Anti-ROR1 antibodies
The present invention relates to a human or humanized antibody, or an antibody-based binding protein, modified antibody format retaining target binding capacity, antibody derivative or fragment retaining target binding capacity, which targets Receptor tyrosine kinase-like orphan receptor-1 (ROR1). It further relates to bi- or multispecific antibodies, to Immunoligand-Drug Conjugates, to Chimeric Antigen Receptors and to T-cells comprising such Chimeric Antigen Receptors.
1. A humanized antibody, antibody derivative or antibody fragment retaining target binding capacity, which targets Receptor tyrosine kinase-like orphan receptor-1 (ROR1) and comprises three heavy chain CDR sequences consisting of amino acid sequences:
SEQ ID NO. 29 (CDR1 HC),
SEQ ID NO. 30 (CDR2 HC), and
SEQ ID NO. 31 (CDR3 HC), respectively,
and three light chain CDR sequences consisting of amino acid sequences:
SEQ ID NO. 32 (CDR1 LC),
SEQ ID NO. 33 (CDR2 LC), and
SEQ ID NO. 34 (CDR3 LC), respectively,
and which comprises a heavy chain variable region sequence that is at least 95% identical to a sequence selected from the group consisting of
SEQ ID NO. 37, SEQ ID NO. 39, SEQ ID NO. 41, and SEQ ID NO. 43, and
a light chain variable region sequence that is at least 95% identical to a sequence selected from the group consisting of
SEQ ID NO. 38, SEQ ID NO. 40, SEQ ID NO. 42, and SEQ ID NO. 44.
2. The antibody, antibody derivative or antibody fragment according to claim 1 , which comprises a heavy chain variable region sequence and a light chain variable sequence according to
SEQ ID NO. 37 and SEQ ID NO. 38, or
SEQ ID NO. 39 and SEQ ID NO. 40, or
SEQ ID NO. 41 and SEQ ID NO. 42, or
SEQ ID NO. 43 and SEQ ID NO. 44.
3. The antibody according to claim 2 , wherein the antibody is selected from the group consisting of huR12-4, huR12-7, huR12-11, and huR12-16.
4. An Immunoligand-Drug Conjugate having the general formula A-(L)n-(T)m, in which
(a) A is a humanized antibody, wherein the antibody is selected from the group consisting of huR12-4, huR12-7, huR12-11, and huR12-16
(b) L is a linker, and
(c) T is a toxin
and in which n and m are integers between ≥1 and ≤10.
5. An Immunoligand-Drug Conjugate having the general formula A-(L)n-(T)m, in which
(a) A is a humanized anti-ROR-1 antibody,
wherein the humanized anti-ROR1 antibody comprises:
at least one heavy chain variable region that comprises a sequence selected from the group consisting of SEQ ID NO: 37, SEQ ID NO: 39, SEQ ID NO: 41, and SEQ ID NO: 43; and
at least one light chain variable region that comprises a sequence selected from the group consisting of SEQ ID NO: 38, SEQ ID NO: 40, SEQ ID NO: 42, and SEQ ID NO: 44,
(b) L is a linker, and
(c) T is a PNU-derived anthracycline,
in which amino acid sequences of A, of L, if comprising amino acids, and of T, if comprising amino acids, are from N-terminus to C-terminus, and in which n and m are integers between ≥1 and ≤10.
6. The Immunoligand-Drug Conjugate according to claim 5 , wherein the antibody, antibody derivative or antibody fragment comprises a heavy chain variable region sequence and a light chain variable sequence according to
SEQ ID NO. 37 and SEQ ID NO. 38, or
SEQ ID NO. 39 and SEQ ID NO. 40, or
SEQ ID NO. 41 and SEQ ID NO. 42, or
SEQ ID NO. 43 and SEQ ID NO. 44.
7. The Immunoligand-Drug Conjugate according to claim 6 , wherein the antibody is selected from the group consisting of huR12-4, huR12-7, huR12-11, and huR12-16.
8. A pharmaceutical composition comprising the Immunoligand-Drug Conjugate according to claim 5 , together with one or more pharmaceutically acceptable ingredients.