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NZ781602B2 - Trispecific and/or trivalent binding proteins for prevention or treatment of HIV infection - Google Patents
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NZ781602B2 - Trispecific and/or trivalent binding proteins for prevention or treatment of HIV infection - Google Patents

Trispecific and/or trivalent binding proteins for prevention or treatment of HIV infection

Info

Publication number
NZ781602B2
NZ781602B2 NZ781602A NZ78160216A NZ781602B2 NZ 781602 B2 NZ781602 B2 NZ 781602B2 NZ 781602 A NZ781602 A NZ 781602A NZ 78160216 A NZ78160216 A NZ 78160216A NZ 781602 B2 NZ781602 B2 NZ 781602B2
Authority
NZ
New Zealand
Prior art keywords
sequence
seq
amino acid
binding protein
cdr
Prior art date
Application number
NZ781602A
Other versions
NZ781602A (en
Inventor
Mangaiarkarasi Asokan
Christian Beil
Jochen Beninga
Mark Connors
Rose Nicole A Doria
Jinghe Huang
Richard A Koup
Jochen Kruip
Young Do Kwon
Peter D Kwong
Original Assignee
Sanofi
The Usa As Represented By The Secretary Department Of Health And Human Services
Filing date
Publication date
Application filed by Sanofi, The Usa As Represented By The Secretary Department Of Health And Human Services filed Critical Sanofi
Publication of NZ781602A publication Critical patent/NZ781602A/en
Publication of NZ781602B2 publication Critical patent/NZ781602B2/en

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A61K39/42—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum viral
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • A61K47/6835—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment the modifying agent being an antibody or an immunoglobulin bearing at least one antigen-binding site
    • A61K47/6881—Cluster-antibody conjugates, i.e. the modifying agent consists of a plurality of antibodies covalently linked to each other or of different antigen-binding fragments covalently linked to each other
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A61P31/18—Antivirals for RNA viruses for HIV
    • C07K16/1063—
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/46—Hybrid immunoglobulins
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/46—Hybrid immunoglobulins
    • C07K16/468—Immunoglobulins having two or more different antigen binding sites, e.g. multifunctional antibodies
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/31—Immunoglobulins specific features characterized by aspects of specificity or valency multispecific
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
    • C07K2317/565—Complementarity determining region [CDR]
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
    • C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
    • C07K2317/94—Stability, e.g. half-life, pH, temperature or enzyme-resistance

Abstract

Provided herein are compositions comprising trispecific and/or trivalent binding proteins comprising four polypeptide chains that form three antigen binding sites that specifically bind one or more HIV target proteins or one or more T-cell receptors, wherein a first pair of polypeptides forming the binding protein possess dual variable domains having a cross-over orientation and wherein a second pair of polypeptides forming the binding protein possess a single variable domain. Also provided herein are methods for making trispecific and/or trivalent binding proteins and uses of such binding proteins for the treatment and/or prevention of HIV/AIDS.

Claims (11)

1. A binding protein comprising four polypeptide chains that form three antigen binding sites, wherein a first polypeptide chain comprises a structure represented by the formula: V - L -V - L -C [I] L2 1 L1 2 L and a second polypeptide chain comprises a structure represented by the formula: V - L -V - L -C -hinge-C -C [II] H1 3 H2 4 H1 H2 H3 and a third polypeptide chain comprises a structure represented by the formula: V -C -hinge-C -C [III] H3 H1 H2 H3 and a fourth polypeptide chain comprises a structure represented by the formula: V -C [IV] wherein: V is a first immunoglobulin light chain variable domain; V is a second immunoglobulin light chain variable domain; V is a third immunoglobulin light chain variable domain; V is a first immunoglobulin heavy chain variable domain; V is a second immunoglobulin heavy chain variable domain; V is a third immunoglobulin heavy chain variable domain; C is an immunoglobulin light chain constant domain; C is an immunoglobulin C heavy chain constant domain; H1 H1 C is an immunoglobulin C heavy chain constant domain; H2 H2 C is an immunoglobulin C heavy chain constant domain; H3 H3 hinge is an immunoglobulin hinge region connecting the C and C domains; and H1 H2 L , L , L and L are amino acid linkers; 1 2 3 4 and wherein the polypeptide of formula I and the polypeptide of formula II form a cross-over light chain-heavy chain pair; and wherein: VL1 and VH1 form a first antigen binding site that specifically binds glycoprotein 41, wherein V comprises a light chain variable domain comprising the sequence of SEQ ID NO: 518, and wherein V comprises a heavy chain variable domain comprising the sequence of SEQ ID NO: 504; 21791445_1 (GHMatters) P44041NZ01 V and V form a second antigen binding site that specifically binds glycoprotein L2 H2 120, wherein V comprises a CDR-L1 comprising the sequence of SEQ ID NO: 275, a CDR-L2 comprising the sequence of SEQ ID NO: 276, and a CDR-L3 comprising the sequence of SEQ ID NO: 277, and wherein V comprises a CDR-H1 comprising the sequence of SEQ ID NO: 257, a CDR-H2 comprising the sequence of SEQ ID NO: 258, and a CDR-H3 comprising the sequence of SEQ ID NO: 259; and V and V form a third antigen binding site that specifically binds glycoprotein L3 H3 120, wherein V comprises a CDR-L1 comprising the sequence of SEQ ID NO: 266, a CDR-L2 comprising the sequence of SEQ ID NO: 267, and a CDR-L3 comprising the sequence of SEQ ID NO: 268, and wherein V comprises a CDR-H1 comprising the sequence of SEQ ID NO: 248, a CDR-H2 comprising the sequence of SEQ ID NO: 497, and a CDR-H3 comprising the sequence of SEQ ID NO: 250.
2. The binding protein of claim 1, wherein V comprises a light chain variable domain comprising the sequence of SEQ ID NO: 519 and V comprises a heavy chain variable domain comprising the sequence of SEQ ID NO: 506.
3. The binding protein of claim 1 or 2, wherein the first polypeptide chain comprises the amino acid sequence of SEQ ID NO:4 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:4 and the second polypeptide chain comprises the amino acid sequence of SEQ ID NO:3 or an amino acid sequence that is at least 95% identical to the amino acid sequence of SEQ ID NO:3.
4. The binding protein of claim 1 or 2, wherein: (a) the C domain of the second polypeptide chain comprises amino acid substitutions at positions corresponding to positions 354 and 366 of human IgG1 according to EU Index, wherein the amino acid substitutions are S354C and T366W; and wherein the C domain of the third polypeptide chain comprises amino acid substitutions at positions corresponding to positions 349, 366, 368, and 407 of human IgG1 according to EU Index, wherein the amino acid substitutions are Y349C, T366S, L368A, and Y407V; or (b) the CH3 domain of the second polypeptide chain comprises amino acid substitutions at positions corresponding to positions 349, 366, 368, and 407 of human IgG1 according to EU Index, wherein the amino acid substitutions are Y349C, T366S, L368A, and Y407V; and wherein the C domain of the third polypeptide chain comprises amino acid 21791445_1 (GHMatters) P44041NZ01 substitutions at positions corresponding to positions 354 and 366 of human IgG1 according to EU Index, wherein the amino acid substitutions are S354C and T366W.
5. The binding protein of any one of claims 1, 2, and 4, wherein the C domains of the second and the third polypeptide chains both comprise amino acid substitutions at positions corresponding to positions 428 and 434 of human IgG1 according to EU Index, wherein the amino acid substitutions are M428L and N434S.
6. The binding protein of any one of claims 1, 2, 4, and 5, wherein: (a) at least one of L , L , L , or L is independently 0 amino acids in length; or 1 2 3 4 (b) L , L , L , or L are each independently at least one amino acid in length. 1 2 3 4
7. The binding protein of any one of claims 1, 2, 4, 5, and 6, wherein: (a) L , L , L , and/or L comprise the sequence Asp-Lys-Thr-His-Thr (SEQ ID NO: 1 2 3 4 525); or (b) L , L , L , and/or L comprise the sequence Gly-Gln-Pro-Lys-Ala-Ala-Pro (SEQ 1 2 3 4 ID NO: 299).
8. An isolated nucleic acid molecule comprising a nucleotide sequence encoding the binding protein of any one of claims 1-7.
9. An expression vector comprising the nucleic acid molecule of claim 8.
10. A vector system comprising one or more vectors encoding a first, second, third, and fourth polypeptide chain of a binding protein of any one of claims 1-7, wherein optionally: (a) the vector system comprises a first vector encoding the first polypeptide chain of the binding protein, a second vector encoding the second polypeptide chain of the binding protein, a third vector encoding the third polypeptide chain of the binding protein, and a fourth vector encoding the fourth polypeptide chain of the binding protein or (b) the vector system comprises a first vector encoding the first and second polypeptide chains of the binding protein, and a second vector encoding the third and fourth polypeptide chains of the binding protein.
11. An isolated host cell comprising the nucleic acid molecule of claim 8, the expression vector of claim 9, or the vector system of claim 10, wherein optionally the host cell is a 21791445_1 (GHMatters) P44041NZ01
NZ781602A 2016-10-24 Trispecific and/or trivalent binding proteins for prevention or treatment of HIV infection NZ781602B2 (en)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US201562246113P 2015-10-25 2015-10-25
EP16305211 2016-02-24
US201662322029P 2016-04-13 2016-04-13
US201662331169P 2016-05-03 2016-05-03
NZ742825A NZ742825B2 (en) 2016-10-24 Trispecific and/or trivalent binding proteins for prevention or treatment of hiv infection

Publications (2)

Publication Number Publication Date
NZ781602A NZ781602A (en) 2025-07-25
NZ781602B2 true NZ781602B2 (en) 2025-10-29

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