Methods and agents for the treatment of ocular disease
This disclosure relates generally to methods and agents for treating an ocular disease or disorder. More particularly, the present disclosure relates to the use of CD14 antagonist antibodies for treating an ocular disease or disorder.
1. A method for reducing ocular fibrosis in a subject with wet age-related macular degeneration (AMD) who has ocular fibrosis, comprising administering to the eye of the subject amount of a CD14 antagonist antibody effective to reduce ocular fibrosis in the subject, wherein the CD14 antagonist antibody comprises:
a) an antibody VL domain, or antigen binding fragment thereof, comprising L-CDR1, L-CDR2 and L-CDR3, wherein L-CDR1 comprises the sequence RASESVDSYVNSFLH [SEQ ID NO: 13], L-CDR2 comprises the sequence RASNLQS [SEQ ID NO: 14], and L-CDR3 comprises the sequence QQSNEDPYT [SEQ ID NO: 27]; and
b) an antibody VH domain, or antigen binding fragment thereof, comprising H-CDR1, H-CDR2 and H-CDR3, wherein H-CDR1 comprises the sequence SDSAWN [SEQ ID NO: 16], H-CDR2 comprises the sequence YISYSGSTSYNPSLKS [SEQ ID NO: 17], and H-CDR3 comprises the sequence GLRFAY [SEQ ID NO: 18], and
wherein the CD14 antagonist antibody is either administered alone or in combination with an anti-VEGF agents.
2. The method of claim 1 , wherein the CD14 antagonist antibody comprises:
a light chain comprising the amino acid
sequence:
[SEQ ID NO: 28]
QSPASLAVSLGQRATISCRASESVDSYVNSFLHWYQQKPGQPPKLLIYRA
SNLQSGIPARFSGSGSRTDFTLTINPVEADDVATYYCQQSNEDPYTFGGG
TKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVD
NALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGL
SSPVTKSFNRGEC
and
a heavy chain comprising the amino acid
sequence:
[SEQ ID NO: 29]
LQQSGPGLVKPSQSLSLTCTVTGYSITSDSAWNWIRQFPGNRLEWMGYIS
YSGSTSYNPSLKSRISITRDTSKNQFFLQLNSVTTEDTATYYCVRGLRFA
YWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVT
VSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHK
PSNTKVDKRVESKYGPPCPSCPAPEFLGGPSVFLFPPKPKDTLMISRTPE
VTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTV
LHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEM
TKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYS
RLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK;
or
a light chain comprising the amino acid
sequence:
[SEQ ID NO: 32]
DIVLTQSPASLAVSLGQRATISCRASESVDSYVNSFLHWYQQKPGQPPKL
LIYRASNLQSGIPARFSGSGSRTDFTLTINPVEADDVATYYCQQSNEDPY
TFGGGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKV
QWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEV
THQGLSSPVTKSFNRGEC
and
a heavy chain comprising the amino acid
sequence:
[SEQ ID NO: 33]
DVQLQQSGPGLVKPSQSLSLTCTVTGYSITSDSAWNWIRQFPGNRLEWMG
YISYSGSTSYNPSLKSRISITRDTSKNQFFLQLNSVTTEDTATYYCVRGL
RFAYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPE
PVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNV
DHKPSNTKVDKRVESKYGPPCPSCPAPEFLGGPSVFLFPPKPKDTLMISR
TPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSV
LTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQ
EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFF
LYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK.
3. The method of claim 2 , wherein the CD14 antagonist antibody is IC14.
4. The method of claim 3 , wherein IC14 is administered in combination with an anti-VEGF agent.
5. The method of claim 4 , wherein the anti-VEGF agent is selected from the group consisting of an anti-VEGF antibody, anti-VEGF antibody mimetic, VEGF Trap molecule, soluble fms-like tyrosine kinase-1, and a tyrosine kinase inhibitor.
6. The method of claim 5 , wherein the anti-VEGF antibody is selected from the group consisting of brolicizumab, ranibizumab and faricimab.
7. The method of claim 5 , wherein the VEGF Trap molecule is aflibercept or conbercept.
8. The method of claim 5 , wherein the VEGF antibody mimetic is abicipar pegol.
9. The method of claim 5 , wherein the tyrosine kinase inhibitor is a Tie2 inhibitor or an Ang-2 inhibitor.
10. The method of claim 4 , wherein the subject has received an anti-VEGF agent for at least 3, 6, 9, 12, 14, 16 or 18 months.
11. The method of claim 1 , wherein the subject has received an anti-VEGF agent for at least 3, 6, 9, 12, 14, 16 or 18 months.
12. The method of claim 1 , wherein the anti-VEGF agent is selected from the group consisting of an anti-VEGF antibody, anti-VEGF antibody mimetic, VEGF Trap molecule, soluble fms-like tyrosine kinase-1, or a tyrosine kinase inhibitor.
13. The method of claim 12 , wherein the anti-VEGF antibody is selected from the group consisting of brolicizumab, ranibizumab and faricimab.
14. The method of claim 12 , wherein the VEGF Trap molecule is aflibercept or conbercept.
15. The method of claim 12 , wherein the anti-VEGF antibody mimetic is abicipar pegol.
16. The method of claim 12 , wherein the tyrosine kinase inhibitor is a Tie2 inhibitor or an Ang-2 inhibitor.