IP Library › Granted Patent US 12,552,866
Granted Patent B2
US 12,552,866 · App. 17/436,629 · Granted Feb 17, 2026

Internalizing binding molecules targeting receptors involved in cell proliferation or in cell differentiation

Inventors: Hendrik Jan Houthoff (Amsterdam, NL); Paulus Martinus Petrus van Bergen en Henegouwen (Utrecht, NL); Niels Jurriaan Sijbrandi (Utrecht, NL); Joey Armand Muns (Hoofddorp, NL); Jan Hendrik Schooten (Utrecht, NL); Sebas Daniël Pronk (Utrecht, NL)
Assignee: LinXis B.V.
C07K16/2863A61K47/6849A61K47/6879A61K2039/505C07K2317/31C07K2317/35C07K2317/569C07K2317/77C07K2317/92C07K2317/94
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Quick Facts
Patent No.
US 12,552,866
App. No.
17/436,629
Granted
Feb 17, 2026
Kind
B2
Abstract

The invention relates to the field of binding molecules comprising at least one single variable antibody domain, targeted at receptors present on myofibroblasts and/or hepatic stellate cells (HSCs). The invention also relates to a binding molecule comprising at least two single variable antibody domains, each targeting a receptor on HSCs and/or on myofibroblasts. The invention further relates to nucleic acids encoding such binding molecules, a host cell for expression of such binding molecules and to methods for preparing such binding molecules. The invention further relates to pharmaceutical compositions that comprise such binding molecule and to uses of such binding molecules and/or compositions, in particular for prophylactic, therapeutic or diagnostic purposes.

Claims (23)

1 . A multiparatopic antibody comprising at least two single variable antibody domains, independently from one another, able to specifically bind to platelet-derived growth factor receptor beta (PDGFRB), wherein:

the first single variable antibody domain comprises a CDR 1 sequence according SEQ ID NO: 11, a CDR 2 sequence according to SEQ ID NO: 13 and a CDR 3 sequence according to SEQ ID NO: 15;

and wherein

the second single variable antibody domain comprises:

a CDR 1 sequence according SEQ ID NO: 67, a CDR 2 sequence according to SEQ ID NO: 69 and a CDR 3 sequence according to SEQ ID NO: 71, or

a CDR 1 sequence according SEQ ID NO: 83, a CDR 2 sequence according to SEQ ID NO: 85 and a CDR 3 sequence according to SEQ ID NO: 87, or

a CDR 1 sequence according SEQ ID NO: 155, a CDR 2 sequence according to SEQ ID NO: 157 and a CDR 3 sequence according to SEQ ID NO: 159.

2 . The antibody according to claim 1 , wherein the second single variable antibody domain comprises a CDR 1 sequence according SEQ ID NO: 155, a CDR 2 sequence according to SEQ ID NO: 157 and the CDR 3 sequence according to SEQ ID NO: 159.

3 . The antibody according to claim 1 , wherein the at least two single variable antibody domains are of VHH-type.

4 . The antibody according to claim 1 , wherein the at least two single variable antibody domains are humanized or camelized.

5 . The antibody, according to claim 1 , wherein the first single variable antibody domain comprises or consists of SEQ ID NO: 9 (SP02P), and wherein the second single variable antibody domain comprises or consists of any one of SEQ ID NOs: SEQ ID NO: 65 (SP12P), SEQ ID NO: 81 (SP14P) and SEQ ID NO: 153 (SP26P).

6 . The antibody according to claim 1 , wherein the first single variable antibody domain comprises or consists of SEQ ID NO: 9 (SP02P) and wherein the second single variable antibody domain comprises or consists of SEQ ID NO: 153 (SP26P).

7 . The antibody according to claim 1 , wherein the antibody is a biparatopic antibody.

8 . The antibody according to claim 1 , further comprising a half-life extender.

9 . The antibody according to claim 1 , wherein the at least two single variable antibody domains are separated by a linker amino acid sequence.

10 . The antibody according to claim 1 , further comprising an N-terminal or a C-terminal cysteine or histidine residue.

11 . A multiparatopic binding molecule comprising the antibody according to claim 1 and further comprising at least one diagnostic or therapeutic molecule.

12 . The binding molecule according to claim 9 , wherein the therapeutic or diagnostic molecule are bound to at least one single variable antibody domain of the antibody by a linker and/or spacer.

13 . The binding molecule according to claim 9 , wherein the therapeutic molecule is a kinase inhibitor.

14 . The binding molecule according to claim 9 , wherein the therapeutic molecule is a toxin.

15 . A nucleic acid that encodes the antibody according to claim 1 and/or the binding molecule according to claim 9 .

16 . A pharmaceutical composition comprising the antibody according to claim 1 and/or the binding molecule according to claim 9 and further comprising at least one pharmaceutically acceptable excipient.

17 . The binding molecule according to claim 9 , comprising a diagnostic molecule, wherein the diagnostic molecule is an imaging agent.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 11, 2021
From: HOUTHOFF, HENDRIK JAN; VAN BERGEN EN HENEGOUWEN, PAULUS MARTINUS PETRUS; SIJBRANDI, NIELS JURRIAAN; MUNS, JOEY ARMAND; SCHOOTEN, JAN HENDRIK; PRONK, SEBAS DANIËL
To: LINXIS B.V.
Reel/Frame 058103/0366 →
Priority Claims (1)
NL 2022702 · Mar 8, 2019 · national
Continuity (1)
Related Publication 20220143204A1 · May 12, 2022
References Cited (22)
US 9650444B2 · Wiegand et al. · 2017 [cited by applicant]
US 10106614B2 · Stanimirovic et al. · 2018 [cited by applicant]
US 20110282033A1 · Gonzalez Pajuelo et al. · 2011 [cited by applicant]
JP 2017514456A · 2017 [cited by applicant]
WO 2016124781A1 · 2016 [cited by applicant]
Proc. Natl. Acad. Sci. USA, 79(6):1979-1983, Mar. 1982 (Year: 1982). [cited by examiner]
Molecular Immunology, 2007, vol. 44, pp. 1075-1084 (Year: 2007). [cited by examiner]
Biochemical and Biophysical Research Communications, 2003, vol. 307, pp. 198-205 (Year: 2003). [cited by examiner]
Colman P. M. (Research in Immunology, 145:33-36, 1994) (Year: 1998). [cited by examiner]
Klaas Poelstra et al: “Drug targeting to the diseased liver”, Journal of Controlled Release, Elsevier, Amsterdam, NL, vol. 161, No. 2, Feb. 11, 2012 (Feb. 11, 2012), pp. 188-197. [cited by applicant]
Yazdani Saleh et al.: “Drug targeting to myofibroblasts: Implications for fibrosis and cancer”, Advanced Drug Delivery Reviews, vol. 121, Jul. 16, 2017 (Jul. 16, 2017), pp. 101-116. [cited by applicant]
Thomas Longerich et al: “Tumor induced local fibrogenic effect by hepatic metastasis of insulinoma”, Virchows Archiv, Springer, Berlin, DE, vol. 446, No. 6, Jun. 1, 2005 (Jun. 1, 2005), pp. 680-681. [cited by applicant]
Crespo Yanguas Sara et al: “Experimental models of liver fibrosis”, Archives of Toxicology, Springer. DE, vol. 90, No. 5, Jun. 6, 2015 (Jun. 6, 2015), pp. 1025-1048. [cited by applicant]
Peter Bannas et al: Nanobodies and Nanobody-Based Human Heavy Chain Antibodies As Antitumor Therapeutics, Frontiers in Immunology, vol. 8. Nov. 22, 2017 (Nov. 22, 2017). [cited by applicant]
Dong Rui et al: Endosome-ER Contacts Control Actin Nucleation and Retromer Function through VAP-Dependent Regulation of PI4P, Cell, Elsevier, Amsterdam, NL, vol. 166, No. 2, Jul. 14, 2016 (Jul. 14, 2016), pp. 408-423. [cited by applicant]
Heukers, Raimond, et al. “Endocytosis of EGFR requires its kinase activity and N-terminal transmembrane dimerization motif.” Journal of cell science 126.21 (2013): 4900-4912. [cited by applicant]
Van Dijk, F., et al. “The antifibrotic potential of a sustained release formulation of a PDGFβ-receptor targeted rho kinase inhibitor.” Journal of Controlled Release 296 (2019): 250-257. [cited by applicant]
Bart Nijmeijer—Slide deck Development of first-in-class nanobody-drug conjugates for the targeted therapy of Liver Fibrosis and Cirrhosis—presented by applicant on Nov. 7, 2019 on the ATDC in Belfast. [cited by applicant]
“Final Oral & Poster Programme” ATDC 2019 Belfast—published by third party on the internet on Jul. 6, 2022. [cited by applicant]
B. Nijmeijer, E. Schooten, S. Pronk, P.J.G.M Steverink, P. Van Bergen en Henegouwen, H.J. Houthoff, Development of first-in-class nanobody-drug conjugates for the targeted therapy of Liver Fibrosis and Cirrhosis—Publish… [cited by applicant]
Strop, Pavel, et al. “Location matters: site of conjugation modulates stability and pharmacokinetics of antibody drug conjugates.” Chemistry & biology 20.2 (2013): 161-167. [cited by applicant]
Nejadmoghaddam, Mohammad-Reza, et al. “Antibody-drug conjugates: possibilities and challenges.” Avicenna journal of medical biotechnology 11.1 (2019): 3. [cited by applicant]