IP Library › Granted Patent US 12,590,151
Granted Patent B2
US 12,590,151 · App. 18/052,526 · Granted Mar 31, 2026

Anti-human CD19 antibodies with high affinity

Inventors: Thomas Hofer (Zürich, CH); Claudia Ferrara Koller (Zug, CH); Ekkehard Moessner (Kreuzlingen, CH); Mi He (Zürich, CH)
Assignee: Hoffmann-La Roche Inc.
C07K16/2803A61P35/00C07K16/3061C07K2317/24C07K2317/31C07K2317/33C07K2317/56C07K2317/565C07K2317/92
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 12,590,151
App. No.
18/052,526
Granted
Mar 31, 2026
Kind
B2
Abstract

The present invention relates to antibodies against human CD19 (anti-human CD19 antibodies), methods for their production, pharmaceutical compositions containing these antibodies, and methods of using the same.

Claims (32)

1 . An antibody that specifically binds to human CD19, wherein the antibody comprises

(a) CDR-L1 comprising the amino acid sequence of SEQ ID NO: 43,

(b) CDR-L2 comprising the amino acid sequence of SEQ ID NO: 44,

(c) CDR-L3 comprising the amino acid sequence of SEQ ID NO: 45,

(d) CDR-H1 comprising the amino acid sequence of SEQ ID NO: 46,

(e) CDR-H2 comprising the amino acid sequence of SEQ ID NO: 47, and

(f) CDR-H3 comprising the amino acid sequence of SEQ ID NO: 48.

2 . The antibody of claim 1 , wherein the antibody is a monoclonal antibody.

3 . The antibody of claim 1 , wherein the antibody is a humanized or chimeric antibody.

4 . The antibody of claim 1 , wherein the antibody is an antibody fragment that specifically binds to human CD19.

5 . The antibody of claim 1 , wherein the antibody comprises a VH domain comprising an amino acid sequence of SEQ ID NO:99 and a VL domain comprising an amino acid sequence of SEQ ID NO:100.

6 . The antibody of claim 1 , which is a full length IgG1 antibody.

7 . The antibody of claim 1 , which is a full length IgG1 antibody with mutations L234A, L235A, and P329G, numbering accordingly to the EU index of Kabat.

8 . The antibody of claim 1 , wherein the antibody is cross reactive for human and cynomolgus CD19.

9 . The antibody of claim 1 , wherein said antibody is a bispecific antibody that specifically binds to human CD19 and to a second antigen.

10 . A polynucleotide encoding the antibody of claim 1 .

11 . A vector comprising the polynucleotide according to claim 10 .

12 . A host cell comprising the vector of claim 11 .

13 . A method of producing the antibody of claim 1 , comprising the steps of (i) culturing the host cell of claim 12 under conditions suitable for expression of the antibody, and (ii) recovering the antibody.

14 . A pharmaceutical formulation comprising the antibody of claim 1 and a pharmaceutically acceptable carrier.

15 . A method of treating a disease in an individual, comprising

administering to the individual a therapeutically effective amount of the antibody of claim 1 .

16 . The method of claim 15 , wherein the disease is a B-cell cancer.

17 . The method of claim 15 , wherein the disease is an autoimmune disease, rheumatoid arthritis, lupus, psoriasis, and a bone disease.

18 . A polynucleotide encoding the antibody of claim 9 .

19 . A vector comprising the polynucleotide according to claim 18 .

20 . A host cell comprising the vector of claim 19 .

21 . A method of producing the antibody of claim 9 , comprising the steps of (i) culturing the host cell of claim 12 under conditions suitable for expression of the antibody, and (ii) recovering the antibody.

22 . A pharmaceutical formulation comprising the antibody of claim 9 and a pharmaceutically acceptable carrier.

23 . A method of treating a CD-19-expressing disease in an individual, comprising administering to the individual a therapeutically effective amount of the antibody of claim 10 .

24 . The method of claim 23 , wherein the disease is a B-cell cancer.

25 . The method of claim 15 , wherein the disease is an autoimmune disease, rheumatoid arthritis, lupus, psoriasis, or a bone disease.

Assignments (6)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 4, 2023
From: FERRARA KOLLER, CLAUDIA; HOFER, THOMAS; MOESSNER, EKKEHARD; HE, MI
To: ROCHE GLYCART AG
Reel/Frame 063212/0540 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 4, 2023
From: ROCHE GLYCART AG
To: F. HOFFMANN-LA ROCHE AG
Reel/Frame 063212/0549 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 4, 2023
From: F. HOFFMANN-LA ROCHE AG
To: HOFFMANN-LA ROCHE INC.
Reel/Frame 063212/0562 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 4, 2023
From: FERRARA KOLLER, CLAUDIA; HOFER, THOMAS; MOESSNER, EKKEHARD; HE, MI
To: ROCHE GLYCART AG
Reel/Frame 063212/0589 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 4, 2023
From: ROCHE GLYCART AG
To: F. HOFFMANN-LA ROCHE AG
Reel/Frame 063212/0599 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 4, 2023
From: F. HOFFMANN-LA ROCHE AG
To: HOFFMANN-LA ROCHE INC.
Reel/Frame 063212/0630 →
Priority Claims (2)
EP 15188262 · Oct 2, 2015 · regional
EP 16167893 · May 2, 2016 · regional
Continuity (4)
Continuation 16689880 · Nov 20, 2019
Continuation 15941519 · Mar 30, 2018
Continuation PCTEP2016073062 · Sep 28, 2016
Related Publication 20230312710A1 · Oct 5, 2023
References Cited (85)
US 5565332A · Hoogenboom et al. · 1996 [cited by applicant]
US 5731168A · Carter et al. · 1998 [cited by applicant]
US 5821333A · Carter et al. · 1998 [cited by applicant]
US 5869046A · Presta et al. · 1999 [cited by applicant]
US 6171586B1 · Lam et al. · 2001 [cited by applicant]
US 6267958B1 · Andya et al. · 2001 [cited by applicant]
US 6737056B1 · Presta et al. · 2004 [cited by applicant]
US 6982321B2 · Winter et al. · 2006 [cited by applicant]
US 7087409B2 · Barbas et al. · 2006 [cited by applicant]
US 7332581B2 · Presta et al. · 2008 [cited by applicant]
US 7521541B2 · Eigenbrot et al. · 2009 [cited by applicant]
US 7527791B2 · Adams et al. · 2009 [cited by applicant]
US 7695936B2 · Carter et al. · 2010 [cited by applicant]
US 8097703B2 · Rao-Naik et al. · 2012 [cited by applicant]
US 8323653B2 · Damschroder et al. · 2012 [cited by applicant]
US 8524867B2 · Bernett et al. · 2013 [cited by applicant]
US 8883992B2 · Damschroder et al. · 2014 [cited by applicant]
US 20040132028A1 · Stumpp et al. · 2004 [cited by applicant]
US 20060233791A1 · Tedder et al. · 2006 [cited by applicant]
KR 20090059149A · 2009 [cited by applicant]
KR 20120099647A · 2012 [cited by applicant]
WO 02020565A2 · 2002 [cited by applicant]
WO 03048209A1 · 2003 [cited by applicant]
WO 2006044908A2 · 2006 [cited by applicant]
WO 2006089133A2 · 2006 [cited by applicant]
WO 200702223A2 · 2007 [cited by applicant]
WO 2008022152A2 · 2008 [cited by applicant]
WO WO2008022152 · 2008 [cited by examiner]
WO 2008031056A2 · 2008 [cited by applicant]
WO 2010095031A2 · 2010 [cited by applicant]
WO WO2011051307A1 · 2011 [cited by applicant]
WO 2011147834A1 · 2011 [cited by applicant]
WO 2012010561A1 · 2012 [cited by applicant]
WO 2012130831A1 · 2012 [cited by applicant]
WO 2015130766A1 · 2015 [cited by applicant]
WO 2016048938A1 · 2016 [cited by applicant]
WO 2016075278A1 · 2016 [cited by applicant]
WO WO2016075278 · 2016 [cited by examiner]
WO 2017055541A1 · 2017 [cited by applicant]
Almagro, J., et al., “Humanization of antibodies” Front Biosci 13(5):1619-1633 (Jan. 1, 2008). [cited by applicant]
Bonifacino, J., et al., “Commonly Used Techniques: Molecular Biology Techniques” Curr Protocols in Cell Biol 8(1):1-4 (Oct. 1, 2000). [cited by applicant]
Carter, R., et al., “Roles of CD19 Signal Transduction in B Cell Biology” Immunol Res 26(1-3):45-54 (Aug. 1, 2002). [cited by applicant]
Chang, K., et al., “Affinity Maturation of an Epidermal Growth Factor Receptor Targeting Human Monoclonal Antibody ER414 by CDR Mutation” Immune Netw 12(4):155-164 (Aug. 1, 2012). [cited by applicant]
Chothia, C., et al., “Canonical structures for the hypervariable regions of immunoglobulins” J Mol Biol 196(4):901-917 (Aug. 20, 1987). [cited by applicant]
Conry, R., et al., “Phase I trial of an anti-CD19 deglycosylated ricin a chain immunotoxin in non-hodgkin's lymphoma: Effect of an intensive schedule of administration” J Immunother Emphasis Tumor Immunol 18(4):231-241 … [cited by applicant]
Dall'Acqua, W., et al., “Antibody humanization by framework shuffling” Methods 36(1):43-60 (Jan. 17, 2005). [cited by applicant]
Daugherty, P., et al., “Quantitative analysis of the effect of the mutation frequency on the affinity maturation of single chain Fv antibodies” PNAS USA 97(5):2029-2034 (Feb. 29, 2000). [cited by applicant]
Hardcastle, I., et al., “Isoindolinone Inhibitors of the Murine Double Minute 2 (MDM2)-p53 Protein-Protein Interaction: Structure-Activity Studies Leading to Improved Potency” J Med Chem 54(5):1233-1243 (Mar. 10, 2011). [cited by applicant]
Hekman, A., et al., “Initial experience with treatment of human B cell lymphoma with anti-CD 19 monoclonal antibody” Cancer Immunol Immun 32(6):364-372 (Jan. 1, 1991). [cited by applicant]
Hoogenboom, H., et al., “Overview of antibody phage-display technology and its applications” Methods Mol Biol 178:1-37 (Jan. 1, 2002). [cited by applicant]
“International Preliminary Report on Patentability—PCT/EP2016/073062 (Report Issuance Date: Apr. 3, 2018; Chapter I),”: pp. 1-9 (Apr. 12, 2018). [cited by applicant]
“International Search Report—PCT/EP2016/07362” (w/Written Opinion), :pp. 1-17 (Dec. 13, 2016). [cited by applicant]
Jendeberg, L., et al., “Engineering of Fc(1) and Fc(3) from human immunoglobulin G to analyse subclass specificity for staphylococcal protein A” J Immunol Methods 201(1):25-34 (Feb. 14, 1997). [cited by applicant]
Jones, P.T., et al., “Replacing the Complementarity-Determining Regions in a Human Antibody with Those From a Mouse” Nature 321(6069):522-525 (May 29, 1986). [cited by applicant]
Kabat, E., et al. U.S. Dept. of Health and Human Services, Public Health Services, NIH Publ. No. 91-3242:3 “Sequences of Proteins of Immunological Interest” (1983). [cited by applicant]
Kabat, E.A., et al. Sequences of Proteins of Immunological Interest: Tabulation and Analysis of Amino Acid and Nucleic Acid Sequences of Precursors, V-Regions, C-Regions, J-Chain T-Cell Receptors for Antigen, T-Cell Sur… [cited by applicant]
Kashmiri, S., et al., “SDR grafting—a new approach to antibody humanization” Methods 36:25-34 (Jan. 1, 2005). [cited by applicant]
Klimka, A. et al., “Human anti-CD30 recombinant antibodies by guided phage antibody selection using cell panning” Brit J Cancer 83(2):252-260 (Jun. 15, 2000). [cited by applicant]
Kohl, A., et al., “Designed to be stable: Crystal structure of a consensus ankyrin repeat protein” PNAS 100(4):1700-1705 (Feb. 18, 2003). [cited by applicant]
Lonberg, N., et al., “Fully human antibodies from transgenic mouse and phage display platforms” Curr Opin Immunol 20(4):450-459 (Aug. 1, 2008). [cited by applicant]
Lonberg, N.,, “Human antibodies from transgenic animals” Nat Biotechnol 23(9):1117-1125 (Sep. 7, 2005). [cited by applicant]
Manzke, O., et al., “Locoregional treatment of low-grade B-cell lymphoma with CD3xCD19 bispecific antibodies and CD28 costimulation. II. Assessment of cellular immune responses” Int J Cancer 91(4):516-522 (Feb. 15, 2001… [cited by applicant]
Mariuzza, R. et al., “The structural basis of antigen-antibody recognition” Annu Rev Biophys Chem 16:139-159 (Jun. 1, 1987). [cited by applicant]
Merchant, A., et al., “An efficient route to human bispecific IgG” Nat Biotechnol 16(7):677-681 (Jul. 1, 1998). [cited by applicant]
Morrison, S., et al., “Chimeric human antibody molecules: Mouse antigen-binding domains with human constant region domains” PNAS USA 81(21):6851-6855 (Nov. 1, 1984). [cited by applicant]
Morrison, S., et al., “Genetically Engineered Antibody Molecules” Adv Immunol 44:65-92 (Jan. 1, 1989). [cited by applicant]
Osbourn, J., et al., “From rodent reagents to human therapeutics using antibody guided selection” Methods 36:61-68 (May 1, 2005). [cited by applicant]
Padlan, E. et al., “A possible procedure for reducing the immunogenicity of antibody variable domains while preserving their ligand-binding properties” Mol Immunol 28(4-5):489-498 (Apr. 30, 1991). [cited by applicant]
Padlan, E. et al., “Anatomy of the Antibody Molecule” Mol Immunol 31(3):169-217 (Feb. 1, 1994). [cited by applicant]
Ponsel, D., et al., “High Affinity, Develop ability and Functional Size: The Holy Grail of Combinatorial Antibody Library Generation” Molecules 16(5):3675-3700 (May 3, 2011). [cited by applicant]
Queen, C., et al., “A humanized antibody that binds to the interleukin 2 receptor” PNAS USA 86(24):10029-10033 (Dec. 1, 1989). [cited by applicant]
Rajpal, A., et al., “A general method for greatly improving the affinity of antibodies by using combinatorial libraries” PNAS USA 102(24):8466-8471 (Jun. 1, 2005). [cited by applicant]
Remington, J., et al. Remington's Pharmaceutical Sciences (Table of Contents, total in 4 pages), Osol , eds., 16th edition, Easton, PA: Mack Publishing Company, (Jan. 1, 1980). [cited by applicant]
Ridgway, J., et al., “Knobs-into-holes' engineering of antibody CH3 domains for heavy chain heterodimerization” Protein Eng 9(7):617-621 (Jul. 1, 1996). [cited by applicant]
Riechmann, L., et al., “Reshaping human antibodies for therapy” Nature 332:323-327 (Mar. 24, 1988). [cited by applicant]
Roguska, M., et al., “A comparison of two murine monoclonal antibodies humanized by CDR-grafting and variable domain resurfacing” Protein Eng 9(10):895-904 (Oct. 1, 1996). [cited by applicant]
Silacci, M., et al., “Design, construction, and characterization of a large synthetic human antibody phage display library” Proteomics 5(9):2340-2350 (Jun. 1, 2005). [cited by applicant]
Singer, M., et al. Genes and Genomes “Chapter 1.3: Structure of Proteins” (Geny i genomy Moscow: Mir, 1991), Berg, P., ed., Osney Mead, Oxford-UK: Blackwell Scientific Publications,:67-69 (Jan. 1, 1991). [cited by applicant]
Steidl, S., et al., “In vitro affinity maturation of human GM-CSF antibodies by targeted CDR-diversification” Mol Immunol 46(1):135-144 (Nov. 1, 2008). [cited by applicant]
Thie, H. Antibody Engineering “Chapter 26: Affinity Maturation by Random Mutagenesis and Phage Display” Kontermann, R. and Dubel, S., eds., Berlin Heidelberg, DE: Springer-Verlag Berlin, vol. 1:397-409 (Jan. 1, 2010). [cited by applicant]
Van Dijk, M., et al., “Human antibodies as next generation therapeutics” Curr Opin Chem Biol 5(4):368-374 (Aug. 1, 2001). [cited by applicant]
Verhoeyen, M., et al., “Reshaping human antibodies: Grafting an anti-lysozyme activity” Science 239(4847):1534-1536 (Mar. 25, 1988). [cited by applicant]
Vlasveld, L.T., et al., “Treatment of low-grade non-Hodgkin's lymphoma with continuous infusion of low-dose recombinant interleukin-2 in combination with the B-cell-specific monoclonal antibody CLB-CD19” Cancer Immunol … [cited by applicant]
Yang, W. et al., “CDR walking mutagenesis for the affinity maturation of a potent human anti-HIV-1 antibody into the picomolar range” J Mol Biol 254(3):392-403 (Jan. 1, 1995). [cited by applicant]
Yazawa,N., et al., “Immunotherapy using unconjugated CD19 monoclonal antibodies in animal models for B lymphocyte malignancies and autoimmune disease” PNAS 102(42):15178-15183 (Oct. 18, 2005). [cited by applicant]