US 10,647,757 B2Granted

Collection and methods for its use

AssigneeMorphosys AG

InventorsMarkus Enzelberger, Stefanie Urlinger, Thomas Tiller, Josef Prassler, Tanja Herrmann

Life of this patent

Estimating the term…

Abstract

The present disclosure enables methods of identifying the VH and VL class pairs in the human immune repertoire, determining the VH and VL class pairs that are most prevalent and those having favorable biophysical properties. More specifically, the collections of the present disclosure comprise the most prevalent and/or preferred VH and VL class pairings with highly diversified CDRs.

Claims8

Dependent claims

A collection of synthetic antibody fragments comprising variable heavy chain and variable light chain framework regions,

wherein said synthetic antibody fragments are selected from Fab, F(ab′)2, Fab′, Fv, scFv, single chains which include an Fc portion and nanobodies,
wherein said framework regions comprise germline protein sequences,
wherein said germline protein sequences comprise the following properties:
i) four or less post translational modifications in the complementarity determining regions;
ii) two or less methionines in the complementarity determining regions;
iii) one or less unpaired cysteines;
iv) one or less T-cell epitopes;
and
v) an isoelectric point of at least 7.5;
and
wherein said collection of synthetic antibody fragments comprises germline protein sequences of at least two different germline protein pairs, wherein the germline protein pairs are selected from
IGHV1-18 (SEQ ID NO:
65)/IGKV1-05 (SEQ ID NO:
118);
IGHV1-18 (SEQ ID NO:
65)/IGLV2-23 (SEQ ID NO:
174);
IGHV1-46 (SEQ ID NO:
68)/IGKV1-09 (SEQ ID NO:
121);
IGHV1-46 (SEQ ID NO:68)/IGKV1-39 (SEQ ID NO:
129);
IGHV1-46 (SEQ ID NO:
68)/IGKV3-15 (SEQ ID NO:153);
IGHV1-69*01 (SEQ ID NO:
70)/IGKV1-05 (SEQ ID NO:
118);
IGHV3-07 (SEQ ID NO:
77)/IGKV1-09 (SEQ ID NO:
121);
IGHV3-07 (SEQ ID NO:
77)/IGKV1-12 (SEQ ID NO:
122);
IGHV3-07 (SEQ ID NO:
77)/IGKV1-27 (SEQ ID NO:
126);
IGHV3-07 (SEQ ID NO:
77)/IGKV3-15 (SEQ ID NO:
153);
IGHV3-07 (SEQ ID NO:
77)/IGLV1-47 (SEQ ID NO:
167);
IGHV3-07 (SEQ ID NO:
77)/IGLV2-23 (SEQ ID NO:
174);
IGHV3-07 (SEQ ID NO:
77)/IGLV3-01 (SEQ ID NO:
175);
IGHV3-11 (SEQ ID NO:
79)/IGKV1-05 (SEQ ID NO:
118);
IGHV3-11 (SEQ ID NO:
79)/IGKV1-06 (SEQ ID NO:
119);
IGHV3-11 (SEQ ID NO:
79)/IGKV1-12 (SEQ ID NO:
122);
IGHV3-11 (SEQ ID NO:
79)/IGKV1-16 (SEQ ID NO:
124);
IGHV3-11 (SEQ ID NO:
79)/IGKV3-15 (SEQ ID NO:
153);
IGHV3-11 (SEQ ID NO:
79)/IGLV1-47 (SEQ ID NO:
167);
IGHV3-11 (SEQ ID NO:
79)/IGLV2-23 (SEQ ID NO:
174);
IGHV3-15 (SEQ ID NO:
81)/IGKV1-05 (SEQ ID NO:
118);
IGHV3-15 (SEQ ID NO:
81)/IGKV1-06 (SEQ ID NO:
119);
IGHV3-15 (SEQ ID NO:
81)/IGKV1-09 (SEQ ID NO:
121);
IGHV3-15 (SEQ ID NO:
81)/IGKV1-12 (SEQ ID NO:
122);
IGHV3-15 (SEQ ID NO:
81)/IGKV1-16 (SEQ ID NO:
124);
IGHV3-15 (SEQ ID NO:
81)/IGKV1-27 (SEQ ID NO:
126);
IGHV3-15 (SEQ ID NO:
81)/IGKV1-39 (SEQ ID NO:
129);
IGHV3-15 (SEQ ID NO:
81)/IGKV3-15 (SEQ ID NO:
153);
IGHV3-15 (SEQ ID NO:
81)/IGLV1-40 (SEQ ID NO:
165);
IGHV3-15 (SEQ ID NO:
81)/IGLV1-51 (SEQ ID NO:
169);
IGHV3-15 (SEQ ID NO:
81)/IGLV2-11 (SEQ ID NO:
171);
IGHV3-21 (SEQ ID NO:
84)/IGKV1-06 (SEQ ID NO:
119);
IGHV3-21 (SEQ ID NO:
84)/IGKV1-12 (SEQ ID NO:
122);
IGHV3-21 (SEQ ID NO:
84)/IGKV1-27 (SEQ ID NO:
126);
IGHV3-21 (SEQ ID NO:
84)/IGKV1-39 (SEQ ID NO:
129);
IGHV3-21 (SEQ ID NO:
84)/IGLV2-14 (SEQ ID NO:
172);
IGHV3-21 (SEQ ID NO:
84)/IGLV2-23 (SEQ ID NO:
174);
IGHV3-30 (SEQ ID NO:
86)/IGLV2-23 (SEQ ID NO:
174);
IGHV3-30 (SEQ ID NO:
86)/IGLV3-1 (SEQ ID NO:
175);
IGHV3-33 (SEQ ID NO:
89)/IGKV3-15 (SEQ ID NO:
153);
IGHV3-33 (SEQ ID NO:
89)/IGLV2-23 (SEQ ID NO:
174);
IGHV3-48 (SEQ ID NO:
93)/IGKV1-27 (SEQ ID NO:
126);
IGHV3-53 (SEQ ID NO:
95)/IGKV1-09 (SEQ ID NO:
121);
IGHV3-53 (SEQ ID NO:
95)/IGKV1-12 (SEQ ID NO:
122);
IGHV3-53 (SEQ ID NO:
95)/IGLV1-51 (SEQ ID NO:
169);
IGHV3-53 (SEQ ID NO:
95)/IGLV2-23 (SEQ ID NO:
174);
IGHV3-53 (SEQ ID NO:
95)/IGLV3-1 (SEQ ID NO:
175);
IGHV3-74 (SEQ ID NO:
100)/IGKV1-06 (SEQ ID NO:
119);
IGHV3-74 (SEQ ID NO:
100)/IGKV1-09 (SEQ ID NO:
121);
IGHV3-74 (SEQ ID NO:
100)/IGKV1-27 (SEQ ID NO:
126);
IGHV3-74 (SEO ID NO:
100)/IGKV3-15 (SEQ ID NO:
153);
IGHV3-74 (SEQ ID NO:
100)/IGLV1-51 (SEQ ID NO:
169);
IGHV4-04 (SEQ ID NO:
102)/IGLV2-23 (SEQ ID NO:
174);
IGHV4-04 (SEQ ID NO:
102)/IGLV3-1 (SEQ ID NO:
175);
IGHV4-04 (SEQ ID NO:
102)/IGLV3-21 (SEQ ID NO:
182);
IGHV4-39 (SEQ ID NO:
109)/IGLV2-14 (SEQ ID NO:
172);
IGHV4-39 (SEQ ID NO:
109)/IGLV3-1 (SEQ ID NO:
175);
IGHV5-51 (SEQ ID NO:113)/IGKV1-09 (SEQ ID NO:
121);
IGHV5-51 (SEQ ID NO:
113)/IGLV2-23 (SEQ ID NO:
174);
IGHV5-51 (SEQ ID NO:
113)/IGLV3-1 (SEQ ID NO:
175);
IGHV6-1 (SEQ ID NO:115)/IGKV1-06 (SEQ ID NO:
119);
and
IGHV6-1 (SEQ ID NO:
115)/IGLV2-23 (SEQ ID NO:
174).

191 more elements

Dependencies are inferred from the claim text.

Facts

Application: 15/449,561Filed 3 Mar 2017 · division
Priority: EP 0916272429 May 2009
Published: US 2017/0218048 A13 Aug 2017
Granted: 12 May 2020
Term ends: Not estimatedThe source records don’t support an estimate.

Classification15 codes

C07K 16/005
Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies: constructed by phage libraries
C07K 16/00
Immunoglobulins [ig]
C07K 16/32
Against material from animals or humans: against translation products of oncogenes
C12N 15/1093
Isolating an individual clone by screening libraries: general methods of preparing gene libraries, not provided for in other subgroups

Family

Application61/182,350Us provisional application · filed 29 May 2009
Application61/299,401Us provisional application · filed 29 Jan 2010
PCT/EP2010/057507Parent of this division · filed 29 May 2010
Application14/169,162Parent of this division · filed 31 Jan 2014
US 8,685,896 B2Parent of this division · filed 1 Apr 2014
US 2017/0218048 A1Pre-grant publication · published 3 Aug 2017
US 9,624,293 B2Parent of this division
Application13/321,564Parent of this division
US 2012/0077713 A1Published application
US 2014/0163208 A1Published application
US 10,647,757 B2This patent

From the US filing history. Foreign family members aren’t listed.

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Citations

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Abstract

A collection of synthetic antibody fragments comprising variable heavy chain and variable light chain framework regions,

wherein said synthetic antibody fragments are selected from Fab, F(ab′)2, Fab′, Fv, scFv, single chains which include an Fc portion and nanobodies,
wherein said framework regions comprise germline protein sequences,
wherein said germline protein sequences comprise the following properties:
i) four or less post translational modifications in the complementarity determining regions;
ii) two or less methionines in the complementarity determining regions;
iii) one or less unpaired cysteines;
iv) one or less T-cell epitopes;
and
v) an isoelectric point of at least 7.5;
and
wherein said collection of synthetic antibody fragments comprises germline protein sequences of at least two different germline protein pairs, wherein the germline protein pairs are selected from
IGHV1-18 (SEQ ID NO:
65)/IGKV1-05 (SEQ ID NO:
118);
IGHV1-18 (SEQ ID NO:
65)/IGLV2-23 (SEQ ID NO:
174);
IGHV1-46 (SEQ ID NO:
68)/IGKV1-09 (SEQ ID NO:
121);
IGHV1-46 (SEQ ID NO:68)/IGKV1-39 (SEQ ID NO:
129);
IGHV1-46 (SEQ ID NO:
68)/IGKV3-15 (SEQ ID NO:153);
IGHV1-69*01 (SEQ ID NO:
70)/IGKV1-05 (SEQ ID NO:
118);
IGHV3-07 (SEQ ID NO:
77)/IGKV1-09 (SEQ ID NO:
121);
IGHV3-07 (SEQ ID NO:
77)/IGKV1-12 (SEQ ID NO:
122);
IGHV3-07 (SEQ ID NO:
77)/IGKV1-27 (SEQ ID NO:
126);
IGHV3-07 (SEQ ID NO:
77)/IGKV3-15 (SEQ ID NO:
153);
IGHV3-07 (SEQ ID NO:
77)/IGLV1-47 (SEQ ID NO:
167);
IGHV3-07 (SEQ ID NO:
77)/IGLV2-23 (SEQ ID NO:
174);
IGHV3-07 (SEQ ID NO:
77)/IGLV3-01 (SEQ ID NO:
175);
IGHV3-11 (SEQ ID NO:
79)/IGKV1-05 (SEQ ID NO:
118);
IGHV3-11 (SEQ ID NO:
79)/IGKV1-06 (SEQ ID NO:
119);
IGHV3-11 (SEQ ID NO:
79)/IGKV1-12 (SEQ ID NO:
122);
IGHV3-11 (SEQ ID NO:
79)/IGKV1-16 (SEQ ID NO:
124);
IGHV3-11 (SEQ ID NO:
79)/IGKV3-15 (SEQ ID NO:
153);
IGHV3-11 (SEQ ID NO:
79)/IGLV1-47 (SEQ ID NO:
167);
IGHV3-11 (SEQ ID NO:
79)/IGLV2-23 (SEQ ID NO:
174);
IGHV3-15 (SEQ ID NO:
81)/IGKV1-05 (SEQ ID NO:
118);
IGHV3-15 (SEQ ID NO:
81)/IGKV1-06 (SEQ ID NO:
119);
IGHV3-15 (SEQ ID NO:
81)/IGKV1-09 (SEQ ID NO:
121);
IGHV3-15 (SEQ ID NO:
81)/IGKV1-12 (SEQ ID NO:
122);
IGHV3-15 (SEQ ID NO:
81)/IGKV1-16 (SEQ ID NO:
124);
IGHV3-15 (SEQ ID NO:
81)/IGKV1-27 (SEQ ID NO:
126);
IGHV3-15 (SEQ ID NO:
81)/IGKV1-39 (SEQ ID NO:
129);
IGHV3-15 (SEQ ID NO:
81)/IGKV3-15 (SEQ ID NO:
153);
IGHV3-15 (SEQ ID NO:
81)/IGLV1-40 (SEQ ID NO:
165);
IGHV3-15 (SEQ ID NO:
81)/IGLV1-51 (SEQ ID NO:
169);
IGHV3-15 (SEQ ID NO:
81)/IGLV2-11 (SEQ ID NO:
171);
IGHV3-21 (SEQ ID NO:
84)/IGKV1-06 (SEQ ID NO:
119);
IGHV3-21 (SEQ ID NO:
84)/IGKV1-12 (SEQ ID NO:
122);
IGHV3-21 (SEQ ID NO:
84)/IGKV1-27 (SEQ ID NO:
126);
IGHV3-21 (SEQ ID NO:
84)/IGKV1-39 (SEQ ID NO:
129);
IGHV3-21 (SEQ ID NO:
84)/IGLV2-14 (SEQ ID NO:
172);
IGHV3-21 (SEQ ID NO:
84)/IGLV2-23 (SEQ ID NO:
174);
IGHV3-30 (SEQ ID NO:
86)/IGLV2-23 (SEQ ID NO:
174);
IGHV3-30 (SEQ ID NO:
86)/IGLV3-1 (SEQ ID NO:
175);
IGHV3-33 (SEQ ID NO:
89)/IGKV3-15 (SEQ ID NO:
153);
IGHV3-33 (SEQ ID NO:
89)/IGLV2-23 (SEQ ID NO:
174);
IGHV3-48 (SEQ ID NO:
93)/IGKV1-27 (SEQ ID NO:
126);
IGHV3-53 (SEQ ID NO:
95)/IGKV1-09 (SEQ ID NO:
121);
IGHV3-53 (SEQ ID NO:
95)/IGKV1-12 (SEQ ID NO:
122);
IGHV3-53 (SEQ ID NO:
95)/IGLV1-51 (SEQ ID NO:
169);
IGHV3-53 (SEQ ID NO:
95)/IGLV2-23 (SEQ ID NO:
174);
IGHV3-53 (SEQ ID NO:
95)/IGLV3-1 (SEQ ID NO:
175);
IGHV3-74 (SEQ ID NO:
100)/IGKV1-06 (SEQ ID NO:
119);
IGHV3-74 (SEQ ID NO:
100)/IGKV1-09 (SEQ ID NO:
121);
IGHV3-74 (SEQ ID NO:
100)/IGKV1-27 (SEQ ID NO:
126);
IGHV3-74 (SEO ID NO:
100)/IGKV3-15 (SEQ ID NO:
153);
IGHV3-74 (SEQ ID NO:
100)/IGLV1-51 (SEQ ID NO:
169);
IGHV4-04 (SEQ ID NO:
102)/IGLV2-23 (SEQ ID NO:
174);
IGHV4-04 (SEQ ID NO:
102)/IGLV3-1 (SEQ ID NO:
175);
IGHV4-04 (SEQ ID NO:
102)/IGLV3-21 (SEQ ID NO:
182);
IGHV4-39 (SEQ ID NO:
109)/IGLV2-14 (SEQ ID NO:
172);
IGHV4-39 (SEQ ID NO:
109)/IGLV3-1 (SEQ ID NO:
175);
IGHV5-51 (SEQ ID NO:113)/IGKV1-09 (SEQ ID NO:
121);
IGHV5-51 (SEQ ID NO:
113)/IGLV2-23 (SEQ ID NO:
174);
IGHV5-51 (SEQ ID NO:
113)/IGLV3-1 (SEQ ID NO:
175);
IGHV6-1 (SEQ ID NO:115)/IGKV1-06 (SEQ ID NO:
119);
and
IGHV6-1 (SEQ ID NO:
115)/IGLV2-23 (SEQ ID NO:
174).

191 more elements

Facts

Application

15/449,561Filed 3 Mar 2017 · division

Priority

EP 0916272429 May 2009

Published

US 2017/0218048 A13 Aug 2017

Granted

12 May 2020

Term ends

Not estimatedThe source records don’t support an estimate.

Classification15 codes

C07K 16/005
Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies: constructed by phage libraries
C07K 16/00
Immunoglobulins [ig]
C07K 16/32
Against material from animals or humans: against translation products of oncogenes
C12N 15/1093
Isolating an individual clone by screening libraries: general methods of preparing gene libraries, not provided for in other subgroups

Family

Application61/182,350Us provisional application · filed 29 May 2009

Application61/299,401Us provisional application · filed 29 Jan 2010

PCT/EP2010/057507Parent of this division · filed 29 May 2010

Application14/169,162Parent of this division · filed 31 Jan 2014

US 8,685,896 B2Parent of this division · filed 1 Apr 2014

US 2017/0218048 A1Pre-grant publication · published 3 Aug 2017

US 9,624,293 B2Parent of this division

Application13/321,564Parent of this division

US 2012/0077713 A1Published application

US 2014/0163208 A1Published application

US 10,647,757 B2This patent

From the US filing history. Foreign family members aren’t listed.