ANTIBODIES COMPRISING AN ANTIGEN-BINDING DOMAIN WHOSE ANTIGEN-BINDING ACTIVITY CHANGES ACCORDING TO THE ION CONCENTRATION CONDITION, Fc REGION VARIANTS, OR IL-8-BINDING ANTIBODIES

• US 20180258163A1
• Filed: 05/10/2018
• Published: 09/13/2018
• Est. Priority Date: 02/05/2015
• Status: Active Grant

• Current Assignee: Chugai Seiyaku Kabushiki Kaisha (Roche Holding AG)
• Original Assignee: Chugai Seiyaku Kabushiki Kaisha (Roche Holding AG)
• Inventors: IGAWA, Tomoyuki, MAEDA, Atsuhiko, HARAYA, Kenta, TACHIBANA, Tatsuhiko, IWAYANAGI, Yuki, HORI, Yuji, NAKAMURA, Genki, MURAOKA, Masaru
• Granted Patent: US 10,519,229 B2
• Time in Patent Office: Days
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61P 1/02 Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 11/14 Antitussive agents
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 17/12 Keratolytics, e.g. wart or anti-corn preparations
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/14 for RNA viruses
• CPC Class Codes: A61P 31/20 for DNA viruses
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 37/08 : Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 : for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C07K 16/18 : against material from animals or humans
• CPC Class Codes: C07K 16/244 : Interleukins [IL]
• CPC Class Codes: C07K 16/2866 : against receptors for cytokines, lymphokines, interferons
• CPC Class Codes: C07K 16/36 : against blood coagulation factors
• CPC Class Codes: C07K 16/40 : against enzymes
• CPC Class Codes: C07K 16/4291 : against IgE
• CPC Class Codes: C07K 2317/14 : Specific host cells or culture conditions, e.g. components, pH or temperature
• CPC Class Codes: C07K 2317/24 : containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/31 : multispecific
• CPC Class Codes: C07K 2317/51 : Complete heavy chain or Fd fragment, i.e. VH + CH1
• CPC Class Codes: C07K 2317/515 : Complete light chain, i.e. VL + CL
• CPC Class Codes: C07K 2317/52 : Constant or Fc region; Isotype
• CPC Class Codes: C07K 2317/55 : Fab or Fab'
• CPC Class Codes: C07K 2317/56 : variable (Fv) region, i.e. VH and/or VL
• CPC Class Codes: C07K 2317/76 : Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: C07K 2317/77 : Internalization into the cell
• CPC Class Codes: C07K 2317/90 : characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
• CPC Class Codes: C07K 2317/92 : Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
• CPC Class Codes: C07K 2317/94 : Stability, e.g. half-life, pH, temperature or enzyme-resistance
• CPC Class Codes: G01N 2500/04 : Screening involving studying the effect of compounds C directly on molecule A (e.g. C are potential ligands for a receptor A, or potential substrates for an enzyme A)
• CPC Class Codes: G01N 33/6854 : Immunoglobulins

Abstract

One nonexclusive aspect provides molecules further improved from antibodies that can bind to antigens in an ion concentration-dependent manner. An alternative nonexclusive aspect provides safe and more advantageous Fc region variants that have decreased binding to pre-existing ADA. An alternative nonexclusive aspect provides novel IL-8 antibodies that are superior as pharmaceuticals.

Claims

1-77. -77. (canceled)

78. An isolated nucleic acid encoding an anti-IL-8 antibody which comprises a heavy chain variable region (V_H) and a light chain variable region (V_L), wherein

(a) the V_H comprises:

(i) a HVR-H1 comprising the amino acid sequence of SEQ ID NO;

67,

(ii) a HVR-H2 comprising the amino acid sequence of SEQ ID NO;

73,

(iii) a HVR-H3 comprising the amino acid sequence of SEQ ID NO;

74; and

(b) the V_L comprises;

(i) a HVR-L1 comprising the amino acid sequence of SEQ ID NO;

70,

(ii) a HVR-L2 comprising the amino acid sequence of SEQ ID NO;

75, and

(iii) a HVR-L3 comprising the amino acid sequence of SEQ ID NO;

76.

79. The nucleic acid of claim 78, which is DNA or RNA.

80. The nucleic acid of claim 78, wherein the encoded anti-IL-8 antibody is an IgG antibody.

81. The nucleic acid of claim 80, wherein the encoded IgG antibody is IgG1, IgG2, IgG3 or IgG4.

82. The nucleic acid of claim 81, wherein the encoded IgG antibody is IgG1.

83. The nucleic acid of claim 78, wherein the encoded anti-IL-8 antibody comprises one or more amino acid substitutions selected from:

L235R, G236R, S239K, A327G, A330S, P331S, M428L, N434A, Y436T, Q438R, and S440E, according to EU numbering.

84. The nucleic acid of claim 78, wherein the encoded anti-IL-8 antibody comprises amino acid substitution N434A according to EU numbering.

85. The nucleic acid of claim 78, wherein the encoded anti-IL-8 antibody comprises amino acid substitutions of L235R, G236R, S239K, M428L, N434A, Y436T, Q438R, and S440E, according to EU numbering.

86. The nucleic acid of claim 78, wherein the encoded anti-IL-8 antibody comprises amino acid substitutions of L235R, G236R, A327G, A330S, P331S, M428L, N434A, Y436T, Q438R, and S440E, according to EU numbering.

87. A vector comprising the nucleic acid of claim 78.

88. The vector of claim 87, which is an expression vector.

89. A host cell comprising the expression vector of claim 88.

90. The host cell of claim 89, wherein the nucleic acid encoding the VH and the nucleic acid encoding the VL are in different vectors.

91. A method for producing an anti-IL-8 antibody, comprising culturing the host cell of claim 89 under conditions wherein the nucleic acid coding sequence is expressed, thereby producing the antibody;

and collecting the antibody from the cell culture.

92. An isolated nucleic acid encoding an anti-IL-8 antibody which comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:

78 and a light chain variable region comprising the amino acid sequence of SEQ ID NO;

79.

93. The nucleic acid of claim 92, which is DNA or RNA.

94. The nucleic acid of claim 92, wherein the encoded anti-IL-8 antibody is an IgG antibody.

95. The nucleic acid of claim 94, wherein the encoded IgG antibody is IgG1, IgG2, IgG3 or IgG4.

96. The nucleic acid of claim 95, wherein the encoded IgG antibody is IgG1.

97. The nucleic acid of claim 92, wherein the encoded anti-IL-8 antibody comprises one or more amino acid substitutions selected from:

L235R, G236R, S239K, A327G, A330S, P331S, M428L, N434A, Y436T, Q438R, and S440E, according to EU numbering.

98. The nucleic acid of claim 92, wherein the encoded anti-IL-8 antibody comprises amino acid substitution N434A according to EU numbering.

99. The nucleic acid of claim 92, wherein the encoded anti-IL-8 antibody comprises amino acid substitutions of L235R, G236R, S239K, M428L, N434A, Y436T, Q438R, and S440E, according to EU numbering.

100. The nucleic acid of claim 92, wherein the encoded anti-IL-8 antibody comprises amino acid substitutions of L235R, G236R, A327G, A330S, P331S, M428L, N434A, Y436T, Q438R, and S440E, according to EU numbering.

101. The nucleic acid of claim 92, wherein the encoded anti-IL-8 antibody has a heavy chain comprising an amino acid sequence selected from:

(a) SEQ ID NO;

80;

(b) SEQ ID NO;

81;

(c) SEQ ID NO;

92; and

(d) SEQ ID NO;

93.

102. The nucleic acid of claim 92, wherein the encoded anti-IL-8 antibody has a light chain comprising the amino acid sequence of SEQ ID NO:

82.

103. The nucleic acid of claim 92, wherein the encoded anti-IL-8 antibody has a light chain comprising the amino acid sequence of SEQ ID NO:

82 and a heavy chain comprising an amino acid sequence selected from;

(a) SEQ ID NO;

80;

(b) SEQ ID NO;

81;

(c) SEQ ID NO;

92; and

(d) SEQ ID NO;

93.

104. The nucleic acid of claim 92, wherein the encoded anti-IL-8 antibody has a light chain comprising the amino acid sequence of SEQ ID NO:

82 and a heavy chain comprising the amino acid sequence of SEQ ID NO;

80.

105. The nucleic acid of claim 92, wherein the encoded anti-IL-8 antibody has a light chain comprising the amino acid sequence of SEQ ID NO:

82 and a heavy chain comprising the amino acid sequence of SEQ ID NO;

81.

106. A vector comprising the nucleic acid of claim 92.

107. The vector of claim 106, which is an expression vector.

108. A host cell comprising the expression vector of claim 107.

109. The host cell of claim 108, wherein the nucleic acid encoding the VH and the nucleic acid encoding the VL are in different vectors.

110. A method for producing an anti-IL-8 antibody, comprising culturing the host cell of claim 108 under conditions wherein the nucleic acid coding sequence is expressed, thereby producing the antibody;

and collecting the antibody from the cell culture.