# US 9,446,148 B2 · Carrier-antibody compositions and methods of making and using the same

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- Number: US 9,446,148 B2
- Document ID: US9446148B2
- Status: Granted
- Kind: B2
- Application number: 14/882,327
- Filed: 2015-10-13
- Published: 2016-04-07
- Granted: 2016-09-20
- Earliest claimed: 2014-10-06
- 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/US9446148B2

## CPC

- C07K 16/22: against growth factors {; against growth regulators}
- A61K 9/0095: {Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches (A61K9/0007 takes precedence; eatable gels or foams A61K9/0056; oral mucosa adhesive forms A61K9/006)}
- A61K 9/08: Solutions {(composition of solutions A61K47/00)}
- A61K 9/146: {with organic macromolecular compounds}
- A61K 9/1658: {Proteins, e.g. albumin, gelatin}
- A61K 9/19: lyophilised {, i.e. freeze-dried, solutions or dispersions (lyophilised products with subsequent particle size reduction A61K9/14; granules or pellets made by lyphilisation A61K9/1682; solid oral dosage forms made by lyophilisation A61K9/2095; lyophilisation additives A61K47/00)}
- A61K 31/337: having four-membered rings, e.g. taxol
- A61K 33/24: Heavy metals; Compounds thereof
- A61K 33/243: Platinum; Compounds thereof
- A61K 39/3955: {against proteinaceous materials, e.g. enzymes, hormones, lymphokines}
- A61K 39/39591: {Stabilisation, fragmentation}
- A61K 47/643: {Albumins, e.g. HSA, BSA, ovalbumin or a Keyhole Limpet Hemocyanin [KHL]}
- A61K 47/6845: {the antibody targeting a cytokine, e.g. growth factors, VEGF, TNF, a lymphokine or an interferon}
- A61K 47/6849: {the antibody targeting a receptor, a cell surface antigen or a cell surface determinant}
- A61K 47/6851: {the antibody targeting a determinant of a tumour cell}
- A61K 47/6871: {the antibody targeting an enzyme}
- A61K 47/6929: {the form being a nanoparticle, e.g. an immuno-nanoparticle}
- A61K 47/6931: {the material constituting the nanoparticle being a polymer}
- A61K 51/1021: {against cytokines, e.g. growth factors, VEGF, TNF, lymphokines or interferons}
- A61P 35/00: Antineoplastic agents
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07K 16/2863: {against receptors for growth factors, growth regulators}
- C07K 16/2887: {against CD20}
- C07K 16/30: from tumour cells
- C07K 16/32: against translation products of oncogenes
- C07K 16/40: against enzymes
- A61K 2039/505: {comprising antibodies}
- B82Y 5/00: Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- C07K 2317/52: Constant or Fc region; Isotype
- C07K 2317/73: Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- C07K 2317/92: Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
- 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)
- 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
- B82Y: SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES

## Abstract

Described herein are compositions of antibodies and carrier proteins and methods of making and using the same, in particular, as a cancer therapeutic. Also described are lyophilized compositions of antibodies and carrier proteins and methods of making and using the same, in particular, as a cancer therapeutic.

## Claims

### Claim 1

A lyophilized composition comprising nanoparticle complexes having an outer surface, wherein each of the nanoparticle complexes comprises:
albumin;
between about 100 to about 1000 bevacizumab antibodies, each having a hydrophobic Fc portion and a VEGF-binding portion, wherein the VEGF-binding portion is arranged on the outer surface of the complex; and
paclitaxel;
said nanoparticle complexes being lyophilized, and wherein upon reconstitution with an aqueous solution the VEGF-binding portions of said antibodies remain arranged on the outer surface of the complexes and remain capable of binding to VEGF in vivo and the Fc portions are associated with said albumin; and further wherein said complexes have an average size of from about 130 nm to about 800 nm.

### Claim 2 (depends on 1)

The lyophilized composition of claim 1 that is stable at about 20° C. to about 25° C. for at least 3 months.

### Claim 3 (depends on 1)

The lyophilized composition of claim 1, wherein each of the nanoparticle complexes comprises between about 400 and about 800 antibodies.

### Claim 4 (depends on 3)

The lyophilized composition of claim 3, wherein less than 0.01% of nanoparticles in the composition have a size greater than 800 nm.

### Claim 5 (depends on 1)

The lyophilized composition of claim 1, wherein the average size of said complexes in the composition is from greater than 800 nm to about 3.5 μm.

### Claim 6 (depends on 1)

The lyophilized composition of claim 1 wherein said nanoparticles complexes have an average size of approximately 160 nm.

### Claim 7 (depends on 1)

The lyophilized composition of claim 1, wherein the paclitaxel is located inside the nanoparticle complexes, arranged on the outside surface of the nanoparticle complexes, or both.

### Claim 8 (depends on 1)

The composition of claim 1, wherein the albumin is human serum albumin.

### Claim 9 (depends on 1)

The composition of claim 1, wherein the antibodies arrange into a substantially single layer of antibodies on all or part of the surface of the complexes.

### Claim 10 (depends on 1)

The composition of claim 1, wherein the complexes have an average size of approximately 160 nm and a dissociation constant between about 1×10−11 M and about 1×10−9 M.

### Claim 11

A lyophilized composition comprising nanoparticle complexes having an outer surface, wherein each of the nanoparticle complexes comprises:
albumin;
between about 100 to about 1000 bevacizumab antibodies, each having a hydrophobic Fc portion and a VEGF-binding portion, wherein the VEGF-binding portion is arranged on the outer surface of the complex; and
paclitaxel;
said nanoparticle complexes being lyophilized, and wherein upon reconstitution with an aqueous solution the VEGF-binding portions of said antibodies remain arranged on the outer surface of the complexes and remain capable of binding to VEGF in vivo and the Fc portions are associated with said albumin; and further wherein said complexes have an average size of from about 130 nm to about 800 nm; wherein the lyophilized composition does not contain a bulking agent.