Method of catalyzing chemical reactions
AssigneeIgen, Inc.
InventorsGerald Schochetman, Richard J. Massey
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Abstract
A method for increasing the rate of chemical reactions involving the conversion of at least one reactant to at least one product involves contacting the reactant with an appropriate monoclonal antibody under conditions permitting the formation of a complex between the antibody and the reactant. The complexed reactant is converted to the product which is then released from the complex. The monoclonal antibody may employ a cofactor and may be directed to a known substrate of an enzyme. Methods for preparing such monoclonal antibodies are also disclosed.
Claims27
A method for catalyzing a chemical reaction wherein at least one reactant is converted to at least one product comprising the step of:
- contacting the reactant with at least one monoclonal antibody capable of catalytically increasing the rate of conversion of reactant to product in said chemical reaction, said contact being performed under conditions wherein a complex is formed between said monoclonal antibody and said reactant, the said reactant is catalytically converted to said product, and the said product is released from said complex, said monoclonal antibody having been produced by a process comprising the steps of:
- (a) generating a plurality of monoclonal antibodies to an antigen selected from the group consisting of:
- (i) the reactant,
- (ii) the reactant bound to a peptide of other carrier molecule,
- (iii) a reaction intermediate,
- (iv) an analog of the reactant,
- (v) an analog of the product in which the monoclonal antibody so generated is capable of binding to the reactant or a reaction intermediate, and
- (vi) an analog of a reaction intermediate, and
- (b) screening said plurality of monoclonal antibodies to identify a monoclonal antibody which catalyzes the reaction.
A method for catalyzing a chemical reaction wherein at least one reactant is converted to at least one product comprising the step of:
- contacting the reactant with at least one monoclonal antibody capable of catalytically increasing the rate of conversion of reactant to product in said chemical reaction, said contact being performed under conditions wherein a complex is formed between said monoclonal antibody and said reactant, the said reactant is catalytically converted to said product, and the said product is released from said complex, said monoclonal antibody being characterized by a K>1, where K=k.sub.r /k.sub.p, K.sub.r is the affinity constant of the monoclonal antibody for the product, and wherein said chemical reaction is characterized by an r.sub.1 >r.sub.o, where r.sub.1 is the rate of formation of the complex between the antibody and the reactant and where r.sub.o is the rate of the chemical reaction in the absence of monoclonal antibody, by an r.sub.2 >r.sub.o, where r.sub.2 is the rate of the conversion of the complexed reactant to the complexed product and by a r.sub.3 >r.sub.o, where r.sub.3 is the rate of release of the product from the complex, said monoclonal antibody having been produced by a process comprising the steps of:
- (a) generating a plurality of monoclonal antibodies to an antigen selected from the group consisting of:
- (i) the reactant,
- (ii) the reactant bound to a peptide or other carrier molecule,
- (iii) a reaction intermediate,
- (iv) an analog of the reactant,
- (v) an analog of the product in which the monoclonal antibody so generated is capable of binding to the reactant or a reaction intermediate, and
- (vi) an analog of a reaction intermediate, and
- (b) screening said plurality of monoclonal antibodies to identify a monoclonal antibody which catalyzes the reaction.
A method for catalyzing a chemical reaction wherein at least one reactant is converted to at least one product comprising the step of:
- contacting the reactant with at least one monoclonal antibody capable of catalytically increasing the rate of conversion of reactant to product in said chemical reaction, said contact being performed under conditions wherein a complex is formed between said monoclonal antibody and said reactant, the said reactant is catalytically converted to said product, and the said product is released from said complex, said monoclonal antibody having been produced by a process comprising the steps of:
- (a) immunizing an animal with an analog of the reactant, and thereby generating antibody-producing lymphocytes is said animal;
- (b) removing said antibody-producing lymphocytes from said animal;
- (c) fusing said antibody-producing lymphocytes with myeloma cells and thereby producing a plurality of hybridoma cells each producing monoclonal antibodies;
- (d) screening said plurality of monoclonal antibodies to identify a monoclonal antibody which catalyzes the desired reaction;
- and
- (e) producing a quantity of the monoclonal antibody identified in step (d) by culturing a plurality of hybridoma cells, each of which produces said monoclonal antibody.
A method for catalyzing a chemical reaction which is known to be catalyzed by an enzyme and wherein at least one reactant is converted to at least one product comprising the step of:
- contacting the reactant with at least one monoclonal antibody capable of catalytically increasing the rate of conversion of reactant to product in said chemical reaction, said contact being performed under conditions wherein a complex is formed between said monoclonal antibody and said reactant, the said reactant is catalytically converted to said product, and the said product is released from said complex, said monoclonal antibody having been prepared by a process comprising the steps of:
- (a) generating a plurality of monoclonal antibodies to said enzyme;
- (b) screening said plurality of monoclonal antibodies to identify a first monoclonal antibody which inhibits binding of the reactant to the enzyme;
- (c) recovering the said first monoclonal antibody;
- (d) generating a plurality of anti-idiotype monoclonal antibodies to the said first antibody recovered in step (c);
- (e) screening said plurality of anti-idiotype monoclonal antibodies generated in step (d) to identify a second monoclonal antibody which binds the reactant and catalyzes the desired reaction;
- and
- (f) producing a quantity of the monoclonal antibody identified in step (e) by culturing a plurality of hybridoma cells, each of which produces said monoclonal antibody.
Dependencies are inferred from the claim text.