Anti-IL-27 Antibodies and Uses Thereof
The present disclosure relates to anti-IL-27 antibodies, and antigen-binding portions thereof. The disclosure also relates to methods for treating or ameliorating one or more symptoms of a disease, such as cancer, by administering the antibodies or antigen-binding portion thereof. The disclosure also relates to methods for detecting IL-27 in, for example, a subject or a sample.
1 - 80 . (canceled)
81 . A method for producing an antibody, or an antigen binding portion thereof, comprising culturing a cell to express the antibody or antigen binding portion thereof, wherein the antibody or antigen binding portion thereof comprises:
(a) a heavy chain CDR1 comprising an amino acid sequence selected from the amino acid sequence set forth in SEQ ID NOs: 9, 31, 53, 75, 97, or 119;
(b) a heavy chain CDR2 comprising an amino acid sequence selected from the amino acid sequence set forth in SEQ ID NOs: 10, 32, 54, 76, 98, or 120;
(c) a heavy chain CDR3 comprising an amino acid sequence selected from the amino acid sequence set forth in SEQ ID NOs: 11, 33, 55, 77, 99, or 121;
(d) a light chain CDR1 comprising an amino acid sequence selected from the amino acid sequence set forth in SEQ ID NOs: 17, 39, 61, 83, 105, or 127;
(e) a light chain CDR2 comprising an amino acid sequence selected from the amino acid sequence set forth in SEQ ID NOs: 18, 40, 62, 84, 106, or 128; and
(f) a light chain CDR3 comprising an amino acid sequence selected from the amino acid sequence set forth in SEQ ID NOs: 19, 41, 63, 85, 107, or 129.
82 . The method of claim 81 , wherein the antibody is selected from the group consisting of an IgG1, an IgG2, an IgG3, an IgG4, an IgM, an IgA1 an IgA2, an IgD, and an IgE antibody.
83 . The method of claim 82 , wherein the antibody is an IgG1 antibody or an IgG4 antibody.
84 . The method of claim 81 , wherein the antibody comprises an IgG1 heavy chain constant region or an IgG4 heavy chain constant region.
85 . The method of claim 81 , wherein the antibody comprises an Fc domain comprising at least one mutation.
86 . The method of claim 85 , wherein the antibody comprises an IgG4 heavy chain comprising a substitution selected from the group consisting of S228P, L235E, L235A, and any combination thereof, according to EU numbering.
87 . The method of claim 81 , wherein the antibody or antigen binding portion thereof comprises a variable heavy chain comprising an amino acid sequence selected from the amino acid sequence set forth in SEQ ID NOs: 15, 37, 59, 81, 103, and 125.
88 . The method of claim 81 , wherein the antibody or antigen binding portion thereof comprises a variable light chain comprising an amino acid sequence selected from the amino acid sequence set forth in SEQ ID NOs: 23, 45, 67, 89, 111, and 133.
89 . The method of claim 81 , wherein the cell is a mammalian cell.
90 . The method of claim 81 , wherein the cell is a yeast cell.
91 . The method of claim 81 , further comprising purifying the antibody or antigen binding portion thereof.
92 . The method of claim 91 , wherein the purifying comprises using a chromatographic technique selected from ion-exchange chromatography, hydrophobic chromatography, affinity chromatography, reverse-phase HPLC chromatography, or a combination thereof.
93 . The method of claim 91 , wherein the purifying comprises using an immunological technique.
94 . The method of claim 91 , wherein the purifying comprises using a protein-A chromatography column.
95 . The method of claim 81 , further comprising conjugating a therapeutic agent to the antibody or antigen binding portion thereof.
96 . The method of claim 81 , wherein the antibody or antigen binding portion thereof is glycosylated.
97 . The method of claim 81 , further comprising PEGylating the antibody or antigen binding portion thereof.
98 . A method for producing an antibody, or an antigen binding portion thereof, comprising culturing a cell to express the antibody or antigen binding portion thereof,
wherein the antibody or antigen binding portion thereof comprises heavy and light chain CDRs, wherein:
(a) the light chain CDR1 consists of N-XXXXXXLFSSNXKXYXX-C;
(b) the light chain CDR2 consists of the sequence set forth in SEQ ID NO: 131;
(c) the light chain CDR3 consists of N-XXXASAXXX-C;
(d) the heavy chain CDR1 consists of the sequence set forth in SEQ ID NO: 122;
(e) the heavy chain CDR2 consists of N-XXSSSXSYXYXXXXXXX-C; and
(f) the heavy chain CDR3 consists of N-XXXXGRTSYTATXHNXXXX-C;
wherein X is any amino acid.
99 . The method of claim 98 , wherein the antibody is selected from the group consisting of an IgG1, an IgG2, an IgG3, an IgG4, an IgM, an IgA1 an IgA2, an IgD, and an IgE antibody.
100 . The method of claim 99 , wherein the antibody is an IgG1 antibody or an IgG4 antibody.
101 . The method of claim 98 , wherein the antibody comprises an IgG1 heavy chain constant region or an IgG4 heavy chain constant region.
102 . The method of claim 98 , wherein the antibody comprises an Fc domain comprising at least one mutation.
103 . The method of claim 102 , wherein the antibody comprises an IgG4 heavy chain comprising a substitution selected from the group consisting of S228P, L235E, L235A, and any combination thereof, according to EU numbering.
104 . The method of claim 98 , wherein the cell is a mammalian cell.
105 . The method of claim 98 , wherein the cell is a yeast cell.
106 . The method of claim 98 , further comprising purifying the antibody or antigen binding portion thereof.
107 . The method of claim 106 , wherein the purifying comprises using a chromatographic technique selected from ion-exchange chromatography, hydrophobic chromatography, affinity chromatography, reverse-phase HPLC chromatography, or a combination thereof.
108 . The method of claim 106 , wherein the purifying comprises using an immunological technique.
109 . The method of claim 106 , wherein the purifying comprises using a protein-A chromatography column.
110 . The method of claim 98 , further comprising conjugating a therapeutic agent to the antibody or antigen binding portion thereof.
111 . The method of claim 98 , wherein the antibody or antigen binding portion thereof is glycosylated.
112 . The method of claim 98 , further comprising PEGylating the antibody or antigen binding portion thereof.