Substantially homogeneous bio-affecting material having a pre-determined ratio of bioaffecting component to cell targeting component, the method for making such a material and the method of its use
OwnerW. Page Faulkinventor
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Abstract
A homogeneous conjugate for targeting and treating diseased cells wherein the conjugate has a predetermined ratio of drug molecules to protein molecules that preferentially bind to such cells and a method for making such a conjugate. The method of making the conjugate comprises adding drug molecules to linker molecules in a manner that effectively results in one molecule of drug for each molecule of linker followed by the addition of the drug-linker combination to protein molecules in order to achieve the predetermined ratio of drug molecules to protein molecules.
Claims41
A method for making a transferrin-doxorubicin conjugate having a predetermined ratio of doxorubicin to transferrin comprising the steps of:
- a) adding the doxorubicin to a glutaraldehyde linker material in a manner that effectively results in the addition of each doxorubicin molecule to one glutaraldehyde molecule;
- and
- b) adding the doxorubicin/glutaraldehyde combination to transferrin in a manner that results in a conjugate predetermined ratio of transferrin to doxorubicin;
- wherein said transferrin-doxorubicin conjugate is substantially free of diners, trimers and aggregates.
A method for making a conjugate having a predetermined drug:
- protein ratio, comprising
- a) adding a solution of a drug dropwise to a molar excess of a linker molecule solution to link each drug molecule to one linker molecule in a drug/linker combination;
- and
- b) adding the drug/linker combination to a protein targeting agent to produce a conjugate having the predetermined drug:
- protein ratio,
- wherein said conjugate is substantially free of dimers, trimers and aggregates.
A substantially homogeneous material comprising a protein conjugated with a bioaffecting molecule in a predetermined ratio of bio-affecting molecules to protein molecules, wherein said protein is attracted to receptors on target cells.
A homogeneous monomeric material suitable for bio-affecting target cells, said material consisting essentially of a monomeric conjugate, said monomeric conjugate comprising a protein that is attachable to receptors found in abundance on the target cells and a bio-affecting active molecule in a predetermined ratio of the bio-affecting active molecule to the protein, wherein said material is substantially free of dimers, trimers and aggregates.
A reagent kit for the treatment of tumors, comprising iron-bearing transferrin, and a homogeneous conjugate with a predetermined and consistent number of antitumor agent molecules per molecule of transferrin.
A reagent kit for determining the susceptibility of tumor cells to anti-tumor agents, comprising two or more homogeneous conjugates with a predetermined and consistent number of antitumor agent molecules per molecule of transferrin, wherein said homogeneous conjugates have different antitumor agents.
A method for making a conjugate having a predetermined drug:
- protein ratio, comprising
- a) adding a solution of a linker molecule drop-wise to solution of a cryopreservative to produce a first intermediate product,
- b) adding a solution of a drug dropwise to a molar excess of said first intermediate product to link each drug molecule to one linker molecule in a drug/linker combination to produce a second intermediate product;
- and
- c) adding the second intermediate product to a protein targeting agent to produce a third intermediate product having the predetermined drug:
- protein ratio,
- d) adding a linker scavenging agent to said third intermediate product to produce a fourth intermediate product, and
- e) filtering said fourth intermediate product to obtain a conjugate having a predetermined drug:
- protein ratio,
- wherein said conjugate is substantially free of dimers, trimers and aggregates.
Dependencies are inferred from the claim text.