# US 11,433,023 B2 · Albumin-PD-1 paclitaxel nanoparticle complex compositions and methods of making and using the same

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 11,433,023 B2
- Document ID: US11433023B2
- Status: Granted
- Kind: B2
- Application number: 15/456,377
- Filed: 2017-03-10
- Published: 2017-06-29
- Granted: 2022-09-06
- 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/US11433023B2

## 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 comprising
albumin;
antibodies, each having a programmed cell death protein 1 (PD-1)-binding portion;
and paclitaxel;
said nanoparticle complexes being lyophilized, and wherein upon reconstitution with an aqueous solution the nanoparticle complexes have binding specificity for PD-1 expressed by a cancer cell in vivo, wherein the antibodies are not pembrolizumab, wherein said complexes have an average size of less than 1 μm, and wherein the antibodies are associated with the albumin through non-covalent bonds.

### 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 1)

The lyophilized composition of claim 1, wherein less than 0.01% of nanoparticle complexes have a size greater than 800 nm.

### Claim 5 (depends on 1)

The lyophilized composition of claim 1, wherein said nanoparticle complexes have an average size of about 160 nm.

### Claim 6 (depends on 1)

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

### Claim 7 (depends on 1)

The lyophilized composition of claim 1, wherein the nanoparticle complexes have a dissociation constant between about 1×10−11 M and about 1×10−9 M.

### Claim 8 (depends on 1)

The lyophilized composition of claim 1 which does not contain a bulking agent.

### Claim 9 (depends on 1)

The lyophilized composition of claim 1, wherein said nanoparticle complexes have an average size between about 130 nm and about 800 nm.

### Claim 10 (depends on 1)

The lyophilized composition of claim 1, wherein the ratio of albumin-paclitaxel nanoparticle to antibodies is between 10:1 and 10:30.

### Claim 11 (depends on 1)

The lyophilized composition of claim 1, wherein the ratio of albumin-paclitaxel nanoparticle to antibodies is between 10:2 and 10:6.

### Claim 12 (depends on 1)

The lyophilized composition of claim 1, wherein the antibodies are nivolumab.

### Claim 13 (depends on 12)

The lyophilized composition of claim 12, wherein less than 0.01% of nanoparticle complexes have a size greater than 800 nm.

### Claim 14 (depends on 12)

The lyophilized composition of claim 12, wherein said nanoparticle complexes have an average size between about 130 nm and about 800 nm.

### Claim 15 (depends on 12)

The lyophilized composition of claim 12, wherein the ratio of albumin-paclitaxel nanoparticle to antibodies is between 10:1 and 10:30.

### Claim 16 (depends on 12)

The lyophilized composition of claim 12, wherein the ratio of albumin-paclitaxel nanoparticle to antibodies is between 10:2 and 10:6.

### Claim 17 (depends on 1)

The lyophilized composition of claim 1, wherein each of the nanoparticle complexes comprises between about 100 and about 1000 antibodies.

### Claim 18 (depends on 1)

The lyophilized composition of claim 1, further comprising at least one additional cancer therapeutic agent.

### Claim 19 (depends on 1)

The lyophilized composition of claim 1, wherein the paclitaxel is associated with the albumin through non-covalent bonds.

### Claim 20 (depends on 12)

The lyophilized composition of claim 12, wherein the paclitaxel is associated with the albumin through non-covalent bonds.