US 2026/0308263 A1 · COLONY STIMULATING FACTOR 1 RECEPTOR ANTIBODIES AND METHODS OF USE THEREOF

Abstract

The present disclosure provides, among other things, anti-CSF1R single-domain antibodies (sdAbs) with high affinity to CSF1R (e.g., KD of pM to low nM) and therapeutic uses of such sdAbs in effectively treating CSF1R mediated diseases, such as age-related macular degeneration (AMD). In some embodiments, an anti-CSF1R sdAb is fused to an Fc region.

A single domain antibody (sdAb) that binds to colony stimulating factor 1 receptor (CSF1R), wherein the sdAb comprises

a. a CDR1 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from GGTFSYY (SEQ ID NO:
106), a CDR2 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from SQYGSN (SEQ ID NO:
109), and a CDR3 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from LRSGSDWRTIRDYDN (SEQ ID NO:
112);
or
b. a CDR1 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from AASGGTFSYYNMG (SEQ ID NO:
124), a CDR2 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from VISQYGSNTY (SEQ ID NO:
127), and a CDR3 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from ATLRSGSDWRTIRDYDN (SEQ ID NO:
130);
or
c. a CDR1 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from GGTFSYYN (SEQ ID NO:
115), a CDR2 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from ISQYGSNT (SEQ ID NO:
118), and a CDR3 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from ATLRSGSDWRTIRDYDN (SEQ ID NO:
121);
or
d. a CDR1 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from YYNMG (SEQ ID NO:
133), a CDR2 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from VISQYGSNTYYADSVKG (SEQ ID NO:
136), and a CDR3 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from LRSGSDWRTIRDYDN (SEQ ID NO:
139);
or
e. a CDR1 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from GDIFSFN (SEQ ID NO:
107), a CDR2 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from APGGN (SEQ ID NO:
110), and a CDR3 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from WPFSRDS (SEQ ID NO:
113);
or
f. a CDR1 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from AASGDIFSFNVMG (SEQ ID NO:
125), a CDR2 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from TIAPGGNTN (SEQ ID NO:
156), and a CDR3 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from NRWPFSRDS (SEQ ID NO:
131);
or
g. a CDR1 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from AASGDIFSFNVMG (SEQ ID NO:
125), a CDR2 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from VIAPGGNTY (SEQ ID NO:
128), and a CDR3 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from NRWPFSRDS (SEQ ID NO:
131);
or
h. a CDR1 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from GDIFSFNV (SEQ ID NO:
116), a CDR2 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from IAPGGNT (SEQ ID NO:
119), and a CDR3 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from NRWPFSRDS (SEQ ID NO:
122);
or
i. a CDR1 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from FNVMG (SEQ ID NO:
134), a CDR2 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from TIAPGGNTNYFDSARG (SEQ ID NO:
157), and a CDR3 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from WPFSRDS (SEQ ID NO:
140);
or
j. a CDR1 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from FNVMG (SEQ ID NO:
134), a CDR2 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from VIAPGGNTYYADSVKG (SEQ ID NO:
137), and a CDR3 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from WPFSRDS (SEQ ID NO:
140);
or
k. a CDR1 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from GMAFGSS (SEQ ID NO:
108), a CDR2 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from TSAGY (SEQ ID NO:
111), and a CDR3 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from GPFHSTAYST (SEQ ID NO:
114);
or
l. a CDR1 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from VASGMAFGSSPMN (SEQ ID NO:
126), a CDR2 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from GVTSAGYAY (SEQ ID NO:
129), and a CDR3 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from ARGPFHSTAYST (SEQ ID NO:
132);
or
m. a CDR1 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from GMAFGSSP (SEQ ID NO:
117), a CDR2 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from VTSAGYA (SEQ ID NO:
120), and a CDR3 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from ARGPFHSTAYST (SEQ ID NO:
123);
or
n. a CDR1 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from SSPMN (SEQ ID NO:
135), a CDR2 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from GVTSAGYAYYADWVKG (SEQ ID NO:
138), and a CDR3 comprising an amino acid sequence that is identical to or differs by no more than 2 amino acid residues from GPFHSTAYST (SEQ ID NO:
141).

66 more elements

Colony stimulating factor 1 receptor antibodies and methods of use thereof

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Colony stimulating factor 1 receptor antibodies and methods of use thereof

Life of this patent

Abstract

Claims28