METHODS FOR TREATING ACNE
The present disclosure relates to methods and materials for treating acne in a subject including, for example, moderate and/or severe acne, using anti-IL-1β binding molecules such as an anti-IL-1β antibody or binding fragment thereof.
1 . A method of treating acne in a subject, the method comprising: administering to the subject an amount of an anti-IL-1β antibody or binding fragment thereof.
2 . The method of claim 1 , wherein the acne is not responsive to conventional therapy.
3 . The method of claim 1 , wherein the acne is not responsive to treatment with one or more anti-microbial agents.
4 . The method of claim 1 further comprising selecting a subject with acne that is not responsive to treatment with one or more anti-microbial agents.
5 . The method of claim 3 or 4 , wherein the anti-microbial agent is an antibiotic.
6 . The method of claim 5 , wherein the antibiotic is an oral antibiotic.
7 . The method of any one of claims 1 - 4 , wherein the acne is acne vulgaris.
8 . The method of claim 7 , wherein the acne is moderate, severe, or moderate to severe acne vulgaris.
9 . The method of any one of claims 1 - 4 , wherein the acne is nodular acne or cystic acne.
10 . The method of any one of claims 1 - 4 , wherein the acne is nodulocystic acne.
11 . The method of any one of claims 1 - 4 , wherein the acne is severe nodulocystic acne or severe recalcitrant nodulocystic acne.
12 . The method of any one of claims 1 - 11 , wherein the method of treating results in a reduction in total lesion count.
13 . The method of any one of claims 1 - 11 , wherein the method of treating results in a reduction in number of facial and/or non-facial acne lesions in the subject.
14 . The method of any one of claims 1 - 11 , wherein the method of treating results in a reduction in severity of acne lesions in the subject.
15 . The method of any one of claims 12 - 14 , wherein the acne lesions include lesions that are inflammatory lesions.
16 . The method of claim 15 , wherein the inflammatory lesions include lesions that are facial lesions.
17 . The method of claim 15 , wherein the inflammatory lesions include lesions that are paples, pustules, or nodules.
18 . The method of any one of claims 12 - 14 , wherein the acne lesions include lesions that are non-inflammatory lesions.
19 . The method of claim 18 , wherein the non-inflammatory acne lesions include lesions that are facial lesions.
20 . The method of claim 18 , wherein the non-inflammatory acne lesions include lesions that are open or closed comedones.
21 . The method of claim 12 , wherein the reduction in number of acne lesions is a reduction in facial acne lesion count.
22 . The method of any one of claims 1 - 21 , wherein the method of treating results in an improvement in Investigator's Global Assessment (IGA) severity grade for facial acne.
23 . The method of any one of claims 1 - 21 , wherein the method of treating results in an improvement in Investigator's Global Assessment (IGA) severity grade for non-facial acne.
24 . The method of any one of claims 1 - 23 , wherein the method of treating results in an improvement in a quality of life assessment.
25 . The method of claim 24 , wherein the method of treating results in an improvement in a Cardiff Acne Disability Index (CADI) score.
26 . The method of any one of claims 1 - 25 , wherein the method of treating results in a reduction of sebum production, a reduction in hyperkeratinization, a reduction in colonization by P. acnes , or a reduction in release of inflammatory mediators into the skin.
27 . The method of any one of claims 1 - 25 , wherein the method of treating is effective to reduce one or more symptoms of skin inflammation selected from the group consisting of: redness, swelling, leukocyte infiltration, and lesion development.
28 . The method of any one of claims 1 - 25 , wherein the method of treating is effective to improve one or more acne parameters selected from the group consisting of: scaling, erythema, itching, burning, and stinging.
29 . The method of any one of claims 1 - 25 , wherein the method of treating results in a reduction in size of acne lesions, redness of acne lesions, and/or itchiness of acne lesions.
30 . The method of any one of claims 1 - 25 , wherein the method of treating results in a delay in the recurrence of an acute acne outbreak in the subject.
31 . The method of any one of claims 1 - 25 , wherein the method of treating results in a reduction in the severity of a recurrence of an acute acne outbreak in the subject.
32 . The method of any one of claims 5 - 31 , wherein the antibiotic is selected from the group consisting of: a penicillin, a polyketide antibiotic, a cephalosporin, a lincosamide, a quinolone, a folic acid synthesis inhibitor, a tetracycline, a rifamycin, a sulfonamide, an aminoglycoside, fusidic acid, a polypeptide antibiotic, a lipopeptide antibiotic, chloramphenicol and mupirocin.
33 . The method of claim 32 , wherein the antibiotic is an oral antibiotic.
34 . The method of claim 32 , wherein the antibiotic is a topical antibiotic.
35 . The method of claim 32 , wherein the penicillin is penicillin, amoxicillin, benzylpenicillin, ampicillin, or augmentin
36 . The method of claim 32 , wherein the polyketide antibiotic is macrolide, azithromycin, erythromycin, or clarithromycin.
37 . The method of claim 32 , wherein the cephalosporin is cefadroxil, cefixime, or cephalexin.
38 . The method of claim 32 , wherein the lincosamide is clindamycin.
39 . The method of claim 32 , wherein the quinolone is ciprofloxacin, levofloxacin, or moxifloxacin.
40 . The method of claim 32 , wherein the folic acid synthesis inhibitor is a dihydrofolate reductase inhibitor, trimethoprim, dapsone, or co-trimoxazole.
41 . The method of claim 32 , wherein the tetracycline is tetracycline, minocycline, doxycycline, demeclocycline, or oxytetracycline.
42 . The method of claim 32 , wherein the rifamycin is rifampicin, rifabutin, or rifapentine.
43 . The method of claim 32 , wherein the sulfonamide is sulfamethoxazole, or sulfacetamide.
44 . The method of claim 32 , wherein the aminoglycoside is neomycin, amikacin, or tobramycin.
45 . The method of claim 32 , wherein the polypeptide antibiotic is bacitracin, or polymixin B.
46 . The method of claim 32 , wherein the lipopeptide antibiotic is daptomycin.
47 . The method of any one of claims 1 - 4 , wherein the acne is associated with P. acnes or S. aureus.
48 . The method of any one of claims 1 - 47 , wherein the antibody or binding fragment thereof binds to human IL-1β with a dissociation constant of about 1 nM or less, about 250 pM or less, about 50 pM or less, about 10 pM or less, about 1 pM or less, or about 0.3 pM or less.
49 . The method of any one of claims 1 - 47 , wherein the anti-IL-1β antibody or binding fragment thereof is a neutralizing antibody.
50 . The method of any one of claims 1 - 47 , wherein the anti-IL-1β antibody or binding fragment thereof binds to an IL-1β epitope such that the bound antibody or fragment substantially permits the binding of IL-1β to IL-1 receptor I (IL-IRI).
51 . The method of any one of claims 1 - 47 , wherein the anti-IL-1β antibody or binding fragment thereof binds IL-1β and is not cross-reactive with IL-1a and/or IL-1Ra.
52 . The method of any one of claims 1 - 47 , wherein the antibody or binding fragment thereof does not detectably bind to IL-1a, IL-1 R or IL-1 Ra.
53 . The method of any one of claims 1 - 47 , wherein the anti-IL-1β antibody or binding fragment thereof comprises a heavy chain variable region comprising: a heavy chain complementarity determining region 1 (HCDR1) comprising TSGMGVG (SEQ ID NO: 13), a heavy chain complementarity determining region 2 (HCDR2) comprising HIWWDGDESYNPSLK (SEQ ID NO: 14), and/or a heavy chain complementarity determining region 3 (HCDR3) comprising NRYDPPWFVD (SEQ ID NO: 15); and/or a light chain variable region comprising: a light chain complementarity determining region 1 (LCDR1) comprising RASQDISNYLS (SEQ ID NO: 16), a light chain complementarity determining region 2 (LCDR2) comprising YTSKLHS (SEQ ID NO: 17), and/or a light chain complementarity determining region 3 (LCDR3) comprising LQGKMLPWT (SEQ ID NO: 18).
54 . The method of any one of claims 1 - 47 , wherein the antibody or binding fragment thereof comprises the light chain variable region of SEQ ID NO: 5 and the heavy chain variable region of SEQ ID NO: 6.
55 . The method of any one of claims 1 - 47 , wherein the antibody or binding fragment thereof competes with the binding of an antibody having the light chain variable region of SEQ ID NO: 5 and the heavy chain variable region of SEQ ID NO: 6.
56 . The method of any one of claims 1 - 47 , wherein the antibody or binding fragment thereof binds to an epitope of IL-1β that is substantially the same as the epitope bound by an antibody having the light chain variable region of SEQ ID NO: 5 and the heavy chain variable region of SEQ ID NO: 6.
57 . The method of any one of claims 1 - 47 , wherein the antibody or binding fragment thereof binds to an epitope contained in the amino acid sequence ESVDPKNYPKKKMEKRFVFNKIE (SEQ ID NO: 1) which corresponds to residues 83-105 of human IL-1β (SEQ ID NO: 35).
58 . The method of any one of claims 1 - 47 , wherein the antibody or binding fragment thereof binds to an epitope of human IL-1β that comprises:
(a) a valine residue at a position corresponding to position 72 (Val72) of the human IL-1β sequence set forth in SEQ ID NO: 35,
(b) a leucine residue at position 73 (Leu73) of the human IL-1β sequence set forth in SEQ ID NO: 35,
(c) a lysine residue at a position corresponding to position 74 (Lys74) of the human IL-1β sequence set forth in SEQ ID NO: 35,
(d) an aspartic acid residue at a position corresponding to position 75 (Asp75) of the human IL-1β sequence set forth in SEQ ID NO: 35,
(e) a glutamine residue at a position corresponding to position 81 (Gln81) of the human IL-1β sequence set forth in SEQ ID NO: 35,
(f) a glutamic acid residue at a position corresponding to position 83 (Glu83) of the human IL-1β sequence set forth in SEQ ID NO: 35,
(g) a serine residue at a position corresponding to position 84 (Ser84) of the human IL-1β sequence set forth in SEQ ID NO: 35,
(h) an asparagine residue at a position corresponding to position 89 (Asn89) of the human IL-1β sequence set forth in SEQ ID NO: 35,
(i) a tyrosine residue at a position corresponding to position 90 (Tyr90) of the human IL-1β sequence set forth in SEQ ID NO: 35,
(j) a lysine residue at a position corresponding to position 92 (Lys92) of the human IL-1β sequence set forth in SEQ ID NO: 35,
(k) a lysine residue at a position corresponding to position 94 (Lys94) of the human IL-1β sequence set forth in SEQ ID NO: 35,
(l) a glutamic acid residue at a position corresponding to position 96 (Glu96) of the human IL-1β sequence set forth in SEQ ID NO: 35,
(m) a lysine residue at a position corresponding to position 97 (Lys97) of the human IL-1β sequence set forth in SEQ ID NO: 35,
(n) an arginine residue at a position corresponding to position 98 (Arg98) of the human IL-1β sequence set forth in SEQ ID NO: 35,
(o) an alanine residue at a position corresponding to position 115 (Ala115) of the human IL-1β sequence set forth in SEQ ID NO: 35,
(p) a glutamine residue at a position corresponding to position 116 (Gln116) of the human IL-1β sequence set forth in SEQ ID NO: 35, and/or
(q) a phenylalanine residue at a position corresponding to position 117 (Phe117) of the human IL-16 sequence set forth in SEQ ID NO: 35.
59 . The method of any one of claims 1 - 47 , wherein the antibody or binding fragment thereof is human or humanized.
60 . The method of any one of claims 1 - 59 , wherein the anti-IL-1β antibody or binding fragment thereof is administered by subcutaneous, intravenous, intradermal or intramuscular injection.
61 . The method of any one of claims 1 - 59 , wherein the anti-IL-1β antibody or binding fragment thereof is administered in a dose of 1 mg/kg or less or a dose less than or equal to 1 mg/kg
62 . The method of any one of claims 1 - 59 , wherein the anti-IL-1β antibody or binding fragment thereof is administered in a dose of 0.2 mg/kg or 0.6 mg/kg
63 . The method of any one of claims 1 - 59 , wherein the anti-IL-1β antibody or binding fragment thereof is administered in a dose of less than 100 mg.
64 . The method of any one of claims 1 - 59 , wherein the anti-IL-1β antibody or binding fragment thereof is administered monthly, every two months, every three months, every four months, every five months, or every six months.
65 . A method of treating acne in a subject, the method comprising: administering to the subject an amount of an anti-IL-1β antibody or binding fragment thereof, wherein the acne is not responsive to conventional therapy.
66 . A method of treating acne in a subject, the method comprising: administering to the subject an amount of an anti-IL-1β antibody or binding fragment thereof, wherein the acne is not responsive to treatment with one or more anti-microbial agents.
67 . The method of claim 65 or 66 further comprising selecting a subject with acne that is not responsive to treatment with one or more anti-microbial agents.
68 . The method of claim 66 or 67 , wherein the anti-microbial agent is an antibiotic.
69 . The method of claim 68 , wherein the antibiotic is an oral antibiotic.
70 . The method of any one of claims 65 - 67 , wherein the acne is acne vulgaris.
71 . The method of claim 70 , wherein the acne is moderate, severe, or moderate to severe acne vulgaris.
72 . The method of any one of claims 65 - 67 , wherein the acne is nodular acne or cystic acne.
73 . The method of any one of claims 65 - 67 , wherein the acne is nodulocystic acne.
74 . The method of any one of claims 65 - 67 , wherein the acne is severe nodulocystic acne or severe recalcitrant nodulocystic acne.
75 . The method of any one of claims 65 - 74 , wherein the method of treating results in a reduction in total lesion count.
76 . The method of any one of claims 65 - 74 , wherein the method of treating results in a reduction in number of facial and/or non-facial acne lesions in the subject.
77 . The method of any one of claims 65 - 74 , wherein the method of treating results in a reduction in severity of acne lesions in the subject.
78 . The method of any one of claims 75 - 77 , wherein the acne lesions include lesions that are inflammatory lesions.
79 . The method of claim 78 , wherein the inflammatory lesions include lesions that are facial lesions.
80 . The method of claim 78 , wherein the inflammatory lesions include lesions that are paples, pustules, or nodules.
81 . The method of any one of claims 75 - 77 , wherein the acne lesions include lesions that are non-inflammatory lesions.
82 . The method of claim 81 , wherein the non-inflammatory acne lesions include lesions that are facial lesions.
83 . The method of claim 81 , wherein the non-inflammatory acne lesions include lesions that are open or closed comedones.
84 . The method of claim 75 , wherein the reduction in number of acne lesions is a reduction in facial acne lesion count.
85 . The method of any one of claims 65 - 84 , wherein the method of treating results in an improvement in Investigator's Global Assessment (IGA) severity grade for facial acne.
86 . The method of any one of claims 65 - 84 , wherein the method of treating results in an improvement in Investigator's Global Assessment (IGA) severity grade for non-facial acne.
87 . The method of any one of claims 65 - 84 , wherein the method of treating results in an improvement in a quality of life assessment.
88 . The method of claim 87 , wherein the method of treating results in an improvement in a Cardiff Acne Disability Index (CADI) score.
89 . The method of any one of claims 65 - 88 , wherein the method of treating results in a reduction of sebum production, a reduction in hyperkeratinization, a reduction in colonization by P. acnes , or a reduction in release of inflammatory mediators into the skin.
90 . The method of any one of claims 65 - 88 , wherein the method of treating is effective to reduce one or more symptoms of skin inflammation selected from the group consisting of: redness, swelling, leukocyte infiltration, and lesion development.
91 . The method of any one of claims 65 - 88 , wherein the method of treating is effective to improve one or more acne parameters selected from the group consisting of: scaling, erythema, itching, burning, and stinging.
92 . The method of any one of claims 65 - 88 , wherein the method of treating results in a reduction in size of acne lesions, redness of acne lesions, and/or itchiness of acne lesions.
93 . The method of any one of claims 65 - 88 , wherein the method of treating results in a delay in the recurrence of an acute acne outbreak in the subject.
94 . The method of any one of claims 65 - 88 , wherein the method of treating results in a reduction in the severity of a recurrence of an acute acne outbreak in the subject.
95 . The method of any one of claims 68 - 94 , wherein the antibiotic is selected from the group consisting of: a penicillin, a polyketide antibiotic, a cephalosporin, a lincosamide, a quinolone, a folic acid synthesis inhibitor, a tetracycline, a rifamycin, a sulfonamide, an aminoglycoside, fusidic acid, a polypeptide antibiotic, a lipopeptide antibiotic, chloramphenicol and mupirocin.
96 . The method of claim 95 , wherein the antibiotic is an oral antibiotic.
97 . The method of claim 95 , wherein the antibiotic is a topical antibiotic.
98 . The method of claim 95 , wherein the penicillin is penicillin, amoxicillin, benzylpenicillin, ampicillin, or augmentin
99 . The method of claim 95 , wherein the polyketide antibiotic is macrolide, azithromycin, erythromycin, or clarithromycin.
100 . The method of claim 95 , wherein the cephalosporin is cefadroxil, cefixime, or cephalexin.
101 . The method of claim 95 , wherein the lincosamide is clindamycin.
102 . The method of claim 95 , wherein the quinolone is ciprofloxacin, levofloxacin, or moxifloxacin.
103 . The method of claim 95 , wherein the folic acid synthesis inhibitor is a dihydrofolate reductase inhibitor, trimethoprim, dapsone, or co-trimoxazole.
104 . The method of claim 95 , wherein the tetracycline is tetracycline, minocycline, doxycycline, demeclocycline, or oxytetracycline.
105 . The method of claim 95 , wherein the rifamycin is rifampicin, rifabutin, or rifapentine.
106 . The method of claim 95 , wherein the sulfonamide is sulfamethoxazole, or sulfacetamide.
107 . The method of claim 95 , wherein the aminoglycoside is neomycin, amikacin, or tobramycin.
108 . The method of claim 95 , wherein the polypeptide antibiotic is bacitracin, or polymixin B.
109 . The method of claim 95 , wherein the lipopeptide antibiotic is daptomycin.
110 . The method of any one of claims 65 - 67 , wherein the acne is associated with P. acnes or S. aureus.
111 . The method of any one of claims 1 - 110 , wherein the antibody or binding fragment thereof binds to human IL-1β with a dissociation constant of about 1 nM or less, about 250 pM or less, about 50 pM or less, about 10 pM or less, about 1 pM or less, or about 0.3 pM or less.
112 . The method of any one of claims 1 - 110 , wherein the anti-IL-1β antibody or binding fragment thereof is a neutralizing antibody.
113 . The method of any one of claims 1 - 110 , wherein the anti-IL-1β antibody or binding fragment thereof binds to an IL-1β epitope such that the bound antibody or fragment substantially permits the binding of IL-1β to IL-1 receptor I (IL-IRI).
114 . The method of any one of claims 1 - 110 , wherein the anti-IL-1β antibody or binding fragment thereof binds IL-1β and is not cross-reactive with IL-1a and/or IL-1Ra.
115 . The method of any one of claims 1 - 110 , wherein the anti-IL-1β antibody or binding fragment thereof does not detectably bind to IL-1a, IL-1R or IL-1Ra.
116 . The method of any one of claims 1 - 110 , wherein the anti-IL-1β antibody or binding fragment thereof comprises a heavy chain variable region comprising: a complementarity determining region 1 (HCDR1) comprising TSGMGVG (SEQ ID NO: 13), a heavy chain complementarity determining region 2 (HCDR2) comprising HIWWDGDESYNPSLK (SEQ ID NO: 14), and/or a heavy chain complementarity determining region 3 (HCDR3) comprising NRYDPPWFVD (SEQ ID NO: 15); and/or a light chain variable region comprising: a complementarity determining region 1 (LCDR1) comprising RASQDISNYLS (SEQ ID NO: 16), a light chain complementarity determining region 2 (LCDR2) comprising YTSKLHS (SEQ ID NO: 17), and/or a light chain complementarity determining region 3 (LCDR3) comprising LQGKMLPWT (SEQ ID NO: 18).
117 . The method of any one of claims 1 - 110 , wherein the antibody or binding fragment thereof comprises the light chain variable region of SEQ ID NO:5 and the heavy chain variable region of SEQ ID NO:6.
118 . The method of any one of claims 1 - 110 , wherein the antibody or binding fragment thereof competes with the binding of an antibody having the light chain variable region of SEQ ID NO:5 and the heavy chain variable region of SEQ ID NO:6.
119 . The method of any one of claims 1 - 110 , wherein the antibody or binding fragment thereof binds to an epitope of IL-1β that is substantially the same as the epitope bound by an antibody having the light chain variable region of SEQ ID NO:5 and the heavy chain variable region of SEQ ID NO:6.
120 . The method of any one of claims 1 - 110 , wherein the antibody or binding fragment thereof binds to an epitope contained in the amino acid sequence ESVDPKNYPKKKMEKRFVFNKIE (SEQ ID NO: 1) which corresponds to residues 83-105 of human IL-1β (SEQ ID NO: 35)
121 . The method of any one of claims 1 - 110 , wherein the antibody or binding fragment thereof binds to an epitope of human IL-1β that comprises:
(a) a valine residue at a position corresponding to position 72 (Val72) of the human IL-1β sequence set forth in SEQ ID NO: 35,
(b) a leucine residue at position 73 (Leu73) of the human IL-1β sequence set forth in SEQ ID NO: 35,
(c) a lysine residue at a position corresponding to position 74 (Lys74) of the human IL-1β sequence set forth in SEQ ID NO: 35,
(d) an aspartic acid residue at a position corresponding to position 75 (Asp75) of the human IL-1β sequence set forth in SEQ ID NO: 35,
(e) a glutamine residue at a position corresponding to position 81 (Gln81) of the human IL-1β sequence set forth in SEQ ID NO: 35,
(f) a glutamic acid residue at a position corresponding to position 83 (Glu83) of the human IL-1β sequence set forth in SEQ ID NO: 35,
(g) a serine residue at a position corresponding to position 84 (Ser84) of the human IL-1β sequence set forth in SEQ ID NO: 35,
(h) an asparagine residue at a position corresponding to position 89 (Asn89) of the human IL-1β sequence set forth in SEQ ID NO: 35,
(i) a tyrosine residue at a position corresponding to position 90 (Tyr90) of the human IL-1β sequence set forth in SEQ ID NO: 35,
(j) a lysine residue at a position corresponding to position 92 (Lys92) of the human IL-1β sequence set forth in SEQ ID NO: 35,
(k) a lysine residue at a position corresponding to position 94 (Lys94) of the human IL-1β sequence set forth in SEQ ID NO: 35,
(l) a glutamic acid residue at a position corresponding to position 96 (Glu96) of the human IL-1β sequence set forth in SEQ ID NO: 35,
(m) a lysine residue at a position corresponding to position 97 (Lys97) of the human IL-1β sequence set forth in SEQ ID NO: 35,
(n) an arginine residue at a position corresponding to position 98 (Arg98) of the human IL-1β sequence set forth in SEQ ID NO: 35,
(o) an alanine residue at a position corresponding to position 115 (Ala115) of the human IL-1β sequence set forth in SEQ ID NO: 35,
(p) a glutamine residue at a position corresponding to position 116 (Gln116) of the human IL-1β sequence set forth in SEQ ID NO: 35, and/or
(q) a phenylalanine residue at a position corresponding to position 117 (Phe117) of the human IL-16 sequence set forth in SEQ ID NO: 35.
122 . The method of any one of claims 1 - 110 , wherein the antibody or binding fragment thereof is human or humanized.
123 . The method of any one of claims 1 - 122 , wherein the anti-IL-1β antibody or binding fragment thereof is administered by subcutaneous, intravenous, intradermal or intramuscular injection.
124 . A method of treating a subject with acne, the method comprising:
a.) scoring the acne at a first time;
b.) administering to the subject conventional therapy for treatment of the acne;
c.) scoring the acne at a second time;
d.) determining that the subject is not responsive to conventional therapy where there is not an improvement in a score assessed to the acne between the scoring at the first time and the scoring at the second time; and
e.) administering to the subject an amount of anti-IL-1β antibody or binding fragment thereof.
125 . A method of treating a subject with acne, the method comprising:
a.) scoring the acne at a first time;
b.) administering to the subject one or more anti-microbial agents for treatment of the acne;
c.) scoring the acne at a second time;
d.) determining that the subject is not responsive to treatment with the anti-microbial agent where there is not an improvement in a score assessed to the acne between the scoring at the first time and the scoring at the second time; and
e.) administering to the subject an amount of anti-IL-1β antibody or binding fragment thereof.
126 . The method of claim 124 or 125 further comprising diagnosing acne in the subject.
127 . The method of claim 125 , wherein the anti-microbial agent is an antibiotic.
128 . The method of claim 127 , wherein the antibiotic is an oral antibiotic.
129 . The method of claim 124 or 125 , wherein the acne is acne vulgaris.
130 . The method of claim 129 , wherein the acne vulgaris is moderate, severe, or moderate to severe acne vulgaris.
131 . The method of claim 124 or 125 , wherein the acne is nodular acne or cystic acne.
132 . The method of claim 124 or 125 , wherein the acne is nodulocystic acne.
133 . The method of claim 124 or 125 , wherein the acne is severe nodulocystic acne or severe recalcitrant nodulocystic acne.
134 . The method of any one of claims 124 - 133 , wherein the method of treating results in a reduction in total lesion count.
135 . The method of any one of claims 124 - 133 , wherein the method of treating results in a reduction in number of facial and/or non-facial acne lesions in the subject.
136 . The method of any one of claims 124 - 133 , wherein the method of treating results in a reduction in severity of acne lesions in the subject.
137 . The method of any one of claims 134 - 136 , wherein the acne lesions include lesions that are inflammatory lesions.
138 . The method of claim 137 , wherein the inflammatory lesions include lesions that are facial lesions.
139 . The method of claim 137 , wherein the inflammatory lesions include lesions that are paples, pustules, or nodules.
140 . The method any one of claims 134 - 136 , wherein the acne lesions include lesions that are non-inflammatory lesions.
141 . The method of claim 140 , wherein the non-inflammatory acne lesions include lesions that are facial lesions.
142 . The method of claim 140 , wherein the non-inflammatory acne lesions include lesions that are open or closed comedones.
143 . The method of claim 134 , wherein the reduction in number of acne lesions is a reduction in facial acne lesion count.
144 . The method of any one of claims 124 - 143 , wherein the method of treating results in an improvement in Investigator's Global Assessment (IGA) severity grade for facial acne.
145 . The method of any one of claims 124 - 143 , wherein the method of treating results in an improvement in Investigator's Global Assessment (IGA) severity grade for non-facial acne.
146 . The method of any one of claims 124 - 143 , wherein the method of treating results in an improvement in a quality of life assessment.
147 . The method of claim 146 , wherein the method of treating results in an improvement in a Cardiff Acne Disability Index (CADI) score.
148 . The method of any one of claims 124 - 147 , wherein the method of treating results in a reduction of sebum production, a reduction in hyperkeratinization, a reduction in colonization by P. acnes , or a reduction in release of inflammatory mediators into the skin.
149 . The method of any one of claims 124 - 147 , wherein the method of treating is effective to reduce one or more symptoms of skin inflammation selected from the group consisting of: redness, swelling, leukocyte infiltration, and lesion development.
150 . The method of any one of claims 124 - 147 , wherein the method of treating is effective to improve one or more acne parameters selected from the group consisting of: scaling, erythema, itching, burning, and stinging.
151 . The method of any one of claims 124 - 147 , wherein the method of treating results in a reduction in size of acne lesions, redness of acne lesions, and/or itchiness of acne lesions.
152 . The method of any one of claims 124 - 147 , wherein the method of treating results in a delay in the recurrence of an acute acne outbreak in the subject.
153 . The method of any one of claims 124 - 147 , wherein the method of treating results in a reduction in the severity of a recurrence of an acute acne outbreak in the subject.
154 . The method of any one of claims 124 - 147 , wherein the antibiotic is selected from the group consisting of: a penicillin, a polyketide antibiotic, a cephalosporin, a lincosamide, a quinolone, a folic acid synthesis inhibitor, a tetracycline, a rifamycin, a sulfonamide, an aminoglycoside, fusidic acid, a polypeptide antibiotic, a lipopeptide antibiotic, chloramphenicol and mupirocin.
155 . The method of claim 154 , wherein the antibiotic is an oral antibiotic.
156 . The method of claim 154 , wherein the antibiotic is a topical antibiotic.
157 . The method of any one of claims 124 - 156 , wherein the antibody or binding fragment thereof comprises the light chain variable region of SEQ ID NO: 5 and the heavy chain variable region of SEQ ID NO: 6.
158 . The method of any one of claims 124 - 156 , wherein the antibody or fragment thereof competes with the binding of an antibody having the light chain variable region of SEQ ID NO: 5 and the heavy chain variable region of SEQ ID NO: 6.
159 . The method of any one of claims 124 - 156 , wherein the antibody or fragment thereof binds to an epitope of IL-1R that is substantially the same as the epitope bound by an antibody having the light chain variable region of SEQ ID NO: 5 and the heavy chain variable region of SEQ ID NO: 6.
160 . A method for treating acne in a subject, said method comprising administering to the subject an amount of an anti-IL-1β antibody or binding fragment thereof, wherein the anti-IL-1β antibody or binding fragment thereof comprises a heavy chain variable region comprising: a complementarity determining region 1 (HCDR1) comprising TSGMGVG (SEQ ID NO: 13), a heavy chain complementarity determining region 2 (HCDR2) comprising HIWWDGDESYNPSLK (SEQ ID NO: 14), and/or a heavy chain complementarity determining region 3 (HCDR3) comprising NRYDPPWFVD (SEQ ID NO: 15); and/or a light chain variable region comprising: a complementarity determining region 1 (LCDR1) comprising RASQDISNYLS (SEQ ID NO: 16), a light chain complementarity determining region 2 (LCDR2) comprising YTSKLHS (SEQ ID NO: 17), and/or a light chain complementarity determining region 3 (LCDR3) comprising LQGKMLPWT (SEQ ID NO: 18).
161 . A method for treating acne in a subject, said method comprising administering to the subject an amount of an anti-IL-1β antibody or binding fragment thereof comprising a heavy chain variable region of SEQ ID NO: 6 and a light chain variable region of SEQ ID NO: 5.
162 . A method for treating acne in a subject, said method comprising administering to the subject an amount of an anti-IL-1β antibody or binding fragment thereof, wherein the antibody or fragment thereof competes with the binding of an antibody having the light chain variable region of SEQ ID NO: 5 and the heavy chain variable region of SEQ ID NO: 6.
163 . A method for treating acne in a subject, said method comprising administering to the subject an amount of an anti-IL-1β antibody or binding fragment thereof, wherein the antibody or fragment binds to human IL-1β, and wherein the antibody or fragment binds to the same epitope that an antibody comprising a heavy chain variable region of SEQ ID NO: 6 and a light chain variable region of SEQ ID NO: 5 binds to.
164 . The method of any one of claims 160 - 163 , wherein the acne is not responsive to conventional therapy.
165 . The method of any one of claims 160 - 163 , wherein the acne is not responsive to treatment with one or more antimicrobial agents.
166 . The method of any one of claims 160 - 163 further comprising selecting a subject with acne that is not responsive to treatment with one or more anti-microbial agents.
167 . The method of any one of claims 160 - 163 , wherein the anti-microbial agent is an antibiotic.
168 . The method of claim 167 , wherein the antibiotic is an oral antibiotic.
169 . The method of any one of claims 160 - 163 , wherein the acne is acne vulgaris.
170 . The method of claim 169 , wherein the acne is moderate, severe, or moderate to severe acne vulgaris.
171 . The method of any one of claims 160 - 163 , wherein the acne is nodular acne or cystic acne.
172 . The method of any one of claims 160 - 163 , wherein the acne is nodulocystic acne.
173 . The method of any one of claims 160 - 163 , wherein the acne is severe nodulocystic acne or severe recalcitrant nodulocystic acne.
174 . The method of any one of claims 160 - 173 , wherein the method of treating results in a reduction in total lesion count.
175 . The method of any one of claims 160 - 173 , wherein the method of treating results in a reduction in number of facial and/or non-facial acne lesions in the subject.
176 . The method of any one of claims 160 - 173 , wherein the method of treating results in a reduction in severity of acne lesions in the subject.
177 . The method of any one of claims 174 - 176 , wherein the acne lesions include lesions that are inflammatory lesions.
178 . The method of claim 177 , wherein the inflammatory lesions include lesions that are facial lesions.
179 . The method of claim 177 , wherein the inflammatory lesions include lesions that are paples, pustules, or nodules.
180 . The method of any one of claims 174 - 176 , wherein the acne lesions include lesions that are non-inflammatory lesions.
181 . The method of claim 180 , wherein the non-inflammatory acne lesions include lesions that are facial lesions.
182 . The method of claim 180 , wherein the non-inflammatory acne lesions include lesions that are open or closed comedones.
183 . The method of claim 174 , wherein the reduction in number of acne lesions is a reduction in facial acne lesion count.
184 . The method of any one of claims 160 - 183 , wherein the method of treating results in an improvement in Investigator's Global Assessment (IGA) severity grade for facial acne.
185 . The method of any one of claims 160 - 183 , wherein the method of treating results in an improvement in Investigator's Global Assessment (IGA) severity grade for non-facial acne.
186 . The method of any one of claims 160 - 183 , wherein the method of treating results in an improvement in a quality of life assessment.
187 . The method of claim 186 , wherein the method of treating results in an improvement in a Cardiff Acne Disability Index (CADI) score.
188 . The method of any one of claims 160 - 183 , wherein the method of treating results in a reduction of sebum production, a reduction in hyperkeratinization, a reduction in colonization by P. acnes , or a reduction in release of inflammatory mediators into the skin.
189 . The method of any one of claims 160 - 183 , wherein the method of treating is effective to reduce one or more symptoms of skin inflammation selected from the group consisting of: redness, swelling, leukocyte infiltration, and lesion development.
190 . The method of any one of claims 160 - 183 , wherein the method of treating is effective to improve one or more acne parameters selected from the group consisting of: scaling, erythema, itching, burning, and stinging.
191 . The method of any one of claims 160 - 183 , wherein the method of treating results in a reduction in size of acne lesions, redness of acne lesions, and/or itchiness of acne lesions.
192 . The method of any one of claims 160 - 183 , wherein the method of treating results in a delay in the recurrence of an acute acne outbreak in the subject.
193 . The method of any one of claims 160 - 183 , wherein the method of treating results in a reduction in the severity of a recurrence of an acute acne outbreak in the subject.
194 . The method of any one of claims 160 - 183 , wherein the antibiotic is selected from the group consisting of: a penicillin, a polyketide antibiotic, a cephalosporin, a lincosamide, a quinolone, a folic acid synthesis inhibitor, a tetracycline, a rifamycin, a sulfonamide, an aminoglycoside, fusidic acid, a polypeptide antibiotic, a lipopeptide antibiotic, chloramphenicol and mupirocin.
195 . The method of claim 194 , wherein the antibiotic is an oral antibiotic.
196 . The method of claim 194 , wherein the antibiotic is a topical antibiotic.
197 . The method of claim 194 , wherein the penicillin is penicillin, amoxicillin, benzylpenicillin, ampicillin, or augmentin
198 . The method of claim 194 , wherein the polyketide antibiotic is macrolide, azithromycin, erythromycin, or clarithromycin.
199 . The method of claim 194 , wherein the cephalosporin is cefadroxil, cefixime, or cephalexin.
200 . The method of claim 194 , wherein the lincosamide is clindamycin.
201 . The method of claim 194 , wherein the quinolone is ciprofloxacin, levofloxacin, or moxifloxacin.
202 . The method of claim 194 , wherein the folic acid synthesis inhibitor is a dihydrofolate reductase inhibitor, trimethoprim, dapsone, or co-trimoxazole.
203 . The method of claim 194 , wherein the tetracycline is tetracycline, minocycline, doxycycline, demeclocycline, or oxytetracycline.
204 . The method of claim 194 , wherein the rifamycin is rifampicin, rifabutin, or rifapentine.
205 . The method of claim 194 , wherein the sulfonamide is sulfamethoxazole, or sulfacetamide.
206 . The method of claim 194 , wherein the aminoglycoside is neomycin, amikacin, or tobramycin.
207 . The method of claim 194 , wherein the polypeptide antibiotic is bacitracin, or polymixin B.
208 . The method of claim 194 , wherein the lipopeptide antibiotic is daptomycin.
209 . The method of any one of claims 160 - 164 , wherein the acne is associated with P. acnes or S. aureus.
210 . The method of any one of claims 1 - 209 , wherein one or more active agents used and/or approved for the treatment of acne are administered in conjunction with the anti-IL-1β antibody or binding fragment thereof.
211 . The method of any one of claim 210 , wherein the one or more active agents are administered as a topical treatment or an oral treatment.
212 . The method of claim 210 , wherein the one or more active agents are selected from the group consisting of: benzoyl peroxide, a retinoid, isotretinoin, a corticosteroid, a hormone therapy, UV light, azelaic acid, a topical antibiotic, and an oral antibiotic.
213 . The method of claim 212 , wherein the retinoid is retinol, retinal, tretinoin, isotretinoin, adapalene, or tazarotene.
214 . The method of claim 212 , wherein the corticosteroid is prednisone.
215 . The method of claim 212 , wherein the hormone therapy is an estrogen and/or progestin, a glucocorticoid, or an antiandrogen.
216 . The method of claim 215 , wherein the estrogens and/or progestin is norethindrone acetate-ethinyl estradiol, or norgestimate-ethinyl estradiol.
217 . The method of claim 215 , wherein the glucocorticoid is prednisone.
218 . The method of claim 215 , wherein the antiandrogen is spironolactone or flutamide.
219 . The method of claim 212 , wherein the topical antibiotic is clindamycin, zithromycin, erythromycin, minocycline, or tetracycline.
220 . The method of claim 212 , wherein the oral antibiotic is tetracycline, erythromycin, azithromycin, doxycycline, minocycline, clindamycin, ampicillin, amoxicillin, cephalosporin, or trimethoprim/sulfamethoxazole.