected from SEQ ID NOs: 29-41, 54-57, 75, and 91-95. In some embodiments of an artificial polypeptide of Formula (I), the polypeptide comprises a sequence at least 90% identical to any one selected from SEQ ID NOs: 29-41, 54-57, 75, and 91-95. In some embodiments of an artificial polypeptide of Formula (I), the polypeptide comprises a sequence at least 95% identical to any one selected from SEQ ID NOs: 29-41, 54-57, 75, and 91-95. In some embodiments of an artificial polypeptide of Formula (I), the polypeptide comprises a sequence at least 96%, at least 97%, at least 98%, or at least 99% identical to any one selected from SEQ ID NOs: 29-41, 54-57, 75, and 91-95. In some embodiments of an artificial polypeptide of Formula (I), the polypeptide comprises a sequence at least 96%, at least 97%, at least 98%, or at least 99% identical to any one selected from SEQ ID NOs: 29-41, 54-57, 75, and 91-95. In some embodiments of the artificial polypeptide of Formula (I), the polypeptide is any one of SEQ ID NOs: 29-41, 54-57, 75, and 91-95.

[0131] In another aspect, a method is provided for treating or preventing allergic conjunctivitis in a subject in need thereof, comprising administering an effective amount of an artificial polypeptide of formula (II): XY(II) administering to a subject: X is a portion containing a sequence having at least 80% identity with 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 having at most 90% identity to SEQ ID NO:2.

[0132] In some embodiments, X in formula (II) can be a hydrophilic moiety, at least 50% of which are selected from R, K, N, D, Q, E, and H. In some embodiments, X in formula (II) can be a hydrophilic moiety, at least 55% of which are selected from R, K, N, D, Q, E, and H. In some embodiments, X in formula (I) can be a hydrophilic moiety, at least 60% of which are selected from R, K, N, D, Q, E, and H. In some embodiments, X in formula (II) can be a hydrophilic moiety, at least 65% of which are selected from R, K, N, D, Q, E, and H. In some embodiments, X in formula (II) can be a hydrophilic moiety, at least 70% of which are selected from R, K, N, D, Q, E, and H. In some embodiments, X in (II) can be a hydrophilic moiety, at least 75% of which are selected from R, K, N, D, Q, E, and H. In some embodiments, X in formula (II) can be a hydrophilic moiety, at least 80% of which are selected from R, K, N, D, Q, E, and H. In some embodiments, X in formula (II) can be a hydrophilic moiety, at least 85% of which are selected from R, K, N, D, Q, E, and H. In some embodiments, X in formula (II) can be a hydrophilic moiety, at least 90% of which are selected from R, K, N, D, Q, E, and H.

[0133] In some embodiments, X in Formula (II) can be a hydrophilic moiety comprising one or more arginines (R). 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 arginines (R). In some embodiments, X in Formula (II) can 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 lysines (K). In some embodiments, X in Formula (II) can be a hydrophilic moiety comprising one or more asparagines (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 asparagines (N). In some embodiments, X in Formula (II) can be a hydrophilic moiety comprising one or more aspartic acids (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 acids (D). In some embodiments, X in Formula (II) can be a hydrophilic moiety comprising one or more glutamines (Q). 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 glutamines (Q). In some embodiments, X in formula (II) can be a hydrophilic moiety that includes one or more glutamic acids (E).For example, X in Formula (II) can be a hydrophilic moiety that includes 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 in Formula (II) can be a hydrophilic moiety that includes one or more histidines (H). For example, X in Formula (II) can be a hydrophilic moiety that includes 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).

[0134] In some embodiments, X in formula (II) can be a moiety comprising a sequence having at least 80% identity to SEQ ID NO:1. In some embodiments, X is a moiety comprising a sequence having at least 85% identity to SEQ ID NO:1. In some embodiments, X is a moiety comprising a sequence having at least 90% identity to SEQ ID NO:1. In some embodiments, X is a moiety comprising a sequence having at least 95% identity to SEQ ID NO:1. In some embodiments, X is a moiety comprising a sequence having at least 96%, at least 97%, at least 98%, or at least 99% identity to SEQ ID NO:1. In some embodiments, X is a moiety comprising the sequence of SEQ ID NO:1. In some embodiments, X is a moiety that is the sequence of SEQ ID NO:1.

[0135] In some embodiments of an artificial polypeptide of Formula (II), Y comprises a sequence that is at most 50% identical to SEQ ID NO:2. In some embodiments, Y comprises a sequence that is at most 55% identical to SEQ ID NO:2. In some embodiments, Y comprises a sequence that is at most 60% identical to SEQ ID NO:2. In some embodiments, Y comprises a sequence that is at most 65% identical to SEQ ID NO:2. In some embodiments, Y comprises a sequence that is at most 70% identical to SEQ ID NO:2. In some embodiments, Y comprises a sequence that is at most 75% identical to SEQ ID NO:2. In some embodiments, Y comprises a sequence that is at most 80% identical to SEQ ID NO:2. In some embodiments, Y comprises a sequence that is at most 85% identical to SEQ ID NO:2. In some embodiments, Y comprises a sequence that is at most 90% identical to SEQ ID NO:2.

[0136] In some embodiments of an artificial polypeptide of Formula (II), Y comprises a sequence at least 70% identical to any one of SEQ ID NOs: 16-18. In some embodiments of an artificial polypeptide, Y comprises a sequence at least 75% identical to any one of SEQ ID NOs: 16-18. In some embodiments of an artificial polypeptide, Y comprises a sequence at least 80% identical to any one of SEQ ID NOs: 16-18. In some embodiments of an artificial polypeptide, Y comprises a sequence at least 85% identical to any one of SEQ ID NOs: 16-18. In some embodiments of an artificial polypeptide, Y comprises a sequence at least 90% identical to any one of SEQ ID NOs: 16-18. In some embodiments of an artificial polypeptide, Y comprises a sequence at least 95% identical to any one of SEQ ID NOs: 16-18. In some embodiments of the artificial polypeptide, Y comprises a sequence having 96%, at least 97%, at least 98%, or at least 99% identity to any one selected from SEQ ID NOs: 16-18. In some embodiments of the artificial polypeptide, Y comprises any one sequence selected from SEQ ID NOs: 16-18. In some embodiments of the artificial polypeptide, Y is any one sequence selected from SEQ ID NOs: 16-18.

[0137] In some embodiments of an artificial polypeptide of Formula (II), the artificial polypeptide comprises a sequence at least 70% identical to any one of SEQ ID NOs: 42-44. In some embodiments of an artificial polypeptide, the artificial polypeptide comprises a sequence at least 75% identical to any one of SEQ ID NOs: 42-44. In some embodiments of an artificial polypeptide, the artificial polypeptide comprises a sequence at least 80% identical to any one of SEQ ID NOs: 42-44. In some embodiments of an artificial polypeptide, the artificial polypeptide comprises a sequence at least 85% identical to any one of SEQ ID NOs: 42-44. In some embodiments of an artificial polypeptide, the artificial polypeptide comprises a sequence at least 90% identical to any one of SEQ ID NOs: 42-44. In some embodiments of an artificial polypeptide, the artificial polypeptide comprises a sequence at least 95% identical to any one of SEQ ID NOs: 42-44. In some embodiments of the artificial polypeptide, the artificial polypeptide comprises a sequence having 96%, at least 97%, at least 98%, or at least 99% identity to any one selected from SEQ ID NOs: 42-44. In some embodiments of the artificial polypeptide, the artificial polypeptide comprises any one sequence selected from SEQ ID NOs: 42-44. In some embodiments of the artificial polypeptide, the artificial polypeptide is any one sequence selected from SEQ ID NOs: 42-44.

[0138] In another aspect, a method is provided for treating or preventing allergic conjunctivitis in a subject in need thereof, comprising administering an effective amount of an artificial polypeptide of formula (III): XY(III) administering to a subject: 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 portion containing 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.

[0139] In some embodiments, X in Formula (III) can be a hydrophilic moiety, at least 50% of which are selected from H, R, K, D, Q, N, and E. In some embodiments, X in Formula (III) can be a hydrophilic moiety, at least 55% of which are selected from R, K, N, D, Q, E, and H. In some embodiments, X in Formula (III) can be a hydrophilic moiety, at least 60% of which are selected from R, K, N, D, Q, E, and H. In some embodiments, X in Formula (III) can be a hydrophilic moiety, at least 65% of which are selected from R, K, N, D, Q, E, and H. In some embodiments, X in Formula (III) can be a hydrophilic moiety, at least 70% of which are selected from R, K, N, D, Q, E, and H. In some embodiments, X in Formula (III) can be a hydrophilic moiety, at least 75% of which are selected from R, K, N, D, Q, E, and H. In some embodiments, X in formula (III) can be a hydrophilic moiety, at least 80% of which are selected from R, K, N, D, Q, E, and H. In some embodiments, X in formula (III) can be a hydrophilic moiety, at least 85% of which are selected from R, K, N, D, Q, E, and H. In some embodiments, X in formula (III) can be a hydrophilic moiety, at least 90% of which are selected from R, K, N, D, Q, E, and H.

[0140] In some embodiments, X in formula (III) is a moiety 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 in formula (III) is a moiety 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 formula (III) is a moiety 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 formula (III) is a moiety 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 formula (III) is a moiety 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 formula (III) is a moiety 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 formula (III) is a moiety 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 formula (III) is a moiety 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 formula (III) is a moiety 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 formula (III) is a moiety 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 formula (III) is a moiety comprising 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 formula (III) is a moiety comprising 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, X in formula (III) is a moiety comprising 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 formula (III) is a moiety comprising 40 to 65 amino acids, and the total number of H, R, K, D, Q, N, and E in X is less than 20.

[0141] In some embodiments, X in formula (III) is a moiety 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 formula (III) is a moiety 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 formula (III) is a moiety 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 formula (III) is a moiety 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 formula (III) is a moiety 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 formula (III) is a moiety 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 formula (III) is a moiety 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 formula (III) is a moiety 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 formula (III) is a moiety 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 formula (III) is a moiety 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 formula (III) is a moiety 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 formula (III) is a moiety 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 formula (III) is a moiety 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 formula (III) is a moiety 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 moiety comprising 40-65 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 moiety comprising 40-65 amino acids, and the total number of hydrophilic amino acids in X is greater than 25.

[0142] In some embodiments, X in formula (III) is a moiety containing 40 to 65 amino acids, and the total number of hydrophobic amino acids in X is 15 or less. In some embodiments, X in formula (III) is a moiety containing 40 to 65 amino acids, and the total number of hydrophobic amino acids in X is 14 or less. In some embodiments, X in formula (III) is a moiety containing 40 to 65 amino acids, and the total number of hydrophobic amino acids in X is 13 or less. In some embodiments, X in formula (III) is a moiety containing 40 to 65 amino acids, and the total number of hydrophobic amino acids in X is 12 or less. In some embodiments, X in formula (III) is a moiety containing 40 to 65 amino acids, and the total number of hydrophobic amino acids in X is 11 or less. In some embodiments, X in formula (III) is a moiety containing 40 to 65 amino acids, and the total number of hydrophobic amino acids in X is 10 or less. In some embodiments, X in formula (III) is a moiety containing 40 to 65 amino acids, and the total number of hydrophobic amino acids in X is 5 or less.

[0143] In some embodiments, X in formula (III) comprises a sequence having at least 70% identity to any one selected from SEQ ID NOs: 23-27. In some embodiments, X in formula (III) comprises a sequence having at least 75% identity to any one selected from SEQ ID NOs: 23-27. In some embodiments, X in formula (III) comprises a sequence having at least 80% identity to any one selected from SEQ ID NOs: 23-27. In some embodiments, X in formula (III) comprises a sequence having at least 85% identity to any one selected from SEQ ID NOs: 23-27. In some embodiments, X in formula (III) comprises a sequence having at least 90% identity to any one selected from SEQ ID NOs: 23-27. In some embodiments, X in formula (III) comprises a sequence having at least 95% identity to any one selected from SEQ ID NOs: 23-27. In some embodiments, X in formula (III) comprises a sequence having 96%, at least 97%, at least 98%, or at least 99% identity to any one selected from SEQ ID NOs: 23 to 27. In some embodiments, X in formula (III) comprises any one sequence selected from SEQ ID NOs: 23 to 27. In some embodiments, X in formula (III) is any one sequence selected from SEQ ID NOs: 23 to 27.

[0144] In some embodiments, Y in formula (III) is a moiety comprising a sequence having at least 70% identity to SEQ ID NO:2. In some embodiments, Y in formula (III) is a moiety comprising a sequence having at least 75% identity to SEQ ID NO:2. In some embodiments, Y in formula (III) is a moiety comprising a sequence having at least 80% identity to SEQ ID NO:2. In some embodiments, Y in formula (III) is a moiety comprising a sequence having at least 85% identity to SEQ ID NO:2. In some embodiments, Y in formula (III) is a moiety comprising a sequence having at least 90% identity to SEQ ID NO:2. In some embodiments, Y in formula (III) is a moiety comprising a sequence having at least 95% identity to SEQ ID NO:2. In some embodiments, Y in formula (III) is a moiety comprising a sequence having at least 96%, at least 97%, at least 98%, or at least 99% identity to SEQ ID NO:2. In some embodiments, Y in formula (III) is a moiety comprising the sequence of SEQ ID NO:2. In some embodiments, Y in formula (III) is a moiety that is the sequence of SEQ ID NO:2.

[0145] In some embodiments, Y of formula (III) is a hydrophobic moiety, and at least 50% of the amino acids of Y are selected from I, V, L, F, C, M, and A. In some embodiments, Y of formula (III) is a hydrophobic moiety, and at least 55% of the amino acids of Y are selected from I, V, L, F, C, M, and A. In some embodiments, Y of formula (III) is a hydrophobic moiety, and at least 60% of the amino acids of Y are selected from I, V, L, F, C, M, and A. In some embodiments, Y of formula (III) is a hydrophobic moiety, and at least 65% of the amino acids of Y are selected from I, V, L, F, C, M, and A. In some embodiments, Y of formula (III) is a hydrophobic moiety, and at least 70% of the amino acids of Y are selected from I, V, L, F, C, M, and A. In some embodiments, Y of formula (III) is a hydrophobic moiety and at least 75% of the amino acids of Y are selected from I, V, L, F, C, M, and A. In some embodiments, Y of formula (III) is a hydrophobic moiety and at least 80% of the amino acids of Y are selected from I, V, L, F, C, M, and A. In some embodiments, Y of formula (III) is a hydrophobic moiety and at least 85% of the amino acids of Y are selected from I, V, L, F, C, M, and A. In some embodiments, Y of formula (III) is a hydrophobic moiety and at least 90% of the amino acids of Y are selected from I, V, L, F, C, M, and A.

[0146] In some embodiments, an artificial polypeptide of Formula (III) comprises a sequence at least 70% identical to any one of SEQ ID NOs: 49-53. In some embodiments, an artificial polypeptide of Formula (III) comprises a sequence at least 75% identical to any one of SEQ ID NOs: 49-53. In some embodiments, an artificial polypeptide of Formula (III) comprises a sequence at least 80% identical to any one of SEQ ID NOs: 49-53. In some embodiments, an artificial polypeptide of Formula (III) comprises a sequence at least 85% identical to any one of SEQ ID NOs: 49-53. In some embodiments, an artificial polypeptide of Formula (III) comprises a sequence at least 90% identical to any one of SEQ ID NOs: 49-53. In some embodiments, an artificial polypeptide of Formula (III) comprises a sequence at least 95% identical to any one of SEQ ID NOs: 49-53. In some embodiments, the artificial polypeptide of Formula (III) comprises a sequence having 96%, at least 97%, at least 98%, or at least 99% identity to any one of SEQ ID NOs: 49-53. In some embodiments, the artificial polypeptide of Formula (III) comprises any one of SEQ ID NOs: 49-53. In some embodiments, the artificial polypeptide of Formula (III) is any one of SEQ ID NOs: 49-53.

[0147] In another aspect, a method is provided for treating or preventing allergic conjunctivitis in a subject in need thereof, comprising administering an effective amount of an artificial polypeptide of formula (IV): XY(IV) administering to a subject: 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 portion containing a sequence having at least 80% identity with SEQ ID NO: 2, X comprises a sequence having at most 90% identity to SEQ ID NO:1.

[0148] In some embodiments, X in formula (IV) can be a hydrophilic moiety, at least 50% of which are selected from H, R, K, D, Q, N, and E. In some embodiments, X in formula (IV) can be a hydrophilic moiety, at least 55% of which are selected from R, K, N, D, Q, E, and H. In some embodiments, X in formula (IV) can be a hydrophilic moiety, at least 60% of which are selected from R, K, N, D, Q, E, and H. In some embodiments, X in formula (IV) can be a hydrophilic moiety, at least 65% of which are selected from R, K, N, D, Q, E, and H. In some embodiments, X in formula (IV) can be a hydrophilic moiety, at least 70% of which are selected from R, K, N, D, Q, E, and H. In some embodiments, X in formula (IV) can be a hydrophilic moiety, at least 75% of which are selected from R, K, N, D, Q, E, and H. In some embodiments, X in formula (IV) can be a hydrophilic moiety, at least 80% of which are selected from R, K, N, D, Q, E, and H. In some embodiments, X in formula (IV) can be a hydrophilic moiety, at least 85% of which are selected from R, K, N, D, Q, E, and H. In some embodiments, X in formula (IV) can be a hydrophilic moiety, at least 90% of which are selected from R, K, N, D, Q, E, and H.

[0149] In some embodiments, X in 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 in 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 in 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 in 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 in 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 in formula (IV) comprises 40 to 65 amino acids, and the total number of hydrophilic amino acids in X is greater than 35.

[0150] In some embodiments, X of formula (IV) comprises a sequence having at most 50% identity to SEQ ID NO:1. In some embodiments, X of formula (IV) comprises a sequence having at most 55% identity to SEQ ID NO:1. In some embodiments, X of formula (IV) comprises a sequence having at most 60% identity to SEQ ID NO:1. In some embodiments, X of formula (IV) comprises a sequence having at most 65% identity to SEQ ID NO:1. In some embodiments, X of formula (IV) comprises a sequence having at most 70% identity to SEQ ID NO:1. In some embodiments, X of formula (IV) comprises a sequence having at most 75% identity to SEQ ID NO:1. In some embodiments, X of formula (IV) comprises a sequence having at most 80% identity to SEQ ID NO:1. In some embodiments, X of formula (IV) comprises a sequence having at most 85% identity to SEQ ID NO:1. In some embodiments, X of formula (IV) comprises a sequence having at most 90% identity to SEQ ID NO:1.

[0151] In some embodiments, Y in formula (IV) is a moiety comprising a sequence having at least 70% identity to SEQ ID NO:2. In some embodiments, Y in formula (IV) is a moiety comprising a sequence having at least 75% identity to SEQ ID NO:2. In some embodiments, Y in formula (IV) is a moiety comprising a sequence having at least 80% identity to SEQ ID NO:2. In some embodiments, Y in formula (IV) is a moiety comprising a sequence having at least 85% identity to SEQ ID NO:2. In some embodiments, Y in formula (IV) is a moiety comprising a sequence having at least 90% identity to SEQ ID NO:2. In some embodiments, Y in formula (IV) is a moiety comprising a sequence having at least 95% identity to SEQ ID NO:2. In some embodiments, Y in formula (IV) is a moiety comprising a sequence having at least 96%, at least 97%, at least 98%, or at least 99% identity to SEQ ID NO:2. In some embodiments, Y in formula (IV) is a moiety comprising the sequence of SEQ ID NO:2. In some embodiments, Y in formula (IV) is a moiety that is the sequence of SEQ ID NO:2.

[0152] In some embodiments, Y in formula (IV) is a hydrophobic moiety, 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 moiety, 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 moiety, 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 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 (IV) 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 (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.

[0153] In some embodiments, X in formula (IV) comprises a sequence having at least 70% identity to any one selected from SEQ ID NOs: 19-22 and 76-79. In some embodiments, X in formula (IV) comprises a sequence having at least 75% identity to any one selected from SEQ ID NOs: 19-22 and 76-79. In some embodiments, X in formula (IV) comprises a sequence having at least 80% identity to any one selected from SEQ ID NOs: 19-22 and 76-79. In some embodiments, X in formula (IV) comprises a sequence having at least 85% identity to any one selected from SEQ ID NOs: 19-22 and 76-79. In some embodiments, X in formula (IV) comprises a sequence having at least 90% identity to any one selected from SEQ ID NOs: 19-22 and 76-79. In some embodiments, X in formula (IV) comprises a sequence having at least 95% identity to any one selected from SEQ ID NOs: 19-22 and 76-79. In some embodiments, X in formula (IV) comprises a sequence having 96%, at least 97%, at least 98%, or at least 99% identity to any one selected from SEQ ID NOs: 19-22 and 76-79. In some embodiments, X in formula (IV) comprises any one sequence selected from SEQ ID NOs: 19-22 and 76-79. In some embodiments, X in formula (IV) is any one sequence selected from SEQ ID NOs: 19-22 and 76-79.

[0154] In some embodiments, an artificial polypeptide of Formula (IV) comprises a sequence at least 70% identical to any one of SEQ ID NOs: 45-48 and 86-89. In some embodiments, an artificial polypeptide of Formula (IV) comprises a sequence at least 75% identical to any one of SEQ ID NOs: 45-48 and 86-89. In some embodiments, an artificial polypeptide of Formula (IV) comprises a sequence at least 80% identical to any one of SEQ ID NOs: 45-48 and 86-89. In some embodiments, an artificial polypeptide of Formula (IV) comprises a sequence at least 85% identical to any one of SEQ ID NOs: 45-48 and 86-89. In some embodiments, an artificial polypeptide of Formula (IV) comprises a sequence at least 90% identical to any one of SEQ ID NOs: 45-48 and 86-89. In some embodiments, an artificial polypeptide of Formula (IV) comprises a sequence at least 95% identical to any one of SEQ ID NOs: 45-48 and 86-89. In some embodiments, the artificial polypeptide of Formula (IV) comprises a sequence having 96%, at least 97%, at least 98%, or at least 99% identity to any one selected from SEQ ID NOs: 45-48 and 86-89. In some embodiments, the artificial polypeptide of Formula (IV) comprises any one sequence selected from SEQ ID NOs: 45-48 and 86-89. In some embodiments, the artificial polypeptide of Formula (IV) is any one sequence selected from SEQ ID NOs: 45-48 and 86-89.

[0155] In another aspect, a method is provided for treating or preventing allergic conjunctivitis in a subject in need thereof, comprising administering an effective amount of an artificial polypeptide of formula (V): XY(V) administering to a subject: X is a portion containing a sequence having at least 80% identity with SEQ ID NO: 1; Y is a moiety containing 10 to 30 amino acids, and Y includes a sequence having at least 10 consecutive AA of SEQ ID NO:2.

[0156] 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.

[0157] In some embodiments, X in formula (V) can be a moiety comprising a sequence having at least 80% identity to SEQ ID NO:1. In some embodiments, X is a moiety comprising a sequence having at least 85% identity to SEQ ID NO:1. In some embodiments, X is a moiety comprising a sequence having at least 90% identity to SEQ ID NO:1. In some embodiments, X is a moiety comprising a sequence having at least 95% identity to SEQ ID NO:1. In some embodiments, X is a moiety comprising a sequence having at least 96%, at least 97%, at least 98%, or at least 99% identity to SEQ ID NO:1. In some embodiments, X is a moiety comprising the sequence of SEQ ID NO:1. In some embodiments, X is a moiety that is the sequence of SEQ ID NO:1.

[0158] In some embodiments of an 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.

[0159] In some embodiments of an artificial polypeptide of Formula (V), X comprises a sequence having at least 70% identity to SEQ ID NO:96. In some embodiments of an artificial polypeptide of Formula (V), X comprises a sequence having at least 75% identity to SEQ ID NO:96. In some embodiments of an artificial polypeptide of Formula (V), X comprises a sequence having at least 80% identity to SEQ ID NO:96. In some embodiments, X comprises a sequence having at least 85% identity to SEQ ID NO:96. In some embodiments, X comprises a sequence having at least 90% identity to SEQ ID NO:96. In some embodiments, X comprises a sequence having at least 95% identity to 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 to 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.

[0160] In some embodiments of an artificial polypeptide of Formula (V), Y comprises a sequence that is at most 50% identical to SEQ ID NO:2. In some embodiments, Y comprises a sequence that is at most 55% identical to SEQ ID NO:2. In some embodiments, Y comprises a sequence that is at most 60% identical to SEQ ID NO:2. In some embodiments, Y comprises a sequence that is at most 65% identical to SEQ ID NO:2. In some embodiments, Y comprises a sequence that is at most 70% identical to SEQ ID NO:2. In some embodiments, Y comprises a sequence that is at most 75% identical to SEQ ID NO:2. In some embodiments, Y comprises a sequence that is at most 80% identical to SEQ ID NO:2. In some embodiments, Y comprises a sequence that is at most 85% identical to SEQ ID NO:2. In some embodiments, Y comprises a sequence that is at most 90% identical to SEQ ID NO:2.

[0161] In some embodiments of an artificial polypeptide of Formula (V), Y comprises a sequence at least 70% identical to any one of SEQ ID NOs: 97-103. In some embodiments of an artificial polypeptide of Formula (V), Y comprises a sequence at least 75% identical to any one of SEQ ID NOs: 97-103. In some embodiments of an artificial polypeptide of Formula (V), Y comprises a sequence at least 80% identical to any one of SEQ ID NOs: 97-103. In some embodiments, Y comprises a sequence at least 85% identical to any one of SEQ ID NOs: 97-103. In some embodiments, Y comprises a sequence at least 90% identical to any one of SEQ ID NOs: 97-103. In some embodiments, Y comprises a sequence at least 95% identical to any one of SEQ ID NOs: 97-103. In some embodiments, Y comprises a sequence having 96%, at least 97%, at least 98%, or at least 99% identity to any one selected from SEQ ID NOs: 97-103. In some embodiments, Y comprises a sequence that is any one selected from SEQ ID NOs: 97-103. In some embodiments, Y is a sequence that is any one selected from SEQ ID NOs: 97-103.

[0162] In some embodiments, an artificial polypeptide of Formula (V) comprises a sequence at least 70% identical to any one selected from SEQ ID NOs: 53-56 and 104-110. In some embodiments, an artificial polypeptide of Formula (V) comprises a sequence at least 75% identical to any one selected from SEQ ID NOs: 53-56 and 104-110. In some embodiments, an artificial polypeptide of Formula (V) comprises a sequence at least 80% identical to any one selected from SEQ ID NOs: 53-56 and 104-110. In some embodiments, an artificial polypeptide of Formula (V) comprises a sequence at least 85% identical to any one selected from SEQ ID NOs: 53-56 and 104-110. In some embodiments, an artificial polypeptide of Formula (V) comprises a sequence at least 90% identical to any one selected from SEQ ID NOs: 53-56 and 104-110. In some embodiments, an artificial polypeptide of Formula (V) comprises a sequence having at least 95% identity to any one selected from SEQ ID NOs: 53-56 and 104-110. In some embodiments, an artificial polypeptide of Formula (V) comprises a sequence having 96%, at least 97%, at least 98%, or at least 99% identity to any one selected from SEQ ID NOs: 53-56 and 104-110. In some embodiments, an artificial polypeptide of Formula (V) comprises a sequence selected from SEQ ID NOs: 53-56 and 104-110. In some embodiments, an artificial polypeptide of Formula (V) is any one sequence selected from SEQ ID NOs: 53-56 and 104-110.

[0163] In another aspect, a method is provided for treating or preventing allergic conjunctivitis in a subject in need thereof, comprising administering an effective amount of an artificial polypeptide of formula (VI): XY(VI) administering to a subject: X is a moiety comprising a variant of SEQ ID NO: 1, wherein the variant is characterized in that at least 1, 2, 3, 4, 5, 6, 7, 8, or 9 Ds in SEQ ID NO: 1 are mutated to S, and / or at least 1, 2, 3, 4, 5, or 6 Es in SEQ ID NO: 1 are mutated to T; Y is a moiety comprising a variant of SEQ ID NO:2, wherein the variant is characterized by at least 1, 2, 3, 4, or 5 C's in SEQ ID NO:2 being mutated to A's.

[0164] In some embodiments, X of formula (VI) comprises a sequence having at least 70% identity to SEQ ID NO:1. In some embodiments, X of formula (VI) comprises a sequence having at least 75% identity to SEQ ID NO:1. In some embodiments, X of formula (VI) comprises a sequence having at least 80% identity to SEQ ID NO:1. In some embodiments, X of formula (VI) comprises a sequence having at least 85% identity to SEQ ID NO:1. In some embodiments, X of formula (VI) comprises a sequence having at least 90% identity to SEQ ID NO:1. In some embodiments, X of formula (VI) comprises a sequence having at least 95% identity to SEQ ID NO:1. In some embodiments, X of formula (VI) comprises a sequence having at most 95% identity to SEQ ID NO:1. In some embodiments, X of formula (VI) comprises a sequence having at most 90% identity to SEQ ID NO:1. In some embodiments, X of formula (VI) comprises a sequence having at most 85% identity to SEQ ID NO:1. In some embodiments, X of formula (VI) comprises a sequence having at most 80% identity to SEQ ID NO:1. In some embodiments, X of formula (VI) comprises a sequence having at most 75% identity to SEQ ID NO:1.

[0165] In some embodiments, Y of formula (VI) is a moiety comprising a sequence having at least 70% identity to SEQ ID NO:2. In some embodiments, Y of formula (VI) is a moiety comprising a sequence having at least 75% identity to SEQ ID NO:2. In some embodiments, Y of formula (VI) is a moiety comprising a sequence having at least 80% identity to SEQ ID NO:2. In some embodiments, Y of formula (VI) is a moiety comprising a sequence having at least 85% identity to SEQ ID NO:2. In some embodiments, Y of formula (VI) is a moiety comprising a sequence having at least 90% identity to SEQ ID NO:2. In some embodiments, Y of formula (VI) is a moiety comprising a sequence having at least 95% identity to SEQ ID NO:2. In some embodiments, Y of formula (VI) is a sequence having at most 95% identity to SEQ ID NO:2. In some embodiments, Y of formula (VI) is a sequence having at most 90% identity to SEQ ID NO:2. In some embodiments, Y of formula (VI) is a sequence having at most 85% identity to SEQ ID NO:2. In some embodiments, Y of formula (VI) comprises a sequence having at most 80% identity to SEQ ID NO: 2. In some embodiments, Y of formula (VI) comprises a sequence having at most 75% identity to SEQ ID NO: 2.

[0166] In some embodiments, Y in formula (VI) is a hydrophobic moiety, 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 (VI) is a hydrophobic moiety, 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 (VI) is a hydrophobic moiety, 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 of formula (VI) is a hydrophobic moiety and at least 75% of the amino acids of Y are selected from I, V, L, F, C, M, and A. In some embodiments, Y of formula (VI) is a hydrophobic moiety and at least 80% of the amino acids of Y are selected from I, V, L, F, C, M, and A. In some embodiments, Y of formula (VI) is a hydrophobic moiety and at least 85% of the amino acids of Y are selected from I, V, L, F, C, M, and A. In some embodiments, Y of formula (VI) is a hydrophobic moiety and at least 90% of the amino acids of Y are selected from I, V, L, F, C, M, and A.

[0167] In some embodiments, X in formula (VI) is a moiety containing 40-65 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 in formula (VI) is a moiety containing 40-65 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 in formula (VI) is a moiety containing 40-65 amino acids, and the total number of W, Y, F, M, L, I, and V in X is 20 or less. In some embodiments, X in formula (VI) is a moiety containing 40-65 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.

[0168] In some embodiments, Y in formula (VI) is a moiety comprising 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 in formula (VI) is a moiety comprising 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 in formula (VI) is a moiety comprising 10 to 50 amino acids, and the total number of W, Y, F, M, L, I, and V in X is 20 or less. In some embodiments, Y in formula (VI) is a moiety 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.

[0169] In some embodiments, X in formula (VI) comprises a sequence having at least 70% identity to any one selected from SEQ ID NOs: 80-83. In some embodiments, X in formula (VI) comprises a sequence having at least 75% identity to any one selected from SEQ ID NOs: 80-83. In some embodiments, X in formula (VI) comprises a sequence having at least 80% identity to any one selected from SEQ ID NOs: 80-83. In some embodiments, X in formula (VI) comprises a sequence having at least 85% identity to any one selected from SEQ ID NOs: 80-83. In some embodiments, X in formula (VI) comprises a sequence having at least 90% identity to any one selected from SEQ ID NOs: 80-83. In some embodiments, X in formula (VI) comprises a sequence having at least 95% identity to any one selected from SEQ ID NOs: 80-83. In some embodiments, X of formula (VI) comprises a sequence having 96%, at least 97%, at least 98%, or at least 99% identity to any one selected from SEQ ID NOs: 80 to 83. In some embodiments, X of formula (VI) comprises any one sequence selected from SEQ ID NOs: 80 to 83. In some embodiments, X of formula (VI) is any one sequence selected from SEQ ID NOs: 80 to 83.

[0170] In some embodiments, Y of Formula (VI) comprises a sequence having at least 70% identity to SEQ ID NO:3. In some embodiments, Y of Formula (VI) comprises a sequence having at least 75% identity to SEQ ID NO:3. In some embodiments, Y of Formula (VI) comprises a sequence having at least 80% identity to SEQ ID NO:3. In some embodiments, Y of Formula (VI) comprises a sequence having at least 85% identity to SEQ ID NO:3. In some embodiments, Y of Formula (VI) comprises a sequence having at least 90% identity to SEQ ID NO:3. In some embodiments, Y of Formula (VI) comprises a sequence having at least 95% identity to 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 to 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.

[0171] In some embodiments, an artificial polypeptide of Formula (VI) comprises a sequence at least 70% identical to any one of SEQ ID NOs:90-93. In some embodiments, an artificial polypeptide of Formula (VI) comprises a sequence at least 75% identical to any one of SEQ ID NOs:90-93. In some embodiments, an artificial polypeptide of Formula (VI) comprises a sequence at least 80% identical to any one of SEQ ID NOs:90-93. In some embodiments, an artificial polypeptide of Formula (VI) comprises a sequence at least 85% identical to any one of SEQ ID NOs:90-93. In some embodiments, an artificial polypeptide of Formula (VI) comprises a sequence at least 90% identical to any one of SEQ ID NOs:90-93. In some embodiments, an artificial polypeptide of Formula (VI) comprises a sequence at least 95% identical to any one of SEQ ID NOs:90-93. In some embodiments, the artificial polypeptide of Formula (VI) comprises a sequence having 96%, at least 97%, at least 98%, or at least 99% identity to any one selected from SEQ ID NOs: 90-93. In some embodiments, the artificial polypeptide of Formula (VI) comprises a sequence selected from SEQ ID NOs: 90-93. In some embodiments, the artificial polypeptide of Formula (VI) is a sequence selected from SEQ ID NOs: 90-93.

[0172] In one embodiment, a method is provided for treating or preventing allergic conjunctivitis in a subject in need thereof, comprising administering an effective amount of an artificial polypeptide of formula (VII): XY(VII) administering to a subject: X is a portion of SEQ ID NO: 1 that comprises a variant, characterized in that the variant has at least 1, 2, 3, 4, or 5 amino acid insertions compared to SEQ ID NO: 1; Y is a moiety containing 10 to 30 amino acids, and Y includes a sequence having at least 15 consecutive AA of SEQ ID NO:2.

[0173] In some embodiments, X is a portion comprising a variant of SEQ ID NO:1, wherein the variant has at least 1, 2, 3, 4, or 5 amino acid insertions compared to SEQ ID NO:1. In some embodiments, X is a portion comprising a variant of SEQ ID NO:1, wherein the variant has at least one amino acid insertion compared to SEQ ID NO:1. In some embodiments, X is a portion comprising a variant of SEQ ID NO:1, wherein the variant has one amino acid insertion compared to SEQ ID NO:1. In some embodiments, X is a portion comprising a variant of SEQ ID NO:1, wherein the variant has at least two amino acid insertions compared to SEQ ID NO:1. In some embodiments, X is a portion comprising a variant of SEQ ID NO:1, wherein the variant has two amino acid insertions compared to SEQ ID NO:1. In some embodiments, X is a portion comprising a variant of SEQ ID NO:1, wherein the variant has at least three amino acid insertions compared to SEQ ID NO:1. In some embodiments, X is a portion comprising a variant of SEQ ID NO:1, wherein the variant has three amino acid insertions compared to SEQ ID NO:1. In some embodiments, X is a portion comprising a variant of SEQ ID NO:1, wherein the variant has at least four amino acid insertions compared to SEQ ID NO:1. In some embodiments, X is a portion comprising a variant of SEQ ID NO:1, wherein the variant has four amino acid insertions compared to SEQ ID NO:1. In some embodiments, X is a portion comprising a variant of SEQ ID NO: 1, wherein the variant is characterized by having at least a 5 amino acid insertion compared to SEQ ID NO: 1. In some embodiments, X is a portion comprising a variant of SEQ ID NO: 1, wherein the variant is characterized by having a 5 amino acid insertion compared to SEQ ID NO: 1.

[0174] In some embodiments, at least 20% of the amino acids of X in the variant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 25% of the amino acids of X in the variant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 30% of the amino acids of X in the variant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 35% of the amino acids of X in the variant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 40% of the amino acids of X in the variant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 45% of the amino acids of X in the variant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 50% of the amino acids of X in the variant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 55% of the amino acids of X in the variant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 60% of the amino acids of X in the variant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 65% of the amino acids of X in the variant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 70% of the amino acids of X in the variant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 75% of the amino acids of X in the variant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 80% of the amino acids of X in the variant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 85% of the amino acids of X in the variant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 90% of the amino acids of X in the variant are selected from R, K, N, D, Q, E, and H.

[0175] In some embodiments, Y is a moiety comprising 10-30 amino acids. In some embodiments, Y is a moiety comprising 10 amino acids, 11 amino acids, 12 amino acids, 13 amino acids, 14 amino acids, 15 amino acids, 16 amino acids, 17 amino acids, 18 amino acids, 19 amino acids, 20 amino acids, 21 amino acids, 22 amino acids, 23 amino acids, 24 amino acids, 25 amino acids, 26 amino acids, 27 amino acids, 28 amino acids, 29 amino acids, or 30 amino acids. In some embodiments, Y is a moiety comprising 11-29 amino acids. In some embodiments, Y is a moiety comprising 12-28 amino acids. In some embodiments, Y is a moiety comprising 13-27 amino acids. In some embodiments, Y is a moiety comprising 14-26 amino acids. In some embodiments, Y is a moiety comprising 15-25 amino acids. In some embodiments, Y is a moiety comprising 15-25 amino acids. In some embodiments, Y is a moiety comprising 18-25 amino acids. In some embodiments, Y is a moiety comprising 20-25 amino acids.

[0176] In some embodiments, Y comprises a sequence having at least 15 consecutive AAs of SEQ ID NO:2. In some embodiments, Y comprises a sequence having 15 consecutive AAs of SEQ ID NO:2. In some embodiments, Y comprises a sequence having at least 16 consecutive AAs of SEQ ID NO:2. In some embodiments, Y comprises a sequence having 16 consecutive AAs of SEQ ID NO:2. In some embodiments, Y comprises a sequence having at least 17 consecutive AAs of SEQ ID NO:2. In some embodiments, Y comprises a sequence having 17 consecutive AAs of SEQ ID NO:2. In some embodiments, Y comprises a sequence having at least 18 consecutive AAs of SEQ ID NO:2. In some embodiments, Y comprises a sequence having at least 18 consecutive AAs of SEQ ID NO:2. In some embodiments, Y comprises a sequence having at least 19 consecutive AAs of SEQ ID NO:2. In some embodiments, Y comprises a sequence having 19 consecutive AAs of SEQ ID NO:2. In some embodiments, Y comprises a sequence having at least 20 consecutive AAs of SEQ ID NO:2. In some embodiments, Y comprises a sequence having 20 consecutive AAs of SEQ ID NO:2. In some embodiments, Y comprises a sequence having at least 21 consecutive AA of SEQ ID NO:2. In some embodiments, Y comprises a sequence having 21 consecutive AA of SEQ ID NO:2. In some embodiments, Y comprises a sequence having at least 22 consecutive AA of SEQ ID NO:2. In some embodiments, Y comprises a sequence having at least 22 consecutive AA of SEQ ID NO:2. In some embodiments, Y comprises a sequence having at least 23 consecutive AA of SEQ ID NO:2. In some embodiments, Y comprises a sequence having 23 consecutive AA of SEQ ID NO:2. In some embodiments, Y comprises a sequence having at least 24 consecutive AA of SEQ ID NO:2. In some embodiments, Y comprises a sequence having 24 consecutive AA of SEQ ID NO:2. In some embodiments, Y comprises a sequence having at least 25 consecutive AA of SEQ ID NO:2. In some embodiments, Y comprises a sequence having 25 consecutive AA of SEQ ID NO:2.

[0177] In some embodiments, Y, is a moiety comprising a variant of SEQ ID NO:2, wherein the variant is characterized by 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 acids truncated relative to SEQ ID NO:2. In some embodiments, 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 acids truncated relative to SEQ ID NO:2. In some embodiments, 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 acids truncated relative to SEQ ID NO:2. In some embodiments, the 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20 amino acid truncation is located at the C-terminus of the Y.

[0178] 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 embodiments, 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 at most 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.

[0179] In some embodiments, X of formula (VII) is a moiety containing 40-65 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 moiety containing 40-65 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 moiety containing 40-65 amino acids, and the total number of W, Y, F, M, L, I, and V in X is 20 or less. In some embodiments, X of formula (VII) is a moiety containing 40-65 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.

[0180] In some embodiments, 40-65% of the amino acids of Y are selected from I, V, L, F, C, M, and A. In some embodiments, at least 40% of the amino acids of Y are selected from I, V, L, F, C, M, and A. In some embodiments, at least 45% of the amino acids of Y are selected from I, V, L, F, C, M, and A. In some embodiments, at least 50% of the amino acids of Y are selected from I, V, L, F, C, M, and A. In some embodiments, at least 55% of the amino acids of Y are selected from I, V, L, F, C, M, and A. In some embodiments, at least 60% of the amino acids of Y are selected from I, V, L, F, C, M, and A. In some embodiments, at most 65% of the amino acids of Y are selected from I, V, L, F, C, M, and A. In some embodiments, at most 60% of the amino acids of Y are selected from I, V, L, F, C, M, and A. In some embodiments, at most 55% of the amino acids of Y are selected from I, V, L, F, C, M, and A. In some embodiments, at most 50% of the amino acids of Y are selected from I, V, L, F, C, M, and A. In some embodiments, at most 45% of the amino acids of Y are selected from I, V, L, F, C, M, and A.

[0181] In some embodiments, the total number of R, K, T, A, N, Q, D, E, S, and G in Y is 10 or less. 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 15 or less. 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.

[0182] In some embodiments, X of Formula (VII) comprises a sequence having at least 70% identity to SEQ ID NO: 96. In some embodiments, X of Formula (VII) comprises a sequence having at least 75% identity to SEQ ID NO: 96. In some embodiments, X of Formula (VII) comprises a sequence having at least 80% identity to SEQ ID NO: 96. In some embodiments, X of Formula (VII) comprises a sequence having at least 85% identity to SEQ ID NO: 96. In some embodiments, X of Formula (VII) comprises a sequence having at least 90% identity to SEQ ID NO: 96. In some embodiments, X of Formula (VII) comprises a sequence having at least 95% identity to 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 to SEQ ID NO: 96. In some embodiments, X of Formula (VII) comprises the sequence of SEQ ID NO: 96. In some embodiments, X of Formula (VII) is the sequence of SEQ ID NO: 96.

[0183] In some embodiments, Y of formula (VII) comprises a sequence having at least 70% identity to any one selected from SEQ ID NOs: 97-103. In some embodiments, Y of formula (VII) comprises a sequence having at least 75% identity to any one selected from SEQ ID NOs: 97-103. In some embodiments, Y of formula (VII) comprises a sequence having at least 80% identity to any one selected from SEQ ID NOs: 97-103. In some embodiments, Y of formula (VII) comprises a sequence having at least 85% identity to any one selected from SEQ ID NOs: 97-103. In some embodiments, Y of formula (VII) comprises a sequence having at least 90% identity to any one selected from SEQ ID NOs: 97-103. In some embodiments, Y of formula (VII) comprises a sequence having at least 95% identity to any one selected from SEQ ID NOs: 97-103. In some embodiments, Y of formula (VII) comprises a sequence having 96%, at least 97%, at least 98%, or at least 99% identity to any one selected from SEQ ID NOs: 97 to 103. In some embodiments, Y of formula (VII) comprises a sequence that is any one selected from SEQ ID NOs: 97 to 103. In some embodiments, Y of formula (VII) is a sequence that is any one selected from SEQ ID NOs: 97 to 103.

[0184] In some embodiments, an artificial polypeptide of Formula (VII) comprises a sequence at least 70% identical to any one of SEQ ID NOs: 104-110. In some embodiments, an artificial polypeptide of Formula (VII) comprises a sequence at least 75% identical to any one of SEQ ID NOs: 104-110. In some embodiments, an artificial polypeptide of Formula (VII) comprises a sequence at least 80% identical to any one of SEQ ID NOs: 104-110. In some embodiments, an artificial polypeptide of Formula (VII) comprises a sequence at least 85% identical to any one of SEQ ID NOs: 104-110. In some embodiments, an artificial polypeptide of Formula (VII) comprises a sequence at least 90% identical to any one of SEQ ID NOs: 104-110. In some embodiments, an artificial polypeptide of Formula (VII) comprises a sequence at least 95% identical to any one of SEQ ID NOs: 104-110. In some embodiments, the artificial polypeptide of Formula (VII) comprises a sequence having 96%, at least 97%, at least 98%, or at least 99% identity to any one selected from SEQ ID NOs: 104-110. In some embodiments, the artificial polypeptide of Formula (VII) comprises a sequence selected from SEQ ID NOs: 104-110. In some embodiments, the artificial polypeptide of Formula (VII) is a sequence selected from SEQ ID NOs: 104-110.

[0185] In another aspect, a method for treating or preventing allergic conjunctivitis in a subject in need thereof is provided, comprising administering an effective amount of an artificial polypeptide variant of Formula (I). XY(I) administering to a subject: X is a portion containing a sequence having at least 80% identity with 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 contains a total number of cysteines (C) of less than 5, The mutant is characterized in that at least 1, 2, 3, 4, 5, 6, 7, 8, or 9 Ds in X are mutated to S, and / or at least 1, 2, 3, 4, 5, or 6 Es are mutated to T.

[0186] In some embodiments, at least 20% of the amino acids of X in the variant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 25% of the amino acids of X in the variant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 30% of the amino acids of X in the variant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 35% of the amino acids of X in the variant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 40% of the amino acids of X in the variant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 45% of the amino acids of X in the variant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 50% of the amino acids of X in the variant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 55% of the amino acids of X in the variant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 60% of the amino acids of X in the variant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 65% of the amino acids of X in the variant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 70% of the amino acids of X in the variant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 75% of the amino acids of X in the variant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 80% of the amino acids of X in the variant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 85% of the amino acids of X in the variant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 90% of the amino acids of X in the variant are selected from R, K, N, D, Q, E, and H.

[0187] In some embodiments, X in the variant comprises a sequence having at least 70% identity to SEQ ID NO:1. In some embodiments, X in the variant comprises a sequence having at least 75% identity to SEQ ID NO:1. In some embodiments, X in the variant comprises a sequence having at least 80% identity to SEQ ID NO:1. In some embodiments, X in the variant comprises a sequence having at least 85% identity to SEQ ID NO:1. In some embodiments, X in the variant comprises a sequence having at least 90% identity to SEQ ID NO:1. In some embodiments, X in the variant comprises a sequence having at least 95% identity to SEQ ID NO:1.

[0188] In some embodiments, Y in the variant may be a moiety comprising 10 to 50 amino acids, and the total number of cysteines (C) in Y is 5. In some embodiments, Y in the variant may be a moiety comprising 10 to 50 amino acids, and the total number of cysteines (C) in Y is less than 5. In some embodiments, Y in the variant may be a moiety comprising 10 to 50 amino acids, and the total number of cysteines (C) in Y is 4. In some embodiments, Y in the variant may be a moiety comprising 10 to 50 amino acids, and the total number of cysteines (C) in Y is less than 4. In some embodiments, Y in the variant may be a moiety comprising 10 to 50 amino acids, and the total number of cysteines (C) in Y is 3. In some embodiments, Y in the variant may be a moiety comprising 10 to 50 amino acids, and the total number of cysteines (C) in Y is less than 3. In some embodiments, Y in the variant may be a moiety comprising 10 to 50 amino acids, and the total number of cysteines (C) in Y is 2. In some embodiments, Y in the variant can be a moiety comprising 10-50 amino acids, and the total number of cysteines (C) in Y is less than 2. In some embodiments, Y in the variant can be a moiety comprising 10-50 amino acids, and the total number of cysteines (C) in Y is 1. In some embodiments, Y in the variant can be a moiety comprising 10-50 amino acids, and the total number of cysteines (C) in Y is less than 1. In some embodiments, Y in the variant can be a moiety comprising 10-50 amino acids, and the total number of cysteines (C) in Y is 0.

[0189] In some embodiments, the total number of hydrophobic amino acids in Y, in the variant is greater than 8. In some embodiments, the total number of hydrophobic amino acids in Y, in the variant is greater than 9. In some embodiments, the total number of hydrophobic amino acids in Y, in the variant is greater than 10. In some embodiments, the total number of hydrophobic amino acids in Y, in the variant is greater than 11. In some embodiments, the total number of hydrophobic amino acids in Y, in the variant is greater than 12. In some embodiments, the total number of hydrophobic amino acids in Y, in the variant is greater than 13. In some embodiments, the total number of hydrophobic amino acids in Y, in the variant is greater than 14. In some embodiments, the total number of hydrophobic amino acids in Y, in the variant is greater than 15.

[0190] In some embodiments, the total number of hydrophilic amino acids in Y, in the variant is 5. In some embodiments, the total number of hydrophilic amino acids in Y, in the variant is 5 or less. In some embodiments, the total number of hydrophilic amino acids in Y, in the variant is 4. In some embodiments, the total number of hydrophilic amino acids in Y, in the variant is 4 or less. In some embodiments, the total number of hydrophilic amino acids in Y, in the variant is 3. In some embodiments, the total number of hydrophilic amino acids in Y, in the variant is 3 or less. In some embodiments, the total number of hydrophilic amino acids in Y, in the variant is 2. In some embodiments, the total number of hydrophilic amino acids in Y, in the variant is 2 or less. In some embodiments, the total number of hydrophilic amino acids in Y, in the variant is 1. In some embodiments, the total number of hydrophilic amino acids in Y, in the variant is 1 or less.

[0191] In some embodiments, Y in the variant comprises a sequence having at least 70% identity to any one selected from SEQ ID NOs: 3-15, 58-61, and 84-85. In some embodiments, Y in the variant comprises a sequence having at least 75% identity to any one selected from SEQ ID NOs: 3-15, 58-61, and 84-85. In some embodiments, Y in the variant comprises a sequence having at least 80% identity to any one selected from SEQ ID NOs: 3-15, 58-61, and 84-85. In some embodiments, Y in the variant comprises a sequence having at least 85% identity to any one selected from SEQ ID NOs: 3-15, 58-61, and 84-85. In some embodiments, Y in the variant comprises a sequence having at least 90% identity to any one selected from SEQ ID NOs: 3-15, 58-61, and 84-85. In some embodiments, Y in the variant comprises a sequence having at least 95% identity to any one selected from SEQ ID NOs: 3-15, 58-61 and 84-85. In some embodiments, Y in the variant comprises a sequence having 96%, at least 97%, at least 98%, or at least 99% identity to any one selected from SEQ ID NOs: 3-15, 58-61 and 84-85. In some embodiments, Y in the variant comprises any one sequence selected from SEQ ID NOs: 3-15, 58-61 and 84-85. In some embodiments, Y in the variant is any one sequence selected from SEQ ID NOs: 3-15, 58-61 and 84-85.

[0192] In some embodiments, Y in the variant comprises a sequence having at least 70% identity to any one selected from SEQ ID NOs: 3-18, 58-61, and 84-85. In some embodiments, Y in the variant comprises a sequence having at least 75% identity to any one selected from SEQ ID NOs: 3-18, 58-61, and 84-85. In some embodiments, Y in the variant comprises a sequence having at least 80% identity to any one selected from SEQ ID NOs: 3-18, 58-61, and 84-85. In some embodiments, Y in the variant comprises a sequence having at least 85% identity to any one selected from SEQ ID NOs: 3-18, 58-61, and 84-85. In some embodiments, Y in the variant comprises a sequence having at least 90% identity to any one selected from SEQ ID NOs: 3-18, 58-61, and 84-85. In some embodiments, Y in the variant comprises a sequence having at least 95% identity to any one selected from SEQ ID NOs: 3-18, 58-61 and 84-85. In some embodiments, Y in the variant comprises a sequence having 96%, at least 97%, at least 98%, or at least 99% identity to any one selected from SEQ ID NOs: 3-18, 58-61 and 84-85. In some embodiments, Y in the variant comprises any one sequence selected from SEQ ID NOs: 3-18, 58-61 and 84-85. In some embodiments, Y in the variant is any one sequence selected from SEQ ID NOs: 3-18, 58-61 and 84-85.

[0193] In another aspect, a method is provided for treating or preventing allergic conjunctivitis in a subject in need thereof, comprising administering an effective amount of an artificial polypeptide variant of formula (II) XY(II) administering to a subject: X is a portion containing a sequence having at least 80% identity with 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 having at most 90% identity to SEQ ID NO:2, The mutant is characterized in that at least 1, 2, 3, 4, 5, 6, 7, 8, or 9 Ds in X are mutated to S, and / or at least 1, 2, 3, 4, 5, or 6 Es in X are mutated to T.

[0194] In some embodiments, at least 20% of the amino acids of X in the variant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 25% of the amino acids of X in the variant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 30% of the amino acids of X in the variant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 35% of the amino acids of X in the variant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 40% of the amino acids of X in the variant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 45% of the amino acids of X in the variant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 50% of the amino acids of X in the variant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 55% of the amino acids of X in the variant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 60% of the amino acids of X in the variant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 65% of the amino acids of X in the variant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 70% of the amino acids of X in the variant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 75% of the amino acids of X in the variant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 80% of the amino acids of X in the variant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 85% of the amino acids of X in the variant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 90% of the amino acids of X in the variant are selected from R, K, N, D, Q, E, and H.

[0195] In some embodiments, X in the variant comprises a sequence having at least 70% identity to SEQ ID NO:1. In some embodiments, X in the variant comprises a sequence having at least 75% identity to SEQ ID NO:1. In some embodiments, X in the variant comprises a sequence having at least 80% identity to SEQ ID NO:1. In some embodiments, X in the variant comprises a sequence having at least 85% identity to SEQ ID NO:1. In some embodiments, X in the variant comprises a sequence having at least 90% identity to SEQ ID NO:1. In some embodiments, X in the variant comprises a sequence having at least 95% identity to SEQ ID NO:1.

[0196] In some embodiments, Y in the variant comprises a sequence that has at most 50% identity to SEQ ID NO:2. In some embodiments, Y in the variant comprises a sequence that has at most 55% identity to SEQ ID NO:2. In some embodiments, Y in the variant comprises a sequence that has at most 60% identity to SEQ ID NO:2. In some embodiments, Y in the variant comprises a sequence that has at most 65% identity to SEQ ID NO:2. In some embodiments, Y in the variant comprises a sequence that has at most 70% identity to SEQ ID NO:2. In some embodiments, Y in the variant comprises a sequence that has at most 75% identity to SEQ ID NO:2. In some embodiments, Y in the variant comprises a sequence that has at most 80% identity to SEQ ID NO:2. In some embodiments, Y in the variant comprises a sequence that has at most 85% identity to SEQ ID NO:2. In some embodiments, Y in the variant comprises a sequence that has at most 90% identity to SEQ ID NO:2.

[0197] In some embodiments, the total number of hydrophobic amino acids in Y, in the variant is greater than 8. In some embodiments, the total number of hydrophobic amino acids in Y, in the variant is greater than 9. In some embodiments, the total number of hydrophobic amino acids in Y, in the variant is greater than 10. In some embodiments, the total number of hydrophobic amino acids in Y, in the variant is greater than 11. In some embodiments, the total number of hydrophobic amino acids in Y, in the variant is greater than 12. In some embodiments, the total number of hydrophobic amino acids in Y, in the variant is greater than 13. In some embodiments, the total number of hydrophobic amino acids in Y, in the variant is greater than 14. In some embodiments, the total number of hydrophobic amino acids in Y, in the variant is greater than 15.

[0198] In some embodiments, the total number of hydrophilic amino acids in Y, in the variant is 5. In some embodiments, the total number of hydrophilic amino acids in Y, in the variant is 5 or less. In some embodiments, the total number of hydrophilic amino acids in Y, in the variant is 4. In some embodiments, the total number of hydrophilic amino acids in Y, in the variant is 4 or less. In some embodiments, the total number of hydrophilic amino acids in Y, in the variant is 3. In some embodiments, the total number of hydrophilic amino acids in Y, in the variant is 3 or less. In some embodiments, the total number of hydrophilic amino acids in Y, in the variant is 2. In some embodiments, the total number of hydrophilic amino acids in Y, in the variant is 2 or less. In some embodiments, the total number of hydrophilic amino acids in Y, in the variant is 1. In some embodiments, the total number of hydrophilic amino acids in Y, in the variant is 1 or less.

[0199] In some embodiments, Y in the variant comprises a sequence having at least 70% identity to any one of SEQ ID NOs: 16-18. In some embodiments, Y in the variant comprises a sequence having at least 75% identity to any one of SEQ ID NOs: 16-18. In some embodiments, Y in the variant comprises a sequence having at least 80% identity to any one of SEQ ID NOs: 16-18. In some embodiments, Y in the variant comprises a sequence having at least 85% identity to any one of SEQ ID NOs: 16-18. In some embodiments, Y in the variant comprises a sequence having at least 90% identity to any one of SEQ ID NOs: 16-18. In some embodiments, Y in the variant comprises a sequence having at least 95% identity to any one of SEQ ID NOs: 16-18. In some embodiments, Y in the variant comprises a sequence having 96%, at least 97%, at least 98%, or at least 99% identity to any one of SEQ ID NOs: 16-18. In some embodiments, Y in the variant comprises any one of the sequences selected from SEQ ID NOs: 16 to 18. In some embodiments, Y in the variant is any one of the sequences selected from SEQ ID NOs: 16 to 18.

[0200] In another aspect, a method is provided for treating or preventing allergic conjunctivitis in a subject in need thereof, comprising administering an effective amount of an artificial polypeptide variant of formula (III) XY(III) administering to a subject: 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 portion containing 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; The mutant is characterized in that at least 1, 2, 3, 4, 5, 6, 7, 8, or 9 Ds in X are mutated to S, and / or at least 1, 2, 3, 4, 5, or 6 Es in X are mutated to T.

[0201] In some embodiments, at least 20% of the amino acids of X in the variant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 25% of the amino acids of X in the variant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 30% of the amino acids of X in the variant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 35% of the amino acids of X in the variant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 40% of the amino acids of X in the variant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 45% of the amino acids of X in the variant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 50% of the amino acids of X in the variant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 55% of the amino acids of X in the variant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 60% of the amino acids of X in the variant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 65% of the amino acids of X in the variant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 70% of the amino acids of X in the variant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 75% of the amino acids of X in the variant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 80% of the amino acids of X in the variant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 85% of the amino acids of X in the variant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 90% of the amino acids of X in the variant are selected from R, K, N, D, Q, E, and H.

[0202] In some embodiments, X in the variant is a moiety comprising 40-65 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 in the variant is a moiety comprising 40-65 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 variant is a moiety comprising 40-65 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 variant is a moiety comprising 40-65 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 variant is a moiety comprising 40-65 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 variant is a moiety comprising 40-65 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 variant is a moiety comprising 40-65 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 variant is a moiety comprising 40-65 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 variant is a moiety comprising 40-65 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 variant is a moiety comprising 40-65 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 variant is a moiety comprising 40-65 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 variant is a moiety comprising 40-65 amino acids, and the total number of H, R, K, D, Q, N, and E in X is less than 22. In some embodiments, X in the variant is a moiety comprising 40-65 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 variant is a moiety comprising 40-65 amino acids, and the total number of H, R, K, D, Q, N, and E in X is less than 20.

[0203] In some embodiments, X in the variant is a moiety containing 40-65 amino acids, and the total number of hydrophilic amino acids in X is greater than 10. In some embodiments, X in the variant is a moiety containing 40-65 amino acids, and the total number of hydrophilic amino acids in X is greater than 11. In some embodiments, X in the variant is a moiety containing 40-65 amino acids, and the total number of hydrophilic amino acids in X is greater than 12. In some embodiments, X in the variant is a moiety containing 40-65 amino acids, and the total number of hydrophilic amino acids in X is greater than 13. In some embodiments, X in the variant is a moiety containing 40-65 amino acids, and the total number of hydrophilic amino acids in X is greater than 14. In some embodiments, X in the variant is a moiety containing 40-65 amino acids, and the total number of hydrophilic amino acids in X is greater than 15. In some embodiments, X in the variant is a moiety containing 40-65 amino acids, and the total number of hydrophilic amino acids in X is greater than 16. In some embodiments, X in the variant is a moiety containing 40-65 amino acids, and the total number of hydrophilic amino acids in X is greater than 17. In some embodiments, X in the variant is a moiety containing 40-65 amino acids, and the total number of hydrophilic amino acids in X is greater than 18. In some embodiments, X in the variant is a moiety containing 40-65 amino acids, and the total number of hydrophilic amino acids in X is greater than 19. In some embodiments, X in the variant is a moiety containing 40-65 amino acids, and the total number of hydrophilic amino acids in X is greater than 20. In some embodiments, X in the variant is a moiety containing 40-65 amino acids, and the total number of hydrophilic amino acids in X is greater than 21. In some embodiments, X in the variant is a moiety containing 40-65 amino acids, and the total number of hydrophilic amino acids in X is greater than 22. In some embodiments, X in the variant is a moiety containing 40-65 amino acids, and the total number of hydrophilic amino acids in X is greater than 23. In some embodiments, X in the variant is a moiety comprising 40-65 amino acids, and the total number of hydrophilic amino acids in X is greater than 24. In some embodiments, X in the variant is a moiety comprising 40-65 amino acids, and the total number of hydrophilic amino acids in X is greater than 25.

[0204] In some embodiments, X in the variant is a moiety containing 40 to 65 amino acids, and the total number of hydrophobic amino acids in X is 15 or less. In some embodiments, X in the variant is a moiety containing 40 to 65 amino acids, and the total number of hydrophobic amino acids in X is 14 or less. In some embodiments, X in the variant is a moiety containing 40 to 65 amino acids, and the total number of hydrophobic amino acids in X is 13 or less. In some embodiments, X in the variant is a moiety containing 40 to 65 amino acids, and the total number of hydrophobic amino acids in X is 12 or less. In some embodiments, X in the variant is a moiety containing 40 to 65 amino acids, and the total number of hydrophobic amino acids in X is 11 or less. In some embodiments, X in the variant is a moiety containing 40 to 65 amino acids, and the total number of hydrophobic amino acids in X is 10 or less. In some embodiments, X in the variant is a moiety containing 40 to 65 amino acids, and the total number of hydrophobic amino acids in X is 5 or less.

[0205] In some embodiments, X in the variant comprises a sequence having at least 70% identity to SEQ ID NO:1. In some embodiments, X in the variant comprises a sequence having at least 75% identity to SEQ ID NO:1. In some embodiments, X in the variant comprises a sequence having at least 80% identity to SEQ ID NO:1. In some embodiments, X in the variant comprises a sequence having at least 85% identity to SEQ ID NO:1. In some embodiments, X in the variant comprises a sequence having at least 90% identity to SEQ ID NO:1. In some embodiments, X in the variant comprises a sequence having at least 95% identity to SEQ ID NO:1.

[0206] In some embodiments, Y in the variant is a moiety comprising a sequence having at least 70% identity to SEQ ID NO:2. In some embodiments, Y in the variant is a moiety comprising a sequence having at least 75% identity to SEQ ID NO:2. In some embodiments, Y in the variant is a moiety comprising a sequence having at least 80% identity to SEQ ID NO:2. In some embodiments, Y in the variant is a moiety comprising a sequence having at least 85% identity to SEQ ID NO:2. In some embodiments, Y in the variant is a moiety comprising a sequence having at least 90% identity to SEQ ID NO:2. In some embodiments, Y in the variant is a moiety comprising a sequence having at least 95% identity to SEQ ID NO:2. In some embodiments, Y in the variant is a moiety comprising a sequence having at least 96%, at least 97%, at least 98%, or at least 99% identity to SEQ ID NO:2. In some embodiments, Y in the variant is a moiety comprising the sequence of SEQ ID NO:2. In some embodiments, Y in the variant is a moiety which is the sequence of SEQ ID NO:2.

[0207] In some embodiments, Y in the variant is a hydrophobic moiety, and at least 50% of the amino acids of Y are selected from I, V, L, F, C, M, and A. In some embodiments, Y in the variant is a hydrophobic moiety, and at least 55% of the amino acids of Y are selected from I, V, L, F, C, M, and A. In some embodiments, Y in the variant is a hydrophobic moiety, and at least 60% of the amino acids of Y are selected from I, V, L, F, C, M, and A. In some embodiments, Y in the variant is a hydrophobic moiety, and at least 65% of the amino acids of Y are selected from I, V, L, F, C, M, and A. In some embodiments, Y in the variant is a hydrophobic moiety, and at least 70% of the amino acids of Y are selected from I, V, L, F, C, M, and A. In some embodiments, Y in the variant is a hydrophobic moiety, and at least 75% of the amino acids of Y are selected from I, V, L, F, C, M, and A. In some embodiments, Y in the variant is a hydrophobic moiety and at least 80% of the amino acids of Y are selected from I, V, L, F, C, M, and A. In some embodiments, Y in the variant is a hydrophobic moiety and at least 85% of the amino acids of Y are selected from I, V, L, F, C, M, and A. In some embodiments, Y in the variant is a hydrophobic moiety and at least 90% of the amino acids of Y are selected from I, V, L, F, C, M, and A.

[0208] In another aspect, a method is provided for treating or preventing allergic conjunctivitis in a subject in need thereof, comprising administering an effective amount of an artificial polypeptide variant of formula (IV). XY(IV) administering to a subject: 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 portion containing a sequence having at least 80% identity with SEQ ID NO: 2, X comprises a sequence having at most 90% identity to SEQ ID NO: 1; The mutant is characterized in that at least 1, 2, 3, 4, 5, 6, 7, 8, or 9 Ds in X are mutated to S, and / or at least 1, 2, 3, 4, 5, or 6 Es in X are mutated to T.

[0209] In some embodiments, at least 20% of the amino acids of X in the variant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 25% of the amino acids of X in the variant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 30% of the amino acids of X in the variant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 35% of the amino acids of X in the variant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 40% of the amino acids of X in the variant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 45% of the amino acids of X in the variant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 50% of the amino acids of X in the variant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 55% of the amino acids of X in the variant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 60% of the amino acids of X in the variant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 65% of the amino acids of X in the variant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 70% of the amino acids of X in the variant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 75% of the amino acids of X in the variant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 80% of the amino acids of X in the variant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 85% of the amino acids of X in the variant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 90% of the amino acids of X in the variant are selected from R, K, N, D, Q, E, and H.

[0210] In some embodiments, X in the variant comprises 40-65 amino acids, and the total number of hydrophilic amino acids in X is greater than 10. In some embodiments, X in the variant comprises 40-65 amino acids, and the total number of hydrophilic amino acids in X is greater than 15. In some embodiments, X in the variant comprises 40-65 amino acids, and the total number of hydrophilic amino acids in X is greater than 20. In some embodiments, X in the variant comprises 40-65 amino acids, and the total number of hydrophilic amino acids in X is greater than 25. In some embodiments, X in the variant comprises 40-65 amino acids, and the total number of hydrophilic amino acids in X is greater than 30. In some embodiments, X in the variant comprises 40-65 amino acids, and the total number of hydrophilic amino acids in X is greater than 35.

[0211] In some embodiments, X in the variant is a moiety containing 40 to 65 amino acids, and the total number of hydrophobic amino acids in X is 15 or less. In some embodiments, X in the variant is a moiety containing 40 to 65 amino acids, and the total number of hydrophobic amino acids in X is 14 or less. In some embodiments, X in the variant is a moiety containing 40 to 65 amino acids, and the total number of hydrophobic amino acids in X is 13 or less. In some embodiments, X in the variant is a moiety containing 40 to 65 amino acids, and the total number of hydrophobic amino acids in X is 12 or less. In some embodiments, X in the variant is a moiety containing 40 to 65 amino acids, and the total number of hydrophobic amino acids in X is 11 or less. In some embodiments, X in the variant is a moiety containing 40 to 65 amino acids, and the total number of hydrophobic amino acids in X is 10 or less. In some embodiments, X in the variant is a moiety containing 40 to 65 amino acids, and the total number of hydrophobic amino acids in X is 5 or less.

[0212] In some embodiments, X in the variant comprises a sequence having at least 70% identity to SEQ ID NO:1. In some embodiments, X in the variant comprises a sequence having at least 75% identity to SEQ ID NO:1. In some embodiments, X in the variant comprises a sequence having at least 80% identity to SEQ ID NO:1. In some embodiments, X in the variant comprises a sequence having at least 85% identity to SEQ ID NO:1. In some embodiments, X in the variant comprises a sequence having at least 90% identity to SEQ ID NO:1. In some embodiments, X in the variant comprises a sequence having at least 95% identity to SEQ ID NO:1.

[0213] In some embodiments, Y in the variant is a moiety comprising a sequence having at least 70% identity to SEQ ID NO:2. In some embodiments, Y in the variant is a moiety comprising a sequence having at least 75% identity to SEQ ID NO:2. In some embodiments, Y in the variant is a moiety comprising a sequence having at least 80% identity to SEQ ID NO:2. In some embodiments, Y in the variant is a moiety comprising a sequence having at least 85% identity to SEQ ID NO:2. In some embodiments, Y in the variant is a moiety comprising a sequence having at least 90% identity to SEQ ID NO:2. In some embodiments, Y in the variant is a moiety comprising a sequence having at least 95% identity to SEQ ID NO:2. In some embodiments, Y in the variant is a moiety comprising a sequence having at least 96%, at least 97%, at least 98%, or at least 99% identity to SEQ ID NO:2. In some embodiments, Y in the variant is a moiety comprising the sequence of SEQ ID NO:2. In some embodiments, Y in the variant is a moiety which is the sequence of SEQ ID NO:2.

[0214] In some embodiments, Y in the variant is a hydrophobic moiety, and at least 50% of the amino acids of Y are selected from I, V, L, F, C, M, and A. In some embodiments, Y in the variant is a hydrophobic moiety, and at least 55% of the amino acids of Y are selected from I, V, L, F, C, M, and A. In some embodiments, Y in the variant is a hydrophobic moiety, and at least 60% of the amino acids of Y are selected from I, V, L, F, C, M, and A. In some embodiments, Y in the variant is a hydrophobic moiety, and at least 65% of the amino acids of Y are selected from I, V, L, F, C, M, and A. In some embodiments, Y in the variant is a hydrophobic moiety, and at least 70% of the amino acids of Y are selected from I, V, L, F, C, M, and A. In some embodiments, Y in the variant is a hydrophobic moiety, and at least 75% of the amino acids of Y are selected from I, V, L, F, C, M, and A. In some embodiments, Y in the variant is a hydrophobic moiety and at least 80% of the amino acids of Y are selected from I, V, L, F, C, M, and A. In some embodiments, Y in the variant is a hydrophobic moiety and at least 85% of the amino acids of Y are selected from I, V, L, F, C, M, and A. In some embodiments, Y in the variant is a hydrophobic moiety and at least 90% of the amino acids of Y are selected from I, V, L, F, C, M, and A.

[0215] In another aspect, a method is provided for treating or preventing allergic conjunctivitis in a subject in need thereof, comprising administering an effective amount of an artificial polypeptide variant of formula (V): XY(V) administering to a subject: X is a portion containing a sequence having at least 80% identity with SEQ ID NO: 1; Y is a moiety containing 10 to 30 amino acids, and Y comprises a sequence having at least 10 consecutive AA of SEQ ID NO: 2; The mutant is characterized in that at least 1, 2, 3, 4, 5, 6, 7, 8, or 9 Ds in X are mutated to S, and / or at least 1, 2, 3, 4, 5, or 6 Es in X are mutated to T.

[0216] In some embodiments, at least 20% of the amino acids of X in the variant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 25% of the amino acids of X in the variant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 30% of the amino acids of X in the variant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 35% of the amino acids of X in the variant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 40% of the amino acids of X in the variant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 45% of the amino acids of X in the variant are selected from R, K, N, D, Q, E, and H. In some embodiments, at least 50% of the amino acids of X in the variant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 55% of the amino acids of X in the variant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 60% of the amino acids of X in the variant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 65% of the amino acids of X in the variant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 70% of the amino acids of X in the variant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 75% of the amino acids of X in the variant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 80% of the amino acids of X in the variant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 85% of the amino acids of X in the variant are selected from R, K, N, D, Q, E, and H. In some embodiments, at most 90% of the amino acids of X in the variant are selected from R, K, N, D, Q, E, and H.

[0217] In some embodiments, Y in the variant comprises 10-25 amino acids. In some embodiments, Y in the variant comprises 10-20 amino acids. In some embodiments, Y in the variant comprises 10-15 amino acids. In some embodiments, Y in the variant 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.

[0218] In some embodiments, X in the variant comprises a sequence having at least 70% identity to SEQ ID NO:1. In some embodiments, X in the variant comprises a sequence having at least 75% identity to SEQ ID NO:1. In some embodiments, X in the variant comprises a sequence having at least 80% identity to SEQ ID NO:1. In some embodiments, X in the variant comprises a sequence having at least 85% identity to SEQ ID NO:1. In some embodiments, X in the variant comprises a sequence having at least 90% identity to SEQ ID NO:1. In some embodiments, X in the variant comprises a sequence having at least 95% identity to SEQ ID NO:1.

[0219] In some embodiments, Y in the variant comprises a sequence that has at most 50% identity to SEQ ID NO:2. In some embodiments, Y in the variant comprises a sequence that has at most 55% identity to SEQ ID NO:2. In some embodiments, Y in the variant comprises a sequence that has at most 60% identity to SEQ ID NO:2. In some embodiments, Y in the variant comprises a sequence that has at most 65% identity to SEQ ID NO:2. In some embodiments, Y in the variant comprises a sequence that has at most 70% identity to SEQ ID NO:2. In some embodiments, Y in the variant comprises a sequence that has at most 75% identity to SEQ ID NO:2. In some embodiments, Y in the variant comprises a sequence that has at most 80% identity to SEQ ID NO:2. In some embodiments, Y in the variant comprises a sequence that has at most 85% identity to SEQ ID NO:2. In some embodiments, Y in the variant comprises a sequence that has at most 90% identity to SEQ ID NO:2.

[0220] In another aspect, a method for treating or preventing allergic conjunctivitis in a subject in need thereof is provided, comprising administering to the subject an effective amount of a polypeptide having at least 70% identity to any one selected from SEQ ID NO: 28, SEQ ID NOs: 57, and 62-74, or a fragment or variant thereof.

[0221] In some embodiments, the polypeptide has at least 70% identity to any one selected from SEQ ID NO:28, SEQ ID NO:57, and 62-74, or a fragment or variant thereof. In some embodiments, the polypeptide has at least 75% identity to any one selected from SEQ ID NO:28, SEQ ID NO:57, and 62-74, or a fragment or variant thereof. In some embodiments, the polypeptide has at least 80% identity to any one selected from SEQ ID NO:28, SEQ ID NO:57, and 62-74, or a fragment or variant thereof. In some embodiments, the polypeptide has at least 85% identity to any one selected from SEQ ID NO:28, SEQ ID NO:57, and 62-74, or a fragment or variant thereof. In some embodiments, the polypeptide has at least 90% identity to any one selected from SEQ ID NO:28, SEQ ID NO:57, and 62-74, or a fragment or variant thereof. In some embodiments, the polypeptide has at least 95% identity to any one selected from SEQ ID NO:28, SEQ ID NO:57, and 62-74, or a fragment or variant thereof. In some embodiments, the polypeptide has at least 96%, at least 97%, at least 98%, or at least 99% identity to any one selected from SEQ ID NO:28, SEQ ID NO:57, and 62-74, or a fragment or variant thereof. In some embodiments, the polypeptide comprises or is any one amino acid sequence selected from SEQ ID NO:28, SEQ ID NO:57, and 62-74, or a fragment or variant thereof. In some embodiments, the polypeptide is any one of SEQ ID NO:28, SEQ ID NO:57, and 62-74 ...62-74. In some embodiments, the polypeptide is the polypeptide of SEQ ID NO:28.

[0222] In another aspect, there is provided an artificial polypeptide of formula (I), (II), (III), (IV), (V), (VI), or (VII), or a variant of an artificial polypeptide of (I), (II), (III), (IV) or (V), or a polypeptide having at least 70% identity to any one selected from SEQ ID NO: 28, SEQ ID NOs: 57, and 62-74, or a fragment or variant thereof, for use in treating or preventing allergic conjunctivitis in a subject in need thereof.

[0223] In another aspect, there is provided use of an artificial polypeptide of formula (I), (II), (III), (IV), (V), (VI), or (VII), or a variant of an artificial polypeptide of (I), (II), (III), (IV) or (V), or a polypeptide having at least 70% identity to any one selected from SEQ ID NO: 28, SEQ ID NOs: 57, and 62-74, or a fragment or variant thereof, for the preparation of a medicament for treating or preventing allergic conjunctivitis in a subject in need thereof.

[0224] In some embodiments, the medicament is for use in humans.

[0225] In some embodiments, the medicament is a veterinary medicament.

[0226] In some embodiments of any of the above aspects, the subject is a mammal. In some embodiments, the subject is any one selected from the group consisting of a human, a primate, a rodent, a dog, a cat, a horse, a sheep, and a pig. In some embodiments, the subject is a human. In some embodiments, the subject is an infant, a toddler, a child, an adolescent, an adult, or an elderly person. In some embodiments, the subject is a male or a female. In some embodiments, the subject is a pet. In some embodiments, the subject is any one selected from the group consisting of a mouse, a rat, a guinea pig, a gerbil, a hamster, a chinchilla, a rabbit, a ferret, a cat, a dog, and a pig.

[0227] In some embodiments of any of the above aspects, 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 phlyctenular keratoconjunctivitis.

[0228] In some embodiments, the allergic conjunctivitis is seasonal allergic conjunctivitis. In some embodiments, the seasonal allergic conjunctivitis is caused or partially caused by seasonal allergens. In some embodiments, the seasonal allergic conjunctivitis is caused by seasonal allergens. In some embodiments, the seasonal allergic conjunctivitis is partially caused by seasonal allergens. In some embodiments, the seasonal allergen is at least one selected from the group consisting of tree pollen, weed pollen, grass pollen, and mold spores. In some embodiments, the seasonal allergen is selected from the group consisting of tree pollen. In some embodiments, the seasonal allergen is selected from the group consisting of weed pollen. In some embodiments, the seasonal allergen is selected from the group consisting of grass pollen. In some embodiments, the seasonal allergen is selected from the group consisting of mold spores. In some embodiments, the seasonal allergen is two, three, or four selected from the group consisting of tree pollen, weed pollen, grass pollen, and mold spores.

[0229] In some embodiments, the allergic conjunctivitis is perennial allergic conjunctivitis. In some embodiments, the perennial allergic conjunctivitis is caused or partially caused by a perennial allergen. In some embodiments, the perennial allergic conjunctivitis is caused by a perennial allergen. In some embodiments, the perennial allergic conjunctivitis is partially caused by a perennial allergen. In some embodiments, the perennial allergen is at least one selected from the group consisting of house dust mites, cockroaches, and animal dander. In some embodiments, the perennial allergen is selected from the group consisting of house dust mites. In some embodiments, the perennial allergen is selected from the group consisting of cockroaches. In some embodiments, the perennial allergen is selected from the group consisting of animal dander. In some embodiments, the animal is a companion animal, such as a cat, dog, rabbit, pig, ferret, hamster, gerbil, chinchilla, rat, mouse, guinea pig, and bird, such as a parrot. In some embodiments, the perennial allergens are two or three selected from the group consisting of house dust mites, cockroaches, and animal dander.

[0230] In some embodiments, the allergic conjunctivitis is vernal keratoconjunctivitis. In some embodiments, the vernal keratoconjunctivitis is at least one selected from the group consisting of palpebral vernal keratoconjunctivitis, limbal vernal keratoconjunctivitis, and mixed vernal keratoconjunctivitis. In some embodiments, the vernal keratoconjunctivitis is palpebral vernal keratoconjunctivitis. In some embodiments, the vernal keratoconjunctivitis is limbal vernal keratoconjunctivitis. In some embodiments, the vernal keratoconjunctivitis is mixed vernal keratoconjunctivitis.

[0231] In some embodiments, the allergic conjunctivitis is giant papillary conjunctivitis. In some embodiments, the giant papillary conjunctivitis is caused or partially caused by repeated mechanical irritation of the conjunctiva. In some embodiments, the giant papillary conjunctivitis is caused by repeated mechanical irritation of the conjunctiva. In some embodiments, the giant papillary conjunctivitis is partially caused by repeated mechanical irritation of the conjunctiva. In some embodiments, the repeated mechanical irritation 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 an extruding scleral buckle, and elevated corneal scars. In some embodiments, the repeated mechanical irritation of the conjunctiva is associated with contact lens wear. In some embodiments, the contact lens is at least one selected from the group consisting of a soft lens, a hard lens, a hydrogel lens, and a silicone hydrogel lens. In some embodiments, the repeated mechanical irritation of the conjunctiva is associated with use of an ocular prosthesis. In some embodiments, the repeated mechanical irritation of the conjunctiva is associated with use of a conjunctival suture. In some embodiments, the repeated mechanical stimulation of the conjunctiva is associated with a protruding scleral buckle. In some embodiments, the repeated mechanical stimulation of the conjunctiva is associated with a raised corneal scar. In some embodiments, the repeated mechanical stimulation of the conjunctiva is associated with two, three, four, or five selected from the group consisting of contact lens wear, use of an ocular prosthesis, use of conjunctival sutures, use of a protruding scleral buckle, and a raised corneal scar.

[0232] In some embodiments, the allergic conjunctivitis is atopic keratoconjunctivitis. In some embodiments, the atopic keratoconjunctivitis is associated with atopic dermatitis and / or asthma. In some embodiments, the atopic keratoconjunctivitis is associated with atopic dermatitis. In some embodiments, the atopic keratoconjunctivitis is associated with asthma. In some embodiments, the atopic keratoconjunctivitis is associated with atopic dermatitis and asthma.

[0233] In some embodiments, allergic conjunctivitis is phlyctenular keratoconjunctivitis.In some embodiments, phlyctenular keratoconjunctivitis is caused or partially caused by the delayed hypersensitivity or inflammatory reaction of the cornea and conjunctiva to the antigens expressed by various pathogens.In some embodiments, phlyctenular keratoconjunctivitis is caused or partially caused by the delayed hypersensitivity or inflammatory reaction of the cornea and conjunctiva to the antigens expressed by various pathogens.In some embodiments, phlyctenular keratoconjunctivitis is caused or partially caused by the delayed hypersensitivity or inflammatory reaction of the cornea and conjunctiva to the antigens expressed by various pathogens. In some embodiments, the pathogen is at least one selected from the group consisting of bacteria (e.g., Staphylococcus aureus, Streptococcus viridians, Mycobacterium tuberculosis), viruses (e.g., herpes simplex virus), chlamydia, fungi (e.g., Candida, e.g., Candida albicans), and parasites (e.g., tapeworms, e.g., Hymenolepis nana; and nematodes). In some embodiments, the pathogen is a bacterium. In some embodiments, the bacterium is Staphylococcus aureus. In some embodiments, the bacterium is Streptococcus viridians. In some embodiments, the bacterium is Mycobacterium tuberculosis. In some embodiments, the bacterium is at least one selected from the group consisting of Staphylococcus aureus, Streptococcus viridians, and Mycobacterium tuberculosis. In some embodiments, the pathogen is a virus. In some embodiments, the virus is herpes simplex virus. In some embodiments, the pathogen is Chlamydia. In some embodiments, the pathogen is a fungus. In some embodiments, the fungus is Candida. In some embodiments, the Candida is Candida albicans. In some embodiments, the pathogen is a parasite. In some embodiments, the parasite is an intestinal parasite. In some embodiments, the parasite is a tapeworm.In some embodiments, the tapeworm is Hymenolepis nana. In some embodiments, the parasite is a nematode. In some embodiments, the pathogen is selected from the group consisting of bacteria (e.g., Staphylococcus aureus, Streptococcus viridians, Mycobacterium tuberculosis), viruses (e.g., herpes simplex virus), chlamydia, fungi (e.g., Candida, e.g., Candida albicans), and parasites (e.g., tapeworms, e.g., Hymenolepis nana; and nematodes).

[0234] In some embodiments, the subject does not have any ocular disease selected from the group consisting of viral conjunctivitis, bacterial conjunctivitis, chemical conjunctivitis, and dry eye or a dry eye-related disorder. In some embodiments, the subject does not have viral conjunctivitis. In some embodiments, the subject does not have bacterial conjunctivitis. In some embodiments, the subject does not have chemical conjunctivitis. In some embodiments, the subject does not have dry eye (DE) or a dry eye (DE)-related disorder. In some embodiments, the dry eye (DE) or dry eye (DE) related disorder is dry eye syndrome, dysfunctional tear syndrome, keratoconjunctivitis sicca (KCS), lacrimal keratoconjunctivitis, aqueous tear-deficient DE, evaporative DE, Sjogren's syndrome DE, non-Sjogren's syndrome DE, conjunctivitis-related DE, post-viral conjunctivitis DE, post-cataract surgery DE, VDT operation-related DE, contact lens wear-related DE, environmental DE, corneal neovascularization DE, allergic DE, LASIK-induced neurotrophic epitheliopathy, aqueous tear deficiency (hypolacrimation), xerophthalmia, Stevens-Johnson syndrome, ocular cicatricial pemphigoid, ocular pemphigoid, blepharitis, eyelid closure failure), corneal ulcer, blepharitis and eye redness.

[0235] In some embodiments, the subject is a patient receiving an artificial polypeptide of Formula (I), (II), (III), (IV), (V), (VI), or (VII), or a variant of an artificial polypeptide of (I), (II), (III), (IV), or (V), or a polypeptide having at least 70% identity to any one selected from SEQ ID NO: 28, SEQ ID NOs: 57, and 62-74, or a fragment or variant thereof ("artificial polypeptide of Formula (I), (II), (III), (IV), (V), (VI), or (VII"). or a variant of the artificial polypeptide of (I), (II), (III), (IV), or (V), or a polypeptide having at least 70% identity to any one selected from SEQ ID NO: 28, SEQ ID NO: 57, and SEQ ID NO: 62-74, or a fragment or variant thereof (collectively referred to herein for brevity as the "polypeptides of the present disclosure"), the subject experiences at least one symptom selected from the group consisting of conjunctival redness, conjunctival edema, conjunctival congestion, eyelid redness, eyelid edema, eyelid congestion, itchy eyes, visible corneal damage, mucous discharge, watery discharge, tearing, photophobia, foreign body sensation, and difficulty opening the eyes. In some embodiments, the subject experiences conjunctival redness prior to administration of the polypeptide of the present disclosure. In some embodiments, the subject experiences conjunctival edema prior to administration of the polypeptide of the present disclosure. In some embodiments, the subject experiences conjunctival hyperemia prior to administration of a polypeptide of the present disclosure. In some embodiments, the subject experiences eyelid redness prior to administration of a polypeptide of the present disclosure. In some embodiments, the subject experiences eyelid edema prior to administration of a polypeptide of the present disclosure. In some embodiments, the subject experiences eyelid hyperemia prior to administration of a polypeptide of the present disclosure. In some embodiments, the subject experiences ocular itching prior to administration of a polypeptide of the present disclosure. In some embodiments, the subject experiences visible corneal damage prior to administration of a polypeptide of the present disclosure. In some embodiments, the subject experiences mucous ocular discharge prior to administration of a polypeptide of the present disclosure. In some embodiments, the subject experiences watery ocular discharge prior to administration of a polypeptide of the present disclosure. In some embodiments, the subject experiences tearing prior to administration of a polypeptide of the present disclosure.In some embodiments, the subject experiences photophobia before administration of the polypeptide of the present disclosure. In some embodiments, the subject experiences foreign body sensation before administration of the polypeptide of the present disclosure. In some embodiments, the subject experiences difficulty opening their eyes before administration of the polypeptide of the present disclosure. In some embodiments, the subject experiences 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 or 14 symptoms selected from the group consisting of conjunctival redness, conjunctival edema, conjunctival congestion, eyelid redness, eyelid edema, eyelid congestion, itchy eyes, visible corneal damage, mucous eye discharge, watery eye discharge, tearing, photophobia, foreign body sensation and difficulty opening their eyes.

[0236] In some embodiments, after administering at least one dose of a polypeptide of the present disclosure, the subject exhibits a reduction in at least one symptom selected from the group consisting of conjunctival redness, conjunctival edema, conjunctival congestion, eyelid redness, eyelid edema, eyelid congestion, itchy eyes, visible corneal damage, mucous discharge, watery discharge, tearing, photophobia, foreign body sensation, and difficulty opening the eyes. In some embodiments, after administering at least one dose of a polypeptide of the present disclosure, the subject exhibits a reduction in conjunctival redness. In some embodiments, after administering at least one dose of a polypeptide of the present disclosure, the subject exhibits a reduction in conjunctival edema. In some embodiments, after administering at least one dose of a polypeptide of the present disclosure, the subject exhibits a reduction in conjunctival congestion. In some embodiments, after administering at least one dose of a polypeptide of the present disclosure, the subject exhibits a reduction in eyelid redness. In some embodiments, the subject exhibits a reduction in eyelid swelling after administration of at least one dose of a polypeptide of the present disclosure. In some embodiments, the subject exhibits a reduction in eyelid hyperemia after administration of at least one dose of a polypeptide of the present disclosure. In some embodiments, the subject exhibits a reduction in ocular itching after administration of at least one dose of a polypeptide of the present disclosure. In some embodiments, the subject exhibits a reduction in visible corneal damage after administration of at least one dose of a polypeptide of the present disclosure. In some embodiments, the subject exhibits a reduction in mucous ocular discharge after administration of at least one dose of a polypeptide of the present disclosure. In some embodiments, the subject exhibits a reduction in watery ocular discharge after administration of at least one dose of a polypeptide of the present disclosure. In some embodiments, the subject exhibits a reduction in tearing after administration of at least one dose of a polypeptide of the present disclosure. In some embodiments, the subject exhibits a reduction in photophobia after administration of at least one dose of a polypeptide of the present disclosure. In some embodiments, the subject exhibits a reduction in foreign body sensation after administration of at least one dose of a polypeptide of the present disclosure. In some embodiments, the subject exhibits a reduction in difficulty opening their eyes after administration of at least one dose of a polypeptide of the present disclosure.In some embodiments, the subject, after administration of at least one dose of a polypeptide of the present disclosure, exhibits a reduction in 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, or 14 symptoms selected from the group consisting of conjunctival redness, conjunctival edema, conjunctival congestion, eyelid redness, eyelid edema, eyelid congestion, itchy eyes, visible corneal damage, mucous eye discharge, watery eye discharge, tearing, photophobia, foreign body sensation, and difficulty opening the eye.

[0237] In some embodiments, the subject exhibits improvement in at least one tissue selected from the group consisting of the conjunctiva, cornea, anterior chamber, iris, pupil, vitreous, and fundus after administration of at least one dose of a polypeptide of the present disclosure. In some embodiments, the subject exhibits improvement in the conjunctiva after administration of at least one dose of a polypeptide of the present disclosure. In some embodiments, the subject exhibits improvement in the cornea after administration of at least one dose of a polypeptide of the present disclosure. In some embodiments, the subject exhibits improvement in the anterior chamber after administration of at least one dose of a polypeptide of the present disclosure. In some embodiments, the subject exhibits improvement in the iris after administration of at least one dose of a polypeptide of the present disclosure. In some embodiments, the subject exhibits improvement in the pupil after administration of at least one dose of a polypeptide of the present disclosure. In some embodiments, the subject exhibits improvement in the vitreous after administration of at least one dose of a polypeptide of the present disclosure. In some embodiments, the subject exhibits improvement in the fundus after administration of at least one dose of a polypeptide of the present disclosure. In some embodiments, the subject exhibits improvement in 2, 3, 4, 5, 6, or 7 tissues selected from the group consisting of the conjunctiva, cornea, anterior chamber, iris, pupil, vitreous, and fundus after administration of at least one dose of a polypeptide of the present disclosure.

[0238] In some embodiments, the subject exhibits an improved inflammation score after administration of at least one dose of a polypeptide of the present disclosure.

[0239] In some embodiments, the subject exhibits improvement in at least one pathological tissue selected from the group consisting of the conjunctiva, cornea, anterior chamber, iris, pupil, vitreous, and fundus after administration of at least one dose of a polypeptide of the present disclosure.

[0240] In some embodiments, the subject exhibits a certain degree of recovery from corneal injury after administration of at least one dose of a polypeptide of the present disclosure.

[0241] In some embodiments, the subject does not experience death attributable to administration of at least one dose of a polypeptide of the present disclosure.

[0242] In some embodiments, the subject does not experience adverse mental states attributable to administration of at least one dose of a polypeptide of the present disclosure.

[0243] In some embodiments, the subject does not experience altered (eg, worsened) behavioral activity attributable to administration of at least one dose of a polypeptide of the present disclosure.

[0244] In some embodiments, the subject does not experience altered (eg, worsened) feeding behavior attributable to administration of at least one dose of a polypeptide of the present disclosure.

[0245] In some embodiments, the subject does not experience altered (eg, worsened) fecal characteristics attributable to administration of at least one dose of a polypeptide of the present disclosure.

[0246] In some embodiments, the subject does not experience weight loss attributable to administration of at least one dose of a polypeptide of the present disclosure.

[0247] In some embodiments, the polypeptides of the present disclosure are administered in the form of an ophthalmic formulation comprising a polypeptide of the present disclosure and a pharmaceutically acceptable excipient.

[0248] In some embodiments, the ophthalmic formulation is formulated as a solution. In some embodiments, the ophthalmic formulation is formulated as an eye drop solution. In some embodiments, the ophthalmic formulation is formulated as a gel. In some embodiments, the ophthalmic formulation is formulated as an ointment. In some embodiments, the ophthalmic formulation is formulated as a suspension, semi-liquid, semi-solid gel, cream, foam gel, contact lens solution, eyewash, etc.

[0249] In some embodiments, the ophthalmic formulation is prepared by dissolving the polypeptide of the present disclosure in an aqueous solution. Aqueous solutions and aqueous diluents that can be used in preparing the ophthalmic formulation include, but are not limited to, distilled water, saline, etc.

[0250] In some embodiments, ophthalmic formulations are prepared by dissolving a polypeptide of the present disclosure in a non-aqueous solution or diluent, including, but not limited to, edible (e.g., vegetable) oil, liquid paraffin, mineral oil, propylene glycol, p-octyldodecanol, polysorbate, macrogol, aluminum monostearate, and the like.

[0251] In some embodiments, ophthalmic formulations are formulated by mixing, diluting, or dissolving the polypeptides of the present disclosure with suitable pharmaceutically acceptable additives, such as disintegrants, binders, lubricants, diluents, buffers, preservatives, wetting agents, emulsifiers, dispersing agents, stabilizers, and solubilizing agents, according to conventional methods in a conventional manner depending on the dosage form.

[0252] In some embodiments, a buffering agent is added to maintain a constant pH, and may include pharmaceutically acceptable buffering agents such as borate buffer, citrate buffer, tartrate buffer, phosphate buffer, acetate buffer, and Tris-HCl buffer (containing tris(hydroxymethyl)aminomethane and HCl). For example, a Tris-HCl buffer having a pH of 7.4 contains 3 g / L tris-(hydroxymethyl)aminomethane and 0.76 g / L HCl. In some embodiments, the buffer is a 10x phosphate buffered saline ("PBS") or 5x PBS solution. The buffering agent is added to the ophthalmic formulation in an amount that provides sufficient buffering capacity for the expected physiological conditions.

[0253] Other buffers that may be used in ophthalmic formulations include HEPES (N-{2-hydroxyethyl}piperazine-N'-{2-ethanesulfonic acid}), which has a pKa of 7.5 at 25°C and a pH in the range of about 6.8 to 8.2; BES (N,N-bis{2-hydroxyethyl(ethy1)}2-aminoethanesulfonic acid), which has a pKa of 7.1 at 25°C and a pH in the range of about 6.4 to 7.8; MOPS (3-{N-morpholino}propanesulfonic acid), which has a pKa of 7.2 at 25°C and a pH in the range of about 6.5 to 7.9; TES (N-tris{hydroxymethyl}-methyl-2-aminoethanesulfonic acid), which has a pKa of 7.4 and a pH in the range of about 6.8 to 8.2; MOBS (4-{N-morpholino}butanesulfonic acid), which has a pKa of 7.6 and a pH in the range of about 6.9 to 8.3 at 25°C; DIPSO (3-(N,N-bis{2-hydroxyethyl}amino)-2-hydroxypropane), which has a pKa of 7.52 and a pH in the range of about 7 to 8.2 at 25°C; and TA, which has a pKa of 7.61 and a pH in the range of about 7 to 8.2 at 25°C. PS ({(2-hydroxy-3{tris(hydroxymethyl)methylamino}-1-propanesulfonic acid)); TAPS ({(2-hydroxy-1,1-bis(hydroxymethyl)ethyl)amino(aminol)-1-propanesulfonic acid)) having a pKa of 8.4 at 25°C and a pH in the range of about 7.7 to 9.1; TABS (N-tris(hydroxymethyl)methyl-4-aminobutanesulfonic acid) having a pKa of 8.9 at 25°C and a pH in the range of about 8.2 to 9.6; AMPSO (N-(1,1-dimethyl-2-hydroxyethyl)-3-amino-2-hydroxypropanesulfonic acid) with a pH in the range of about 8.6-10.0 at 25°C; CHES (2-cyclohexylamino)ethanesulfonic acid with a pKa of 9.5 at 25°C and a pH in the range of about 8.6-10.0; CAPSO (3-(cyclohexylamino)-2-hydroxy-1-propanesulfonic acid) with a pKa of 9.6 at 25°C and a pH in the range of about 8.9-10.3; and CAPSO (3-(cyclohexylamino)-2-hydroxy-1-propanesulfonic acid) with a pKa of 10.4 at 25°C and a pH in the range of about 9.7-11.These include, but are not limited to, buffers based on CAPS (3-(cyclohexylamino)-1-propanesulfonic acid), which have a pH in the range of 1.

[0254] In some embodiments, isotonicity agent can be added to make ophthalmic preparation isotonic with tear fluid.Isotonicity agent includes but is not limited to sugar, such as dextrose, glucose, sucrose and fructose; sugar alcohol, such as mannitol and sorbitol; polyhydric alcohol, such as glycerol, polyethylene glycol and propylene glycol; and salt, such as sodium chloride, sodium citrate, benzalkonium chloride, phedrine chloride, potassium chloride, procaine chloride, chloramphenicol and sodium succinate.Isotonicity agent is added in an amount that makes the osmotic pressure of ophthalmic preparation equal to the osmotic pressure of tear fluid.

[0255] In some embodiments, the ophthalmic formulation comprises a tonicity agent. Suitable tonicity agents for ophthalmic formulations include, but are not limited to, sodium chloride, sodium nitrate, sodium sulfate, sodium bisulfate, potassium chloride, calcium chloride, magnesium chloride, zinc chloride, potassium acetate, sodium acetate, sodium bicarbonate, sodium carbonate, sodium thiosulfate, magnesium sulfate, disodium hydrogen phosphate, sodium dihydrogen phosphate, potassium dihydrogen phosphate, dextrose, mannitol, sorbitol, dextrose, sucrose, urea, propylene glycol, glycerin, and combinations thereof.

[0256] In some embodiments, ophthalmic formulations comprise viscosity enhancer.The viscosity enhancer suitable for ophthalmic formulations includes but is not limited to: monomeric polyols, such as tyloxapol, glycerol, propylene glycol, ethylene glycol; polymeric polyols, such as polyethylene glycol (for example, PEG 300, PEG 400); cellulose-based polymers, such as cellulose gum, alkyl cellulose, hydroxyl-alkyl cellulose, hydroxyl-alkyl alkyl cellulose, carboxy-alkyl cellulose, hydroxyethyl cellulose, hypromellose, hydroxypropyl methylcellulose, methylcellulose, sodium carboxymethylcellulose, hydroxypropyl cellulose; dextran, such as dextran 70; water-soluble protein, such as gelatin; vinyl polymers, such as polyvinyl alcohol, polyvinylpyrrolidine; other polyols, such as polysorbate 80, povidone; polysaccharides and glycosaminoglycans, such as hyaluronan, chondroitin sulfate; and combinations thereof.

[0257] In some embodiments, preservatives may be added to maintain the integrity of the ophthalmic formulation, including, but not limited to, sorbic acid, benzalkonium chloride, benzododecinium bromide, parabens, chlorobutanol, benzyl alcohol, phenylethyl alcohol, edentate disodium, sorbic acid, polyquaternium-1, or other agents known to those skilled in the art.

[0258] In addition to the above, in some embodiments, it may be desirable to use additional agents in ophthalmic formulations, including, but not limited to, stabilizers suitable for ophthalmic formulations, such as, but not limited to, sodium sulfite, sodium carbonate, and propylene glycol; antioxidants, such as, for example, ascorbic acid, sodium ascorbate, butylated hydroxytoluene (BHT), butylated hydroxyanisole (BHA), tocopherol, sodium thiosulfate; and / or chelating agents, such as, for example, ethylene-diamine-tetraacetic acid (EDTA), ethylene glycol-bis-(2-aminoethyl)-N,N,N,N-tetraacetic acid (EGTA), and sodium citrate.

[0259] Eye drops, ophthalmic gels and / or ophthalmic ointments can be prepared by aseptic procedures. Alternatively, sterilization of the composition can be carried out at an appropriate stage of preparation. In some embodiments, a sterile composition can be prepared by aseptically mixing sterile components. In some embodiments, a sterile composition can be prepared by first mixing the components and then sterilizing the final preparation. Sterilization methods can include, but are not limited to, heat sterilization, irradiation and filtration.

[0260] In some embodiments, ophthalmic ointments (eye ointments) can be prepared aseptically by mixing the polypeptide of the present disclosure into a base used for preparing eye ointments using any method known in the art, and then formulating it into a pharmaceutical preparation. Typical bases for eye ointments are exemplified by petrolatum, Jelene 50, Plastibase, and Macrogol. Additionally, surfactants can be added to increase hydrophilicity.

[0261] In some embodiments, additives may be added to ophthalmic formulations, such as eye drops, ophthalmic gels, and / or ophthalmic ointments, as needed, including, but not limited to, further ingredients, additives, carriers suitable for use in contact with or around the eye without undue toxicity, incompatibility, instability, irritation, allergic response, etc.

[0262] In some embodiments, the ophthalmic formulation is formulated for topical administration. In some embodiments, the ophthalmic formulation can be administered locally to the eye, for example, subconjunctivally, retrobulbarly, periocularly, subretinally, suprachoroidally, or intraocularly.

[0263] In some embodiments, the ophthalmic formulation may be delivered to the ocular surface, interconnecting innervation, conjunctiva, lacrimal gland, or meibomian gland. It is contemplated that effective treatment may include administering a polypeptide of the present disclosure via oral administration, topical administration, via injection, intranasally, rectally, transdermally, via an impregnated or coated device, e.g., an ocular insert or implant, or iontophoretically, among other routes of administration.

[0264] In some embodiments, the ophthalmic formulation is formulated for injection. For administration via injection, the ophthalmic formulation can be injected intramuscularly, intraarterially, subcutaneously or intravenously. A pump mechanism can be used to administer the ophthalmic formulation over a preselected period of time. For some embodiments of the present invention, it is desirable to deliver the drug locally, and therefore the injection is performed periocularly, intraocularly, subconjunctivally, retrobulbarly or intracamerally.

[0265] In some embodiments, the ophthalmic formulation can be administered to the ocular surface via a pump-catheter system or can be released internally from a continuous or selective release device, such as, but not limited to, a membrane, such as that used in the Ocusert™ System (Alza Corp, Palo Alto, CA). The ophthalmic formulation can be incorporated into, carried by, or attached to a contact lens that is then worn by the subject. The ophthalmic formulation can be sprayed onto the ocular surface.

[0266] In some embodiments, the ophthalmic formulation comprises from about 0.001 μM to about 100 μM of a polypeptide of the present disclosure. In some embodiments, the ophthalmic formulation comprises from about 0.01 μM to about 20 μM of a polypeptide of the present disclosure. In some embodiments, the ophthalmic formulation comprises from about 0.1 μM to about 5 μM of a polypeptide of the present disclosure. In some embodiments, the ophthalmic formulation comprises from about 0.2 μM to about 3 μM of a polypeptide of the present disclosure. In some embodiments, the ophthalmic formulation comprises from about 0.1 μM to about 10 μM of a polypeptide of the present disclosure. In some embodiments, the ophthalmic formulation comprises from about 1 μM to about 5 μM of a polypeptide of the present disclosure. In some embodiments, the ophthalmic formulation comprises from about 1 μM to about 10 μM of a polypeptide of the present disclosure. In some embodiments, the ophthalmic formulation comprises from about 5 μM to about 10 μM of a polypeptide of the present disclosure. In some embodiments, the ophthalmic formulation comprises from about 10 μM to about 50 μM of a polypeptide of the present disclosure. In some embodiments, the ophthalmic formulation comprises about 20 μM to about 50 μM of a polypeptide of the present disclosure. In some embodiments, the ophthalmic formulation comprises about 5 μM to about 50 μM of a polypeptide of the present disclosure. In some embodiments, the ophthalmic formulation comprises about 1 μM to about 50 μM of a polypeptide of the present disclosure. In some embodiments, the ophthalmic formulation comprises about 1 μM to about 20 μM of a polypeptide of the present disclosure. In some embodiments, the ophthalmic formulation comprises about 5 μM to about 20 μM of a polypeptide of the present disclosure. In some embodiments, the ophthalmic formulation comprises about 10 μM to about 20 μM of a polypeptide of the present disclosure. In some embodiments, the ophthalmic formulation comprises more than about 0.001, 0.05, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2.0, 2.1, 2.2, 2.3, 2.4, 2.5, 2.6, 2.7, 2.8, 2.9, or 3.0 μM of a polypeptide of the present disclosure. In some embodiments, the ophthalmic formulation comprises less than about 100, 90, 80, 70, 60, 50, 40, 30, 20, 25, 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, or 4 μM of a polypeptide of the present disclosure.

[0267] In some embodiments, the ophthalmic formulations may be formulated into dosage forms of about 0.01 to about 10 ml for single or multiple uses. In some embodiments, the ophthalmic formulations may be formulated into unit dosage forms to provide a total daily dosage of about 0.01 to about 2 ml. In some embodiments, the ophthalmic formulations may be formulated into unit dosage forms to provide a total weekly dosage of about 1 ml to about 5 ml. In some embodiments, the ophthalmic formulations may be formulated into unit dosage forms to provide a total monthly dosage of about 1 ml to about 20 ml.

[0268] In some embodiments, the ophthalmic formulation is an ophthalmic formulation for use in humans.

[0269] In some embodiments, the ophthalmic formulation is a veterinary ophthalmic formulation.

[0270] In some embodiments, the methods of the present disclosure include administering an effective amount of a polypeptide of the present disclosure to one affected eye or ocular tissue of a subject. In some embodiments, the methods of the present disclosure include administering an effective amount of a polypeptide of the present disclosure to both eyes or ocular tissues of a subject. In some embodiments, the effective amount of polypeptide of the present disclosure is about 0.1 μg to about 100 μg per eye, or about 0.1 μg to about 50 μg per eye, or about 0.1 μg to about 20 μg per eye, or about 0.1 μg to about 10 μg per eye, or about 0.5 μg to about 50 μg per eye, or about 0.5 μg to about 20 μg per eye, or about 0.5 μg to about 10 μg per eye, or about 1 μg to about 10 μg per eye.

[0271] In some embodiments, the dosage for one eye of a subject may be about 1 to about 5 drops of ophthalmic formulation. In some embodiments, the dosage for one eye of a subject may be one drop of ophthalmic formulation. In some embodiments, the dosage for one eye of a subject may be two drops of ophthalmic formulation. In some embodiments, the dosage for one eye of a subject may be three drops of ophthalmic formulation. In some embodiments, the dosage for one eye of a subject may be four drops of ophthalmic formulation. In some embodiments, the dosage for one eye of a subject may be five drops of ophthalmic formulation. In some embodiments, each drop corresponds to about 10 μL to about 150 μL. In some embodiments, each drop corresponds to about 20 μL to about 70 μL.

[0272] In some embodiments, the method of the present disclosure comprises administering an effective amount of an ophthalmic formulation to each eye of a subject once a day. In some embodiments, the method of the present disclosure comprises administering an effective amount of an ophthalmic formulation to each eye of a subject twice a day. In some embodiments, the method of the present disclosure comprises administering an effective amount of an ophthalmic formulation to each eye of a subject three or more times a day. In some embodiments, the method of the present disclosure comprises administering an effective amount of an ophthalmic formulation to each eye of a subject every two days. In some embodiments, the method of the present disclosure comprises administering an effective amount of an ophthalmic formulation to each eye of a subject every three days. In some embodiments, the method of the present disclosure comprises administering an effective amount of an ophthalmic formulation to each eye of a subject every week.

[0273] In some embodiments, the method of the present disclosure comprises administering one or more drops of the ophthalmic formulation to each eye of the subject every day. In some embodiments, the method of the present disclosure comprises administering one to more drops of the ophthalmic formulation to each eye of the subject 2, 3, 4, 8, 12, 18 or 24 times a day. In some embodiments, the method of the present disclosure comprises administering one or more drops of the ophthalmic formulation to each eye of the subject every two days.

[0274] In some embodiments, the polypeptides or ophthalmic formulations of the present disclosure can be arranged in a kit. In some embodiments, the kit includes one or more of the polypeptides or ophthalmic formulations of the present disclosure and instructions for using the kit.

[0275] The kit may include one or more containers containing one or more of the polypeptides or ophthalmic formulations of the present disclosure.The polypeptides of the present disclosure may be present in the container as prepared formulations, or alternatively, the polypeptides of the present disclosure may be unformulated.In some embodiments, the kit may include the unformulated polypeptides of the present disclosure in a container separate from the pharmaceutically acceptable additives.Before use, the polypeptides of the present disclosure are diluted with or otherwise mixed with the pharmaceutically acceptable additives.

[0276] In some embodiments, the kit also includes instructions describing a method for administering the polypeptide or ophthalmic formulation of the present disclosure. In some embodiments, the instructions also describe a procedure for mixing the polypeptide of the present disclosure contained in the kit with a pharmaceutically acceptable excipient.

[0277] Preparation of Polypeptides Polypeptides of the present disclosure, such as artificial polypeptides of Formula (I), (II), (III), (IV), (V), (VI) or (VII), or variants of artificial polypeptides of Formula (I), (II), (III), (IV) or (V), or polypeptides having at least 70% identity (e.g., at least 80% identity) to any one selected from SEQ ID NO: 28, SEQ ID NO: 57, and SEQ ID NO: 62-74, or fragments or variants thereof, can be prepared by any suitable method, including, but not limited to, molecular cloning techniques and synthetic procedures. Standard molecular cloning techniques are well known in the art and are described by Sambrook, J., Fritsch, E. F. and Maniatis, T. Molecular Cloning: A Laboratory Manual; Cold Spring Harbor Laboratory Press: Cold Spring Harbor, (1989) (Maniatis) and T. J. Silhavy, M. L. Bennan, and L. W. Enquist, Experiments with Gene Fusions, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY (1984) and Ausubel, F. M. et al., Current Protocols in Molecular Biology, pub. by Greene Publishing Assoc. and Wiley-Interscience (1987).

[0278] In some embodiments, the polypeptide of the present disclosure is prepared by referring to the fermentation-based production method disclosed in Chinese Patent Application No. 201711320516.4 (Publication No.: CN109913483A), the entire contents of which are incorporated herein by reference. In some embodiments, the method for preparing the polypeptide of the present disclosure includes the steps of: incorporating a target gene fragment into an expression plasmid by genetic engineering, wherein the incorporated target gene fragment comprises at least one purification tag; transforming the expression plasmid into a corresponding expression host to construct a recombinant engineered cell that highly expresses the target polypeptide; subjecting the recombinant engineered cell to fermentation, induced expression, and then crude purification to obtain a crude polypeptide; subjecting the crude polypeptide to precision purification to obtain a highly purified polypeptide.

[0279] In some embodiments, the target gene fragment is a gene fragment capable of encoding a polypeptide of the present disclosure, e.g., an artificial polypeptide of Formula (I), (II), (III), (IV), (V), (VI), or (VII), or a variant of an artificial polypeptide of Formula (I), (II), (III), (IV), or (V), or a polypeptide having at least 70% identity (e.g., at least 80% identity) to any one selected from SEQ ID NO: 28, SEQ ID NO: 57, and SEQ ID NOs: 62-74, or a fragment or variant thereof. In some embodiments, the target gene fragment is a gene fragment capable of encoding an artificial polypeptide of Formula (I), (II), (III), (IV), (V), (VI), or (VII). In some embodiments, the target gene fragment is a gene fragment capable of encoding a variant of an artificial polypeptide of Formula (I), (II), (III), (IV), or (V). In some embodiments, the target gene fragment is a gene fragment capable of encoding a polypeptide having at least 70% identity (e.g., at least 80% identity) to any one selected from SEQ ID NOs: 28, 57, and 62-74, or a fragment or variant thereof. The target gene fragment may be prepared by any suitable method, including, but not limited to, enzymatic synthesis, i.e., using RNA as a template to synthesize cDNA by reverse transcription, and chemical synthesis, i.e., using chemical methods, or chemical methods in combination with enzymatic methods, to synthesize the target gene. Preparation of the target gene fragment may also be performed commercially by a contract research organization (CRO) if the sequence of the target gene fragment is provided.

[0280] In some embodiments, the purification tag is an ST sequence tag (an amino acid sequence that helps the polypeptides of the disclosure form inclusion bodies) or a His tag.

[0281] In some embodiments, the expression host is a host cell. A host cell includes, but is not limited to, an individual cell, a cell culture, or a cell line. In some embodiments, a host cell includes the progeny of a single host cell. In some embodiments, a host cell can be transfected with a heterologous sequence comprising a vector encoding a polypeptide of the present disclosure. In some embodiments, the host cell can be a prokaryotic cell, such as a bacterial cell. In some embodiments, the host cell can be a eukaryotic cell, such as a yeast cell, an animal cell, an insect cell, a plant cell, etc.

[0282] Examples of bacterial host cells that can be used to produce the polypeptides or variants of the present disclosure include microorganisms belonging to the genera Escherichia, Serratia, Bacillus, Brevibacterium, Corynebacterium, Microbacterium, Pseudomonas, etc. For example, bacterial host cells can include, but are not limited to, Escherichia coli XL1-Blue, XL2-Blue, DH1, MC1000, KY3276, W1485, JM109, HB101, No. 49, i W3110, NY49, G1698, BL21, or TB1. Other bacterial host cells include Serratia ficaria, Serratia fonticola, Serratia liquefaciens, Serratia marcescens, Bacillus subtilis, Bacillus amyloliquefaciens, Brevibacterium ammoniagenes, Brevibacterium immariophilum ATCC 14068, Brevibacterium saccharolyticum ATCC 14066, Brevibacterium flavum ATCC 14067, Brevibacterium lactofermentum ATCC 13869, Corynebacterium glutamicum ATCC 13032, Corynebacterium glutamicum ATCC 13869, Corynebacterium acetoacidophilum ATCC 13870, Microbacterium ammoniaphilum ATCC 15354, Pseudomonas putida, Pseudomonas sp. D-0110, and the like.

[0283] Examples of yeast cells that can be used to produce polypeptides of the present disclosure include microorganisms belonging to the genera Kluyveromyces, Trichosporon, Saccharomyces, Schizosaccharomyces, Schwanniomyces, Pichia, Candida, etc., such as Saccharomyces cerevisiae, Schizosaccharomyces pombe, Kluyveromyces lactis, Trichosporon pullulans, Schwanniomyces alluvius, Candida utilis, etc.

[0284] Examples of animal cells that can be used to produce the polypeptides of the present disclosure include mammalian cells, such as Chinese hamster ovary cells (CHO) or monkey cells, such as COS cells, HepG2 cells, A549 cells, and any other cells available through the ATCC or other depository organization.

[0285] In some embodiments, the expression host is an Escherichia coli host cell. In some embodiments, the fermentation medium used in the fermentation process has the following composition: yeast extract powder 10-50 g / L, peptone 10-30 g / L, ammonium sulfate 2-10 g / L, sodium chloride 2-10 g / L, potassium dihydrogen phosphate 0-10 g / L, dipotassium hydrogen phosphate 2-15 g / L, antifoam 0.01-0.1% (v / v), FeSO4·7H2O 0-0.1 g / L, ZnSO4·7H2O 0-0.02 g / L, CuSO4·5H2O 0-0.1 g / L, MnSO4·5H2O 0-0.05 g / L, CaCl2·7H2O 0-0.01 g / L, CoCl2·6H2O 0-0.01 g / L, Na2MoO4·2H2O 0-0.01 g / L, HBO 0-0.0005 g / L, and biotin 0-0.005 g / L. In some embodiments, the fermentation process is carried out at 37°C.

[0286] In some embodiments, induced expression is achieved by the addition of isopropyl-beta-D-thiogalactopyranoside (IPTG) during the fermentation process. In some embodiments, IPTG is added 0.5, 1, 2, 3, 4, or 5 hours after the start of the fermentation process. In some embodiments, IPTG is added to a final concentration of 0.25, 0.5, 1, 2, or 4 mM. In some embodiments, induced expression is performed at 37°C.

[0287] The crude purification of the present disclosure is a process in which the culture produced by the fermentation process is preliminarily treated. In some embodiments, crude purification includes the steps of collecting cells, lysing the cells, and then isolating inclusion body proteins and / or cytoplasmic proteins; subjecting the inclusion body proteins and / or cytoplasmic proteins to denaturation, renaturation, and enzymatic digestion to obtain a crude product containing the crude polypeptide. In some embodiments, crude purification includes the steps of collecting the culture medium, removing cells and impurities, and obtaining the supernatant, i.e., the crude product containing the crude polypeptide.

[0288] The precision purification of the present disclosure is the process that the crude product containing crude polypeptide is purified by chromatography.The example of the chromatography method that can be used for purifying the polypeptide of the present disclosure includes: ion exchange chromatography that uses strong anion exchange resin, weak anion exchange resin or multimodal anion exchange resin; affinity chromatography; reversed-phase chromatography that uses reversed-phase packing material; molecular sieve chromatography that uses size exclusion packing material; and hydrophobic chromatography that uses hydrophobic packing material.

[0289] More detailed information for preparing the polypeptides of the present disclosure can be found throughout the disclosure of CN109913483A, for example, in Examples 1-4.

[0290] While preferred embodiments of the present invention have been shown and described herein, it will be apparent to those skilled in the art that such embodiments are provided by way of example only. It is not intended that the present invention be limited by the specific examples provided herein. While the present invention has been described with reference to the above specification, the description and illustration of the embodiments herein are not meant to be construed in a limiting sense. Numerous variations, changes, and substitutions will now occur to those skilled in the art without departing from the invention. Furthermore, it should be understood that all aspects of the present invention are not limited to the specific depictions, configurations, or relative proportions set forth herein, which depend upon a variety of conditions and variables. It should be understood that various alternatives to the embodiments of the present invention described herein may be employed in practicing the present invention. It is therefore intended that the present invention also cover any such alternatives, modifications, variations, or equivalents. It is intended that the following claims define the scope of the invention, and that methods and structures within the scope of these claims and their equivalents be covered thereby. [Example]

[0291] The present disclosure will now be described with reference to the following examples, which are intended to illustrate but not limit the invention.

[0292] Unless otherwise specified, if specific conditions are not given in the examples, they are carried out according to conventional conditions or conditions suggested by the manufacturer. Reagents or equipment used without manufacturer's instructions are commercially available conventional products. Those skilled in the art will understand that the examples described herein are not intended to limit the scope of the claimed invention.

[0293] Example 1 Efficacy of polypeptides of the present disclosure on the treatment of chicken ovalbumin (OVA)-induced allergic conjunctivitis in New Zealand rabbits The purpose of this example is to investigate the effect of the polypeptide of the present disclosure on the treatment of allergic conjunctivitis.For this purpose, chicken ovalbumin (OVA) is used as an allergen to induce specific immune response in New Zealand rabbits, causing the symptoms of allergic conjunctivitis to appear in the rabbit's eyes.Then, the polypeptide of the present disclosure is administered to rabbits to study whether these polypeptides have a certain therapeutic effect on allergic conjunctivitis in rabbits.

[0294] animal

[0295] Forty-two New Zealand rabbits, weighing approximately 2.0-3.5 kg (6-8 weeks old), were used. Of these, 30 rabbits, both male and female, were selected for enrollment in the study.

[0296] modeling

[0297] In this study, 200 μg of OVA was injected subcutaneously every 5 days. Meanwhile, 80 μg / μl of OVA was administered to each eye daily for 5 days during the first week. After a 1-day washout period, ocular OVA administration continued for 3 days, followed by another 1-day washout period to reinforce sensitization. From approximately D11 to D15 after modeling, rabbits began to show symptoms such as conjunctival edema, conjunctival hyperemia, eyelid edema, eyelid hyperemia, visible corneal damage, mucous eye discharge, tearing, and difficulty opening the eyes. This demonstrated successful modeling of allergic conjunctivitis.

[0298] Grouping and Dosing

[0299] After 12 days of modeling and verification by slit lamp photography and eye irritation test, the rabbits were randomly divided into the following three groups with 10 animals in each group: 20 eyes of the rabbits were subjected to the procedures shown in Table 1.

[0300] [Table 1] *: The final dosage design should be determined according to the method of administration of the test substance(s). #: Subcutaneous injection of OVA + ophthalmic administration of OVA was stopped on D19 after modeling.

[0301] Briefly, dosing was performed according to the procedures shown in Table 1, starting on D12 after modeling (depending on the specific situation) and continuing for two weeks, one week for dosing while modeling and one week for dosing during the recovery period after the end of modeling.

[0302] Eye test items

[0303] The following ocular examination items were performed according to the detailed descriptions provided in Table 2.

[0304] [Table 2]

[0305] statistical analysis

[0306] The inflammation scores obtained in the study, the pathological tissues collected, and the results of the detection of recovery from corneal injury were subjected to statistical analysis.

[0307] Example 2 Effect of polypeptides of the present disclosure on the treatment of allergic conjunctivitis induced by chicken ovalbumin (OVA) in mice The purpose of this example is to investigate the effect of the polypeptide of the present disclosure on the treatment of allergic conjunctivitis.For this purpose, chicken ovalbumin (OVA) is used as an allergen to induce specific immune response in mice, and after challenge, the symptoms of allergic conjunctivitis occur in the eyes of mice.Then, the polypeptide of the present disclosure is administered to mice to study whether these polypeptides have a certain therapeutic effect on allergic conjunctivitis in mice.

[0308] modeling

[0309] Female 6-week-old mice were selected for enrollment in this study. In this study, mice were subcutaneously injected with OVA on day 0 to induce sensitization. The sensitization procedure was repeated on day 5 to enhance the allergic response. OVA was administered to each eye as a challenge every other day from days 10 to 14. After challenge, the mice exhibited symptoms such as conjunctival edema, conjunctival hyperemia, eyelid edema, eyelid hyperemia, visible corneal damage, mucous ocular discharge, lacerations, and difficulty in opening the eyes. This demonstrated successful modeling of allergic conjunctivitis.

[0310] Grouping and Dosing

[0311] The mice were randomly divided into the following three groups (N=10 per group): The eyes of the mice were subjected to the procedures shown in Table 3.

[0312] [Table 3]

[0313] Briefly, administration was performed according to the procedures shown in Table 3, starting on D9 and continuing for 1 week.

[0314] Eye test items

[0315] Mice underwent general eye examination once daily during the administration period. Specifically, conjunctival edema, mucous discharge, and conjunctival redness were graded from 0 to 4 (0: absent; 1: minimal; 2: mild; 3: moderate; 4: severe) based on the criteria set forth in Merayo-Lloves J, Zhao TZ, Dutt JE, Foster CS. A new murine model of allergic conjunctivitis and effectiveness of nedocromil sodium. J Allergy Clin Immunol 1996; 97:1129-40 (see, e.g., Table 1). The inflammation score of each mouse was calculated as the sum of three independent scores. Furthermore, the number of scratches was assessed after challenge. The scratch response was defined as a rapid movement of the hind paws toward the eye. After the final administration, the mice were euthanized, and tissues and blood were collected for further study (data not shown).

[0316] result

[0317] Figure 1 shows the inflammation scores of mice from each group on day 14. The inflammation score indicates the degree of inflammation in the eye, which is used to evaluate allergic conjunctivitis. It was found that the inflammation scores of both the SEQ ID NO: 29 group and the SEQ ID NO: 89 group were significantly lower than those of the control group (SEQ ID NO: 29, p<0.0001; SEQ ID NO: 89, p<0.01). These results indicated that the polypeptide of the present disclosure can significantly improve the symptoms of allergic conjunctivitis.

[0318] Figure 2 shows the number of scratchings of mice from each group on day 14. The number of scratchings indicates the severity of allergic conjunctivitis symptoms. It was found that the number of scratchings was significantly lower in the SEQ ID NO: 29 group and SEQ ID NO: 89 group compared to the control group (SEQ ID NO: 29, p<0.01; SEQ ID NO: 89, p<0.01), indicating that treatment with the polypeptide of the present disclosure can significantly reduce the number of scratchings. These results indicated that the polypeptide of the present disclosure has a clear therapeutic effect on allergic conjunctivitis. Table 4-1 Table 4-2 Table 4-3 Table 4-4

Claims

1. 1. A method for treating or preventing allergic conjunctivitis in a subject in need thereof, comprising administering an effective amount of an artificial polypeptide of formula (I): X-Y (I) to said subject, wherein: X is a moiety comprising a sequence having at least 80% identity with 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 contains a total number of cysteines (C) of less than 5; method.

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

1.

3. 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. 4. The method of claim 1, wherein Y comprises a total number of cysteines (C) of less than 4, or Y comprises a total number of cysteines (C) of less than 3, or Y comprises a total number of cysteines (C) of less than 2.

5. 5. The method of claim 1 , 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 5 or less.

6. 6. The method of any one of claims 1 to 5, wherein X comprises a sequence having at least 90% identity to any one selected from SEQ ID NOs: 81 to 83.

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

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

9. 9. The method according to 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 phlyctenular keratoconjunctivitis.

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

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

13. 13. The method of claim 12, wherein the perennial allergen is at least one selected from the group consisting of house dust mites, cockroaches, and animal dander.

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

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

16. 16. The method of claim 15, 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 a protruding scleral buckle, and elevated corneal scars.

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

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

19. 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 viridians, Mycobacterium tuberculosis), viruses (e.g., herpes simplex virus), chlamydia, fungi (e.g., Candida, e.g., Candida albicans), and parasites (e.g., tapeworms, e.g., Hymenolepis nana; and nematodes).

20. 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 a dry eye-related disorder.

21. 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 congestion, eyelid redness, eyelid edema, eyelid congestion, itchy eyes, visible corneal damage, mucous eye discharge, watery eye discharge, tearing, photophobia, foreign body sensation, and difficulty opening the eyes prior to administration of the artificial polypeptide of Formula (I).

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

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

24. 1. A method for treating or preventing allergic conjunctivitis in a subject in need thereof, comprising administering an effective amount of an artificial polypeptide of formula (II): X-Y (II) to said subject, wherein: X is a moiety comprising a sequence having at least 80% identity with 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 having at most 90% identity to SEQ ID NO:2; method.

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

1.

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

2.

28. 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 5 or less.

29. 29. The method of any one of claims 24 to 28, wherein Y comprises a sequence having at least 90% identity to any one selected from SEQ ID NOs: 16 to 18, or wherein Y comprises a sequence having at least 95% identity to any one selected from SEQ ID NOs: 16 to 18.

30. 30. The method of any one of claims 24 to 29, wherein the polypeptide comprises a sequence having at least 90% identity to any one selected from SEQ ID NOs: 42 to 44.

31. 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 phlyctenular keratoconjunctivitis.

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

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

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

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

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

38. 38. The method of claim 37, 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 a protruding scleral buckle, and elevated corneal scars.

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

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

41. 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 viridians, Mycobacterium tuberculosis), viruses (e.g., herpes simplex virus), chlamydia, fungi (e.g., Candida, e.g., Candida albicans), and parasites (e.g., tapeworms, e.g., Hymenolepis nana; and nematodes).

42. 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 a dry eye-related disorder.

43. 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 congestion, eyelid redness, eyelid edema, eyelid congestion, itchy eyes, visible corneal damage, mucous eye discharge, watery eye discharge, tearing, photophobia, foreign body sensation, and difficulty opening the eye prior to administration of the artificial polypeptide of formula (II).

44. 44. The method of any one of claims 24 to 43, wherein the subject exhibits a reduction in at least one symptom selected from the group consisting of conjunctival redness, conjunctival edema, conjunctival congestion, eyelid redness, eyelid edema, eyelid congestion, itchy eyes, visible corneal damage, mucous eye discharge, watery eye 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. 45. The method of any one of claims 24 to 44, wherein the subject exhibits improvement in at least one tissue selected from the group consisting of the conjunctiva, cornea, anterior chamber, iris, pupil, vitreous, and fundus after administration of at least one dose of the artificial polypeptide of Formula (II).

46. 1. A method for treating or preventing allergic conjunctivitis in a subject in need thereof, comprising administering an effective amount of an artificial polypeptide of formula (III): X-Y (III) to said subject, wherein: X is a moiety comprising 40-65 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 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; method.

47. 47. The method of claim 46, wherein Y comprises a sequence having at least 90% identity to SEQ ID NO:2, or Y comprises a sequence having at least 95% identity to SEQ ID NO:2, or Y comprises the sequence of SEQ ID NO:

2.

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

49. 49. The method of 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, or 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. 50. The method of 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 15 or less, and / or the total number of hydrophobic amino acids in X is 10 or less.

51. 51. The method of any one of claims 46 to 50, wherein X comprises a sequence having at least 90% identity to any one selected from SEQ ID NOs: 23 to 27, or wherein X comprises a sequence having at least 95% identity to any one selected from SEQ ID NOs: 23 to 27.

52. 52. The method of any one of claims 46 to 51, wherein the polypeptide comprises a sequence having at least 90% identity to any one selected from SEQ ID NOs: 49 to 53.

53. 53. The method of any one of claims 46 to 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 phlyctenular keratoconjunctivitis.

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

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

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

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

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

60. 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 a protruding scleral buckle, and elevated corneal scars.

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

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

63. 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 viridians, Mycobacterium tuberculosis), viruses (e.g., herpes simplex virus), chlamydia, fungi (e.g., Candida, e.g., Candida albicans), and parasites (e.g., tapeworms, e.g., Hymenolepis nana; and nematodes).

64. 64. The method of any one of claims 46 to 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 a dry eye-related disorder.

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

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

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

68. 1. A method for treating or preventing allergic conjunctivitis in a subject in need thereof, comprising administering an effective amount of an artificial polypeptide of formula (IV): X-Y(IV) to said subject, wherein: X is a moiety comprising 40-65 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 having at least 80% identity with SEQ ID NO: 2; X comprises a sequence having at most 90% identity to SEQ ID NO: 1; method.

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

1.

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

2.

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

72. 72. The method of 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 15 or less, and / or the total number of hydrophobic amino acids in X is 10 or less.

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

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

75. 75. The method of any one of claims 68 to 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 phlyctenular keratoconjunctivitis.

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

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

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

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

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

82. 82. The method of claim 81, 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 a protruding scleral buckle, and elevated corneal scars.

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

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

85. 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 viridians, Mycobacterium tuberculosis), viruses (e.g., herpes simplex virus), chlamydia, fungi (e.g., Candida, e.g., Candida albicans), and parasites (e.g., tapeworms, e.g., Hymenolepis nana; and nematodes).

86. 86. The method of any one of claims 68 to 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 a dry eye-related disorder.

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

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

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

90. 1. A method for treating or preventing allergic conjunctivitis in a subject in need thereof, comprising administering an effective amount of an artificial polypeptide of formula (V): X-Y (V) to said subject, wherein: X is a moiety comprising a sequence having at least 80% identity with SEQ ID NO: 1; Y is a moiety comprising 10 to 30 amino acids, and Y comprises a sequence having at least 10 consecutive AA of SEQ ID NO:2; method.

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

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

1.

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

96.

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

2.

96. 96. The method of any one of claims 90 to 95, wherein Y comprises a sequence having at least 80% identity to any one selected from SEQ ID NOs: 97-103, or Y comprises a sequence having at least 90% identity to any one selected from SEQ ID NOs: 97-103, or Y comprises a sequence having at least 95% identity to any one selected from SEQ ID NOs: 97-103.

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

98. 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 phlyctenular keratoconjunctivitis.

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

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

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

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

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

105. 105. The method of claim 104, 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 a protruding scleral buckle, and elevated corneal scars.

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

107. 99. The method of claim 98, wherein the phlyctenular keratoconjunctivitis is caused or partially caused by a delayed-type hypersensitivity or 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 viridians, Mycobacterium tuberculosis), viruses (e.g., herpes simplex virus), chlamydia, fungi (e.g., Candida, e.g., Candida albicans), and parasites (e.g., tapeworms, e.g., Hymenolepis nana; and nematodes).

109. 109. The method of any one of claims 90 to 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 a dry eye-related disorder.

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

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

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

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

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

1.

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

2.

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

117. 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 is less than or equal to 20.

118. 118. The method of 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 is 20 or less.

119. 119. The method of any one of claims 113 to 118, wherein X comprises a sequence having at least 80% identity to any one selected from SEQ ID NOs: 80 to 83, or wherein X comprises a sequence which is any one selected from SEQ ID NOs: 80 to 83, or wherein X is a sequence which is any one selected from SEQ ID NOs: 80 to 83.

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

3.

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

122. 122. The method of any one of claims 113 to 121, 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 phlyctenular keratoconjunctivitis.

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

124. 124. The method of claim 123, wherein the seasonal allergen is at least one selected from the group consisting of tree pollen, weed pollen, grass pollen, and mold spores.

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

126. 126. The method of claim 125, wherein the perennial allergen is at least one selected from the group consisting of house dust mites, cockroaches, and animal dander.

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

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

129. 129. The method of claim 128, 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 a protruding scleral buckle, and elevated corneal scars.

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

131. 123. The method of claim 122, wherein the phlyctenular keratoconjunctivitis is caused or partially caused by a delayed-type hypersensitivity or inflammatory reaction 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 the group consisting of bacteria (e.g., Staphylococcus aureus, Streptococcus viridians, Mycobacterium tuberculosis), viruses (e.g., herpes simplex virus), chlamydia, fungi (e.g., Candida, e.g., Candida albicans), and parasites (e.g., tapeworms, e.g., Hymenolepis nana; and nematodes).

133. 133. The method of any one of claims 113 to 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 a dry eye-related disorder.

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

135. 135. The method of any one of claims 113 to 134, wherein the subject exhibits a reduction in at least one symptom selected from the group consisting of conjunctival redness, conjunctival edema, conjunctival congestion, eyelid redness, eyelid edema, eyelid congestion, itchy eyes, visible corneal damage, mucous eye discharge, watery eye discharge, tearing, photophobia, foreign body sensation, and difficulty opening the eyes after administration of at least one dose of the artificial polypeptide of formula (VI).

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

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

138. 138. The method of claim 137, wherein the amino acid insertion is located N-terminal to X and / or the inserted amino acid is M.

139. 139. The method of claim 137 or 138, wherein Y, is a moiety comprising a variant of the sequence of SEQ ID NO: 2, said variant 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 acids truncated compared to SEQ ID NO: 2, optionally wherein 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 acids truncated is located at the C-terminus of Y,.

140. 140. The method of 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. 141. The method of 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. 142. The method of 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 is 20 or less.

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

144. 144. The method of any one of claims 137 to 143, wherein 40-65% of the amino acids of Y are selected from I, V, L, F, C, M and A.

145. 145. The method of 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 is 10 or less, and / or the total number of W, Y, F, M, L, I and V in Y is 15 or less.

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

96.

147. 147. The method of any one of claims 137 to 146, wherein Y comprises a sequence having at least 80% identity to any one selected from SEQ ID NOs: 97 to 103, or Y comprises a sequence which is any one selected from SEQ ID NOs: 97 to 103, or Y is a sequence which is any one selected from SEQ ID NOs: 97 to 103.

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

149. 149. The method of any one of claims 137 to 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 phlyctenular keratoconjunctivitis.

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

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

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

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

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

156. 156. The method of claim 155, 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 a protruding scleral buckle, and elevated corneal scars.

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

158. 150. The method of claim 149, wherein the phlyctenular keratoconjunctivitis is caused or partially caused by delayed hypersensitivity or inflammatory reactions 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 the group consisting of bacteria (e.g., Staphylococcus aureus, Streptococcus viridians, Mycobacterium tuberculosis), viruses (e.g., herpes simplex virus), chlamydia, fungi (e.g., Candida, e.g., Candida albicans), and parasites (e.g., tapeworms, e.g., Hymenolepis nana; and nematodes).

160. 160. The method of any one of claims 137 to 159, 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 a dry eye-related disorder.

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

162. 162. The method of any one of claims 137 to 161, wherein the subject exhibits a reduction in at least one symptom selected from the group consisting of conjunctival redness, conjunctival edema, conjunctival congestion, eyelid redness, eyelid edema, eyelid congestion, itchy eyes, visible corneal damage, mucous eye discharge, watery eye discharge, tearing, photophobia, foreign body sensation, and difficulty opening the eyes after administration of at least one dose of the artificial polypeptide of formula (VII).

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

164. 1. A method for treating or preventing allergic conjunctivitis in a subject in need thereof, comprising administering an effective amount of an artificial polypeptide of formula (I). X-Y (I) to said subject a variant of X is a moiety comprising a sequence having at least 80% identity with 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) of less than 5, said mutants being characterized in that they have at least 1, 2, 3, 4, 5, 6, 7, 8 or 9 Ds in X that are mutated to S, and / or at least 1, 2, 3, 4, 5 or 6 Es in X that are mutated to T, method.

165. 165. The method of claim 164, wherein at least 20% of the amino acids of X are selected from R, K, N, D, Q, E and H; at least 30% of the amino acids of X are selected from R, K, N, D, Q, E and H; at most 90% of the amino acids of X are selected from R, K, N, D, Q, E and H; and / or at most 80% of the amino acids of X are selected from R, K, N, D, Q, E and H.

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

1.

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

168. 168. The method of 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, is 5 or less.

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

170. 170. The method of any one of claims 164 to 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 phlyctenular keratoconjunctivitis.

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

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

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

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

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

177. The method of claim 176, 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 a protruding scleral buckle, and elevated corneal scars.

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

179. 171. The method of claim 170, wherein the phlyctenular keratoconjunctivitis is caused or partially caused 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 the group consisting of bacteria (e.g., Staphylococcus aureus, Streptococcus viridians, Mycobacterium tuberculosis), viruses (e.g., herpes simplex virus), chlamydia, fungi (e.g., Candida, e.g., Candida albicans), and parasites (e.g., tapeworms, e.g., Hymenolepis nana; and nematodes).

181. 181. The method of any one of claims 164 to 180, 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 a dry eye-related disorder.

182. The method of any one of claims 164 to 181, wherein the subject experiences at least one symptom selected from the group consisting of conjunctival redness, conjunctival edema, conjunctival congestion, eyelid redness, eyelid edema, eyelid congestion, itchy eyes, visible corneal damage, mucous eye discharge, watery eye discharge, tearing, photophobia, foreign body sensation, and difficulty opening the eyes prior to administration of the variant of the artificial polypeptide of formula (I).

183. The method of any one of claims 164 to 182, wherein the subject exhibits a reduction in at least one symptom selected from the group consisting of conjunctival redness, conjunctival edema, conjunctival congestion, eyelid redness, eyelid edema, eyelid congestion, itchy eyes, visible corneal damage, mucous eye discharge, watery eye discharge, tearing, photophobia, foreign body sensation, and difficulty opening the eyes after administration of at least one dose of the variant of the artificial polypeptide of formula (I).

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

185. 1. A method for treating or preventing allergic conjunctivitis in a subject in need thereof, comprising administering an effective amount of an artificial polypeptide of formula (II) X-Y (II) to said subject a variant of X is a moiety comprising a sequence having at least 80% identity with 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 having at most 90% identity to SEQ ID NO:2, said mutants being characterized in that they have at least 1, 2, 3, 4, 5, 6, 7, 8 or 9 Ds in X that are mutated to S, and / or at least 1, 2, 3, 4, 5 or 6 Es in X that are mutated to T, method.

186. 186. The method of claim 185, wherein at least 20% of the amino acids of X are selected from R, K, N, D, Q, E and H; at least 30% of the amino acids of X are selected from R, K, N, D, Q, E and H; at most 90% of the amino acids of X are selected from R, K, N, D, Q, E and H; and / or at most 80% of the amino acids of X are selected from R, K, N, D, Q, E and H.

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

1.

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

2.

189. 189. The method of 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, is 5 or less.

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

191. 191. The method of any one of claims 185 to 190, 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 phlyctenular keratoconjunctivitis.

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

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

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

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

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

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

198. The method of claim 197, 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 a protruding scleral buckle, and elevated corneal scars.

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

200. 192. The method of claim 191, wherein the phlyctenular keratoconjunctivitis is caused or partially caused by delayed hypersensitivity or inflammatory reactions 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 the group consisting of bacteria (e.g., Staphylococcus aureus, Streptococcus viridians, Mycobacterium tuberculosis), viruses (e.g., herpes simplex virus), chlamydia, fungi (e.g., Candida, e.g., Candida albicans), and parasites (e.g., tapeworms, e.g., Hymenolepis nana; and nematodes).

202. 202. The method of any one of claims 185 to 201, 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 a dry eye-related disorder.

203. The method of any one of claims 185 to 202, wherein the subject experiences at least one symptom selected from the group consisting of conjunctival redness, conjunctival edema, conjunctival congestion, eyelid redness, eyelid edema, eyelid congestion, itchy eyes, visible corneal damage, mucous eye discharge, watery eye discharge, tearing, photophobia, foreign body sensation, and difficulty opening the eyes prior to administration of the variant of the artificial polypeptide of formula (II).

204. The method of any one of claims 185 to 203, wherein the subject exhibits a reduction in at least one symptom selected from the group consisting of conjunctival redness, conjunctival edema, conjunctival congestion, eyelid redness, eyelid edema, eyelid congestion, ocular itching, visible corneal damage, mucous eye discharge, watery eye discharge, tearing, photophobia, foreign body sensation, and difficulty opening the eyes after administration of at least one dose of the variant of the artificial polypeptide of formula (II).

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

206. A method for treating or preventing allergic conjunctivitis in a subject in need thereof, comprising administering an effective amount of an artificial polypeptide of formula (III): X-Y(III) to said subject a variant of X is a moiety comprising 40-65 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 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; said mutants being characterized in that they have at least 1, 2, 3, 4, 5, 6, 7, 8 or 9 Ds in X that are mutated to S, and / or at least 1, 2, 3, 4, 5 or 6 Es in X that are mutated to T, method.

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

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

1.

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

2.

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

211. 211. The method of 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, or 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. 212. The method of 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 15 or less, and / or the total number of hydrophobic amino acids in X is 10 or less.

213. 213. The method of any one of claims 206 to 212, 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 phlyctenular keratoconjunctivitis.

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

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

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

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

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

219. 214. The method of claim 213, wherein the giant papillary conjunctivitis is caused or 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 a protruding scleral buckle, and elevated corneal scars.

221. 214. 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 phlyctenular keratoconjunctivitis is caused or partially caused by delayed-type 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 the group consisting of bacteria (e.g., Staphylococcus aureus, Streptococcus viridians, Mycobacterium tuberculosis), viruses (e.g., herpes simplex virus), chlamydia, fungi (e.g., Candida, e.g., Candida albicans), and parasites (e.g., tapeworms, e.g., Hymenolepis nana; and nematodes).

224. 224. The method of any one of claims 206 to 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 disorders.

225. The method of any one of claims 206 to 224, wherein the subject experiences at least one symptom selected from the group consisting of conjunctival redness, conjunctival edema, conjunctival congestion, eyelid redness, eyelid edema, eyelid congestion, itchy eyes, visible corneal damage, mucous eye discharge, watery eye discharge, tearing, photophobia, foreign body sensation, and difficulty opening the eyes prior to administration of the variant of the artificial polypeptide of formula (III).

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

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

228. A method for treating or preventing allergic conjunctivitis in a subject in need thereof, comprising administering an effective amount of an artificial polypeptide of formula (IV): X-Y(IV) to said subject a variant of X is a moiety comprising 40-65 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 having at least 80% identity with SEQ ID NO: 2; X comprises a sequence having at most 90% identity to SEQ ID NO: 1; said mutants being characterized in that they have at least 1, 2, 3, 4, 5, 6, 7, 8 or 9 Ds in X that are mutated to S, and / or at least 1, 2, 3, 4, 5 or 6 Es in X that are mutated to T, method.

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

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

1.

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

2.

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

233. 233. The method of any one of claims 228 to 232, wherein the total number of hydrophilic amino acids in X is greater than 10, wherein the total number of hydrophilic amino acids in X is greater than 15, wherein the total number of hydrophilic amino acids in X is greater than 20, wherein the total number of hydrophilic amino acids in X is greater than 25, wherein the total number of hydrophobic amino acids in X is 15 or less, and / or wherein the total number of hydrophobic amino acids in X is 10 or less.

234. 234. The method of any one of claims 228 to 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 phlyctenular keratoconjunctivitis.

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

236. 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. 235. The method of claim 234, wherein the perennial allergic conjunctivitis is caused or 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 house dust mites, cockroaches, and animal dander.

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

240. 235. The method of claim 234, wherein the giant papillary conjunctivitis is caused or 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 a protruding scleral buckle, and elevated corneal scars.

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 phlyctenular keratoconjunctivitis is caused or partially caused by a delayed-type hypersensitivity 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 viridians, Mycobacterium tuberculosis), viruses (e.g., herpes simplex virus), chlamydia, fungi (e.g., Candida, e.g., Candida albicans), and parasites (e.g., tapeworms, e.g., Hymenolepis nana; and nematodes).

245. 245. The method of any one of claims 228 to 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 a dry eye-related disorder.

246. The method of any one of claims 228 to 245, wherein the subject experiences at least one symptom selected from the group consisting of conjunctival redness, conjunctival edema, conjunctival congestion, eyelid redness, eyelid edema, eyelid congestion, itchy eyes, visible corneal damage, mucous eye discharge, watery eye discharge, tearing, photophobia, foreign body sensation, and difficulty opening the eyes prior to administration of the variant of the artificial polypeptide of formula (IV).

247. The method of any one of claims 228 to 246, wherein the subject exhibits a reduction in at least one symptom selected from the group consisting of conjunctival redness, conjunctival edema, conjunctival congestion, eyelid redness, eyelid edema, eyelid congestion, itchy eyes, visible corneal damage, mucous eye discharge, watery eye discharge, tearing, photophobia, foreign body sensation, and difficulty opening the eyes after administration of at least one dose of the variant of the artificial polypeptide of formula (IV).

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

249. A method for treating or preventing allergic conjunctivitis in a subject in need thereof, comprising administering an effective amount of an artificial polypeptide of formula (V): X-Y (V) to said subject a variant of X is a moiety comprising a sequence having at least 80% identity with SEQ ID NO: 1; Y is a moiety comprising 10 to 30 amino acids, and Y comprises a sequence having at least 10 consecutive AA of SEQ ID NO:2; said mutants being characterized in that they have at least 1, 2, 3, 4, 5, 6, 7, 8 or 9 Ds in X that are mutated to S, and / or at least 1, 2, 3, 4, 5 or 6 Es in X that are mutated to T, method.

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

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

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

1.

253. 253. The method of any one of claims 249 to 252, wherein Y comprises a sequence having at most 80% identity to SEQ ID NO:2, or wherein Y comprises a sequence having at most 70% identity to SEQ ID NO:2, or wherein Y comprises a sequence having at most 50% identity 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 the group consisting of seasonal allergic conjunctivitis, perennial allergic conjunctivitis, vernal keratoconjunctivitis, giant papillary conjunctivitis, atopic keratoconjunctivitis, and phlyctenular keratoconjunctivitis.

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

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

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

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

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

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

261. The method of claim 260, 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 a protruding scleral buckle, and elevated corneal scars.

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 phlyctenular keratoconjunctivitis is caused or partially caused by a delayed-type hypersensitivity or 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 the group consisting of bacteria (e.g., Staphylococcus aureus, Streptococcus viridians, Mycobacterium tuberculosis), viruses (e.g., herpes simplex virus), chlamydia, fungi (e.g., Candida, e.g., Candida albicans), and parasites (e.g., tapeworms, e.g., Hymenolepis nana; and nematodes).

265. 265. The method of any one of claims 249 to 264, 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 a dry eye-related disorder.

266. The method of any one of claims 249 to 265, wherein the subject experiences at least one symptom selected from the group consisting of conjunctival redness, conjunctival edema, conjunctival congestion, eyelid redness, eyelid edema, eyelid congestion, itchy eyes, visible corneal damage, mucous eye discharge, watery eye discharge, tearing, photophobia, foreign body sensation, and difficulty opening the eyes prior to administration of the variant of the artificial polypeptide of formula (V).

267. The method of any one of claims 249 to 266, wherein the subject exhibits a reduction in at least one symptom selected from the group consisting of conjunctival redness, conjunctival edema, conjunctival congestion, eyelid redness, eyelid edema, eyelid congestion, ocular itching, visible corneal damage, mucous eye discharge, watery eye discharge, tearing, photophobia, foreign body sensation, and difficulty opening the eyes after administration of at least one dose of the variant of the artificial polypeptide of formula (V).

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

269. 1. 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 SEQ ID NO: 28, SEQ ID NO: 57, and 62-74, or a fragment or variant thereof.

270. 269. The method of claim 269, wherein the polypeptide is a polypeptide of any one of SEQ ID NOs: 28, 57, and 62-74, or a fragment or variant thereof; wherein the polypeptide is a polypeptide of any one of SEQ ID NOs: 28, 57, and 62-74; wherein the polypeptide is a polypeptide of any one of SEQ ID NOs: 28, and 62-74; or wherein 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 the group consisting of seasonal allergic conjunctivitis, perennial allergic conjunctivitis, vernal keratoconjunctivitis, giant papillary conjunctivitis, atopic keratoconjunctivitis, and phlyctenular keratoconjunctivitis.

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

273. 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. 272. The method of claim 271, wherein the perennial allergic conjunctivitis is caused 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 house 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 palpebral vernal keratoconjunctivitis, limbal vernal keratoconjunctivitis, and mixed vernal keratoconjunctivitis.

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

278. The method of claim 277, 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 a protruding scleral buckle, and elevated corneal scars.

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 phlyctenular keratoconjunctivitis is caused or partially caused by delayed hypersensitivity or inflammatory reactions 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 viridians, Mycobacterium tuberculosis), viruses (e.g., herpes simplex virus), chlamydia, fungi (e.g., Candida, e.g., Candida albicans), and parasites (e.g., tapeworms, e.g., Hymenolepis nana; and nematodes).

282. 282. The method of any one of claims 269 to 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 to 282, wherein the subject experiences at least one symptom selected from the group consisting of conjunctival redness, conjunctival edema, conjunctival congestion, eyelid redness, eyelid edema, eyelid congestion, itchy eyes, visible corneal damage, mucous eye discharge, watery eye discharge, tearing, photophobia, foreign body sensation, and difficulty opening the eyes prior to administration of the polypeptide having at least 70% identity to any one of SEQ ID NOs: 28, 57, and 62-74, or a fragment or variant thereof.

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

285. The method of any one of claims 269 to 284, wherein the subject exhibits 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 having at least 70% identity to any one selected from SEQ ID NO: 28, SEQ ID NO: 57 and 62-74, or a fragment or variant thereof.

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