# US 11,305,020 B2 · Methods for reducing toxicity of a chemotherapeutic drug

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- Number: US 11,305,020 B2
- Document ID: US11305020B2
- Status: Granted
- Kind: B2
- Application number: 16/086,978
- Filed: 2017-03-21
- Published: 2019-04-04
- Granted: 2022-04-19
- Earliest claimed: 2016-03-21
- Assignees: Mayo Foundation for Medical Education and Research
- Applicants: Mayo Foundation for Medical Education and Research
- Inventors: Svetomir N. Markovic; Wendy K. Nevala
- Web page: https://patentgrep.com/patent/US11305020B2

## CPC

- A61K 47/643: {Albumins, e.g. HSA, BSA, ovalbumin or a Keyhole Limpet Hemocyanin [KHL]}
- A61K 31/337: having four-membered rings, e.g. taxol
- A61K 39/3955: {against proteinaceous materials, e.g. enzymes, hormones, lymphokines}
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61K 47/6867: {the tumour determinant being from a cell of a blood cancer}
- A61K 47/6929: {the form being a nanoparticle, e.g. an immuno-nanoparticle}
- A61P 35/00: Antineoplastic agents
- C07K 16/22: against growth factors {; against growth regulators}
- C07K 16/244: {Interleukins [IL]}
- C07K 16/249: {Interferons}
- C07K 16/2806: {against CD2}
- C07K 16/2809: {against the T-cell receptor (TcR)-CD3 complex}
- C07K 16/2827: {against B7 molecules, e.g. CD80, CD86}
- C07K 16/2842: {against integrin beta1-subunit-containing molecules, e.g. CD29, CD49}
- C07K 16/2845: {against integrin beta2-subunit-containing molecules, e.g. CD11, CD18}
- C07K 16/2878: {against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95}
- C07K 16/2887: {against CD20}
- C07K 16/2893: {against CD52}
- C07K 16/3061: {Blood cells}
- C07K 16/4208: {against an idiotypic determinant on Ig}
- C07K 16/4291: {against IgE}
- A61K 9/0019: {Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00)}
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)

## Abstract

This disclosure relates to methods for improving the therapeutic index of a chemotherapeutic drug in the treatment of patients afflicted with cancer, by reducing chemotherapy-related toxicity to a level that allows the chemotherapeutic drug to be used in humans.

## Claims

### Claim 1

A method for providing an acceptable therapeutic index of a chemotherapeutic drug targeting cancer cells, which method comprises:
a) combining a therapeutically effective amount of said drug with a biocompatible protein carrier, wherein the drug has an unacceptable therapeutic index when administered alone;
b) forming a complex with said carrier and an effective amount of an anti-CD20 antibody which has specificity to a CD20 antigen on said cancer cells, wherein said anti-CD20 antibodies populate the surface of said complex and retain binding specificity; and
c) administering said complex to a patient, wherein said administration enhances delivery of said drug to said cells and reduces one or more side effects of said drug, thereby increasing the therapeutic index of said drug to provide an acceptable therapeutic index.

### Claim 2 (depends on 1)

The method of claim 1, wherein the protein carrier is selected from the group consisting of albumin, gelatin, elastin, gliadin, legumin, zein, soy protein, milk protein, and whey protein.

### Claim 3 (depends on 2)

The method of claim 2, wherein the protein carrier is albumin.

### Claim 4 (depends on 3)

The method of claim 3, wherein the complex further comprises an effective amount of paclitaxel to form said complex.

### Claim 5 (depends on 4)

The method of claim 4, wherein the amount of paclitaxel is between 0.1 mg/m2 and 50 mg/m2.

### Claim 6

A method for providing an acceptable therapeutic index of a chemotherapeutic drug targeting tumor cells, which method comprises:
a) combining a therapeutically effective amount of said drug with an albumin carrier, wherein the drug has an unacceptable therapeutic index when administered alone;
b) forming a complex with said carrier and an effective amount of an anti-CD20 antibody which has specificity to a CD20 antigen on said tumor cells, wherein said anti-CD20 antibodies populate the surface of said complex and retain binding specificity; and
c) administering said complex to a patient wherein said administration enhances delivery of said drug to said tumor cells and reduces one or more side effects of said drug, thereby increasing the therapeutic index of said drug.

### Claim 7 (depends on 6)

The method of claim 6, wherein the complex further comprises an effective amount of paclitaxel to form said complex.

### Claim 8 (depends on 7)

The method of claim 7, wherein the amount of paclitaxel is between 0.1 mg/m2 and 50 mg/m2.

### Claim 9 (depends on 1)

The method of claim 1, wherein said complex is less than 1 micron in diameter.

### Claim 10 (depends on 1)

The method of claim 1, wherein drug-related toxicity is reduced.

### Claim 11

A method for providing an acceptable therapeutic index of a chemotherapeutic drug targeting aberrant mammalian cells, which method comprises:
a) combining a therapeutically effective amount of said drug with a biocompatible protein carrier, wherein the drug has an unacceptable therapeutic index when administered alone;
b) forming a complex with said carrier and an effective amount of anti-CD20 antibody having specificity to said aberrant cells, wherein said anti-CD20 antibody populates the surface of said complex and retains specificity and further wherein said anti-CD20 antibody has a protein carrier-binding portion; and
c) administering said complex to a patient, wherein said administration enhances delivery of said drug to said cells and reduces one or more side effects of said drug, thereby increasing the therapeutic index of said drug.

### Claim 12 (depends on 11)

The method of claim 11, wherein the aberrant mammalian cells are selected from the group consisting of cancer cells, autoimmune disease-related cells, inflammatory disease-related cells, virus-infected cells, and bacteria-infected cells.

### Claim 13 (depends on 11)

The method of claim 11, wherein the protein carrier is selected from the group consisting of albumin, gelatin, elastin, gliadin, legumin, zein, soy protein, milk protein, and whey protein.

### Claim 14 (depends on 12)

The method of claim 12, wherein the protein carrier is albumin.

### Claim 15 (depends on 13)

The method of claim 13, wherein the complex further comprises an effective amount of paclitaxel to form said complex.

### Claim 16 (depends on 14)

The method of claim 14, wherein the amount of paclitaxel is between 0.1 mg/m2 and 50 mg/m2.