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US 2012/0230981 A1Published application
CH2 Domain Template Molecules Derived From Rational Grafting Of Donor Loops Onto CH2 Scaffolds
AssigneeResearch Corporation Technologies, Inc.
InventorsDavid Bramhill, Gopalan Raghunathan
Life of this patent
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Abstract
Novel CH2 domain template molecules wherein donor loops from a database of domains are transferred to a CH2 domain scaffold. At least one or up to three loops from a donor are transferred to the CH2 domain. The donor loops may be chosen based on length, e.g., the donor loop may have a length that is similar to that of a structural loop in the CH2 domain scaffold.
Claims98
A CH2 domain template molecule comprising a CH2 domain scaffold of IgG, IgA, IgD, or a CH3 domain scaffold of IgE, or IgM, having a L1 loop, a L2 loop, and a L3 loop;
- wherein:
- (a) the L1 loop is replaced with a donor L1 loop of a donor molecule, the donor molecule further comprising a donor L2 loop and a donor L3 loop, and the donor L2 loop of the donor molecule has a first length and the donor L3 loop of the donor molecule has a second length, the first length closely matching a length of the L2 loop of the CH2 domain scaffold and the second length closely matching a length of the L3 loop of the CH2 domain scaffold;
- or
- (b) the L2 loop is replaced with a donor L2 loop of a donor molecule, the donor molecule further comprising a donor L1 loop and a donor L3 loop, and the donor L1 loop of the donor molecule has a first length and the donor L3 loop of the donor molecule has a second length, the first length closely matching a length of the L1 loop of the CH2 domain scaffold and the second length closely matching a length of the L3 loop of the CH2 domain scaffold;
- or
- (c) the L3 loop is replaced with a donor L3 loop of a donor molecule, the donor molecule further comprising a donor L1 loop and a donor L2 loop, and the donor L1 loop of the donor molecule has a first length and the donor L2 loop of the donor molecule has a second length, the first length closely matching a length of the L1 loop of the CH2 domain scaffold and the second length closely matching a length of the L2 loop of the CH2 domain scaffold;
- or
- (d) the L1 loop and the L3 loop are replaced with either (i) a donor L1 loop and a donor L3 loop of a donor molecule, respectively, or (ii) the donor L3 loop and the donor L1 loop of the donor molecule, respectively;
- and the donor molecule further comprises a donor L2 loop having a first length, the first length closely matching a length of the L2 loop of the CH2 domain scaffold.
6 more elements
A CH2 domain template molecule comprising a CH2 domain scaffold of IgG, IgA, IgD, or a CH3 domain scaffold of IgE, or IgM, having a L1 loop, a L2 loop, and a L3 loop;
- wherein the L1 loop is replaced with a donor L1 loop of a donor molecule, the donor molecule further comprising a donor L2 loop and a donor L3 loop,
- wherein the donor L2 loop of the donor molecule has a first length and the donor L3 loop of the donor molecule has a second length, the first length closely matching a length of the L2 loop of the CH2 domain scaffold and the second length closely matching a length of the L3 loop of the CH2 domain scaffold.
A CH2 domain template molecule comprising a CH2 domain scaffold of IgG, IgA, IgD, or a CH3 domain scaffold of IgE, or IgM, having a L1 loop, a L2 loop, and a L3 loop;
- wherein the L2 loop is replaced with a donor L2 loop of a donor molecule, the donor molecule further comprising a donor L1 loop and a donor L3 loop,
- wherein the donor L1 loop of the donor molecule has a first length and the donor L3 loop of the donor molecule has a second length, the first length closely matching a length of the L1 loop of the CH2 domain scaffold and the second length closely matching a length of the L3 loop of the CH2 domain scaffold.
A CH2 domain template molecule comprising a CH2 domain scaffold of IgG, IgA, IgD, or a CH3 domain scaffold of IgE, or IgM, having a L1 loop, a L2 loop, and a L3 loop;
- wherein the L3 loop is replaced with a donor L3 loop of a donor molecule, the donor molecule further comprising a donor L1 loop and a donor L2 loop,
- wherein the donor L1 loop of the donor molecule has a first length and the donor L2 loop of the donor molecule has a second length, the first length closely matching a length of the L1 loop of the CH2 domain scaffold and the second length closely matching a length of the L2 loop of the CH2 domain scaffold.
A CH2 domain template molecule comprising a CH2 domain scaffold of IgG, IgA, IgD, or a CH3 domain scaffold of IgE, or IgM, having a L1 loop, a L2 loop, and a L3 loop;
- wherein the L1 loop and the L3 loop are replaced with either (i) a donor L1 loop and a donor L3 loop of a donor molecule, respectively, or (ii) the donor L3 loop and the donor L1 loop of the donor molecule, respectively;
- wherein the donor molecule further comprises a donor L2 loop having a first length, the first length closely matching a length of the L2 loop of the CH2 domain scaffold.
A CH2 domain template molecule comprising a first portion and a second portion, the first portion and the second portion being either:
- (i) a CH2 domain scaffold of IgG, IgA, IgD, or a CH3 domain scaffold of IgE, or IgM, having a L1 loop, a L2 loop, and a L3 loop, wherein the L1 loop is replaced with a donor L1 loop of a donor molecule, the donor molecule further comprising a donor L2 loop and a donor L3 loop, wherein the donor L2 loop of the donor molecule has a first length and the donor L3 loop of the donor molecule has a second length, the first length closely matching a length of the L2 loop of the CH2 domain scaffold and the second length closely matching a length of the L3 loop of the CH2 domain scaffold;
- (ii) a CH2 domain scaffold of IgG, IgA, IgD, or a CH3 domain scaffold of IgE, or IgM, having a L1 loop, a L2 loop, and a L3 loop, wherein the L2 loop is replaced with a donor L2 loop of a donor molecule, the donor molecule further comprising a donor L1 loop and a donor L3 loop, wherein the donor L1 loop of the donor molecule has a first length and the donor L3 loop of the donor molecule has a second length, the first length closely matching a length of the L1 loop of the CH2 domain scaffold and the second length closely matching a length of the L3 loop of the CH2 domain scaffold;
- (iii) a CH2 domain scaffold of IgG, IgA, IgD, or a CH3 domain scaffold of IgE, or IgM, having a L1 loop, a L2 loop, and a L3 loop, wherein the L3 loop is replaced with a donor L3 loop of a donor molecule, the donor molecule further comprising a donor L1 loop and a donor L2 loop, wherein the donor L1 loop of the donor molecule has a first length and the donor L2 loop of the donor molecule has a second length, the first length closely matching a length of the L1 loop of the CH2 domain scaffold and the second length closely matching a length of the L2 loop of the CH2 domain scaffold;
- (iv) a CH2 domain scaffold of IgG, IgA, IgD, or a CH3 domain scaffold of IgE, or IgM, having a L1 loop, a L2 loop, and a L3 loop, wherein the L1 loop and the L2 loop are replaced with either (a) a donor L1 loop and a donor L2 loop of a donor molecule, respectively, or (b) the donor L2 loop and the donor L1 loop of the donor molecule, respectively, wherein the donor molecule further comprises a donor L3 loop having a first length, the first length closely matching a length of the L3 loop of the CH2 domain scaffold;
- (v) a CH2 domain scaffold of IgG, IgA, IgD, or a CH3 domain scaffold of IgE, or IgM, having a L1 loop, a L2 loop, and a L3 loop, wherein the L1 loop and the L3 loop are replaced with either (a) a donor L1 loop and a donor L3 loop of a donor molecule, respectively, or (b) the donor L3 loop and the donor L1 loop of the donor molecule, respectively, wherein the donor molecule further comprises a donor L2 loop having a first length, the first length closely matching a length of the L2 loop of the CH2 domain scaffold;
- (vi) a CH2 domain scaffold of IgG, IgA, IgD, or a CH3 domain scaffold of IgE, or IgM, having a L1 loop, a L2 loop, and a L3 loop, wherein the L2 loop and the L3 loop are replaced with either (a) a donor L2 loop and a donor L3 loop of a donor molecule, respectively, or (b) the donor L3 loop and the donor L2 loop of the donor molecule, respectively, wherein the donor molecule further comprises a donor L1 loop having a first length, the first length closely matching a length of the L1 loop of the CH2 domain scaffold;
- or
- (vii) a CH2 domain scaffold of IgG, IgA, IgD, or a CH3 domain scaffold of IgE, or IgM, having a L1 loop, a L2 loop, and a L3 loop, wherein the L1 loop, the L2 loop, and the L3 loop are replaced with any of (a) a donor L1 loop, a donor L2 loop, and a donor L3 loop of a donor molecule, respectively;
- (b) a donor L1 loop, a donor L3 loop, and a donor L2 loop of a donor molecule, respectively;
- (c) a donor L2 loop, a donor L1 loop, and a donor L3 loop of a donor molecule, respectively;
- (d) a donor L2 loop, a donor L3 loop, and a donor L1 loop of a donor molecule, respectively;
- (e) a donor L3 loop, a donor L1 loop, and a donor L2 loop of a donor molecule, respectively;
- or (f) a donor L3 loop, a donor L2 loop, and a donor L1 loop of a donor molecule, respectively;
- the donor molecule comprising a donor L1 loop, a donor L2 loop, and a donor L3 loop.
11 more elements
A method of identifying a CH2 domain template molecule that specifically binds a target, the method comprises:
- (a) providing a library of particles displaying on their surface a CH2 domain template molecule comprising either:
- (i) a CH2 domain scaffold of IgG, IgA, IgD, or a CH3 domain scaffold of IgE, or IgM, having a L1 loop, a L2 loop, and a L3 loop, wherein the L1 loop is replaced with a donor L1 loop of a donor molecule, the donor molecule further comprising a donor L2 loop and a donor L3 loop, wherein the donor L2 loop of the donor molecule has a first length and the donor L3 loop of the donor molecule has a second length, the first length closely matching a length of the L2 loop of the CH2 domain scaffold and the second length closely matching a length of the L3 loop of the CH2 domain scaffold;
- (ii) a CH2 domain scaffold of IgG, IgA, IgD, or a CH3 domain scaffold of IgE, or IgM, having a L1 loop, a L2 loop, and a L3 loop, wherein the L2 loop is replaced with a donor L2 loop of a donor molecule, the donor molecule further comprising a donor L1 loop and a donor L3 loop, wherein the donor L1 loop of the donor molecule has a first length and the donor L3 loop of the donor molecule has a second length, the first length closely matching a length of the L1 loop of the CH2 domain scaffold and the second length closely matching a length of the L3 loop of the CH2 domain scaffold;
- (iii) a CH2 domain scaffold of IgG, IgA, IgD, or a CH3 domain scaffold of IgE, or IgM, having a L1 loop, a L2 loop, and a L3 loop, wherein the L3 loop is replaced with a donor L3 loop of a donor molecule, the donor molecule further comprising a donor L1 loop and a donor L2 loop, wherein the donor L1 loop of the donor molecule has a first length and the donor L2 loop of the donor molecule has a second length, the first length closely matching a length of the L1 loop of the CH2 domain scaffold and the second length closely matching a length of the L2 loop of the CH2 domain scaffold;
- (iv) a CH2 domain scaffold of IgG, IgA, IgD, or a CH3 domain scaffold of IgE, or IgM, having a L1 loop, a L2 loop, and a L3 loop, wherein the L1 loop and the L2 loop are replaced with either (a) a donor L1 loop and a donor L2 loop of a donor molecule, respectively, or (b) the donor L2 loop and the donor L1 loop of the donor molecule, respectively, wherein the donor molecule further comprises a donor L3 loop having a first length, the first length closely matching a length of the L3 loop of the CH2 domain scaffold;
- (v) a CH2 domain scaffold of IgG, IgA, IgD, or a CH3 domain scaffold of IgE, or IgM, having a L1 loop, a L2 loop, and a L3 loop, wherein the L1 loop and the L3 loop are replaced with either (a) a donor L1 loop and a donor L3 loop of a donor molecule, respectively, or (b) the donor L3 loop and the donor L1 loop of the donor molecule, respectively, wherein the donor molecule further comprises a donor L2 loop having a first length, the first length closely matching a length of the L2 loop of the CH2 domain scaffold;
- (vi) a CH2 domain scaffold of IgG, IgA, IgD, or a CH3 domain scaffold of IgE, or IgM, having a L1 loop, a L2 loop, and a L3 loop, wherein the L2 loop and the L3 loop are replaced with either (a) a donor L2 loop and a donor L3 loop of a donor molecule, respectively, or (b) the donor L3 loop and the donor L2 loop of the donor molecule, respectively, wherein the donor molecule further comprises a donor L1 loop having a first length, the first length closely matching a length of the L1 loop of the CH2 domain scaffold;
- or
- (vii) a CH2 domain scaffold of IgG, IgA, IgD, or a CH3 domain scaffold of IgE, or IgM, having a L1 loop, a L2 loop, and a L3 loop, wherein the L1 loop, the L2 loop, and the L3 loop are replaced with any of (a) a donor L1 loop, a donor L2 loop, and a donor L3 loop of a donor molecule, respectively;
- (b) a donor L1 loop, a donor L3 loop, and a donor L2 loop of a donor molecule, respectively;
- (c) a donor L2 loop, a donor L1 loop, and a donor L3 loop of a donor molecule, respectively;
- (d) a donor L2 loop, a donor L3 loop, and a donor L1 loop of a donor molecule, respectively;
- (e) a donor L3 loop, a donor L1 loop, and a donor L2 loop of a donor molecule, respectively;
- or (f) a donor L3 loop, a donor L2 loop, and a donor L1 loop of a donor molecule, respectively;
- the donor molecule comprising a donor L1 loop, a donor L2 loop, and a donor L3 loop;
- (b) introducing the target to the library of particles;
- and
- (c) selecting particles from the library that specifically bind to the target.
15 more elements
Dependencies are inferred from the claim text.