# US 11,028,176 B2 · Anti-peripheral lymph node addressin antibodies and uses thereof

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- Number: US 11,028,176 B2
- Document ID: US11028176B2
- Status: Granted
- Kind: B2
- Application number: 16/788,773
- Filed: 2020-02-12
- Published: 2020-08-13
- Granted: 2021-06-08
- Earliest claimed: 2019-02-13
- Assignees: The Brigham and Women's Hospital, Inc.
- Applicants: The Brigham and Women's Hospital, Inc.
- Inventors: Reza Abdi
- Web page: https://patentgrep.com/patent/US11028176B2

## CPC

- C07K 16/2854: {against selectins, e.g. CD62}
- A61K 47/65: Peptidic linkers, binders or spacers, e.g. peptidic enzyme-labile linkers
- A61K 47/6849: {the antibody targeting a receptor, a cell surface antigen or a cell surface determinant}
- A61K 47/6929: {the form being a nanoparticle, e.g. an immuno-nanoparticle}
- A61P 35/00: Antineoplastic agents
- C07K 16/30: from tumour cells
- A61K 2039/505: {comprising antibodies}
- 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

## Abstract

The present disclosure provides, inter alia, anti-peripheral lymph node addressin antibodies and antigen binding fragments thereof. The present disclosure also provides compositions comprising drug-containing polymeric particles that mimic lymphocyte migration in vivo and can specifically deliver immunosuppressive or immunoregulatory drugs to lymphoid tissues and sites of chronic inflammation where T-cell activation and T-cell mediated injury are occurring; such compositions comprise the antibodies or antigen-binding fragments thereof described in the disclosure. The present disclosure also comprises antibody-drug conjugates and compositions comprising the antibody-drug conjugates. Methods of preparing and using these antibodies, antigen-binding fragments thereof, and compositions thereof are also provided.

## Claims

### Claim 1

An anti-peripheral lymph node addressin (PNAd) antibody, or a PNAd-binding fragment thereof, comprising:
(a) a heavy chain variable region (VH), wherein the VH comprises a VH complementarity determining region 1 (CDR1) comprising the amino acid sequence of SEQ ID NO:3, a VH CDR2 comprising the amino acid sequence of SEQ ID NO:4, and a VH CDR3 comprising the amino acid sequence of SEQ ID NO:5; and
(b) a light chain variable region (VL), wherein the VL comprises a VL CDR1 comprising the amino acid sequence of SEQ ID NO:8, a VL CDR2 comprising the amino acid sequence of SEQ ID NO:9, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO:10.

### Claim 2 (depends on 1)

The antibody, or PNAd-binding fragment thereof, of claim 1, wherein the VH comprises a VH framework region 1 (FR1) comprising the amino acid sequence set forth in SEQ ID NO:11, a VH FR2 comprising the amino acid sequence set forth in SEQ ID NO:12, a VH FR3 comprising the amino acid sequence set forth in SEQ ID NO:13, and a VH FR4 comprising the amino acid sequence set forth in SEQ ID NO:14.

### Claim 3 (depends on 1)

The antibody, or PNAd-binding fragment thereof, of claim 1, wherein the VL comprises a VL FR1 comprising the amino acid sequence set forth in SEQ ID NO:15, a VL FR2 comprising the amino acid sequence set forth in SEQ ID NO:16, a VL FR3 comprising the amino acid sequence set forth in SEQ ID NO:17, and a VL FR4 comprising the amino acid sequence set forth in SEQ ID NO:18.

### Claim 4 (depends on 1)

The antibody, or PNAd-binding fragment thereof, of claim 1, wherein the VH comprises the amino acid sequence set forth in SEQ ID NO:2.

### Claim 5 (depends on 1)

The antibody, or PNAd-binding fragment thereof of claim 1, wherein the VL comprises the amino acid sequence set forth in SEQ ID NO:7.

### Claim 6 (depends on 1)

The antibody, or PNAd-binding fragment thereof of claim 1, wherein the VH comprises the amino acid sequence set forth in SEQ ID NO:2 and the VL comprises the amino acid sequence set forth in SEQ ID NO:7.

### Claim 7 (depends on 1)

The antibody, or PNAd-binding fragment thereof, of claim 1, which is a monoclonal antibody.

### Claim 8 (depends on 1)

The antibody, or PNAd-binding fragment thereof, of claim 1, which is a murine antibody.

### Claim 9 (depends on 1)

The antibody, or PNAd-binding fragment thereof, of claim 1, which is a chimeric antibody.

### Claim 10 (depends on 1)

The antibody, or PNAd-binding fragment thereof, of claim 1, which is a humanized antibody.

### Claim 11 (depends on 1)

The antibody, or PNAd-binding fragment thereof, of claim 1, which is an antibody.

### Claim 12 (depends on 11)

The antibody, or PNAd-binding fragment thereof, of claim 11, which comprises human-derived heavy chain and light chain constant regions.

### Claim 13 (depends on 11)

The antibody, or PNAd-binding fragment thereof, of claim 11, which comprises a heavy chain constant region of isotype immunoglobulin mu (IgM).

### Claim 14 (depends on 1)

The antibody, or PNAd-binding fragment thereof, of claim 1, which is a PNAd-binding fragment of the antibody.

### Claim 15 (depends on 14)

The antibody, or PNAd-binding fragment thereof, of claim 14, wherein the PNAd binding fragment is selected from the group consisting of a single chain Fv fragment (scFv), an F(ab′) fragment, an F(ab) fragment, and an F(ab′)2 fragment.

### Claim 16 (depends on 1)

The antibody, or PNAd-binding fragment thereof, of claim 1, which is conjugated to an agent.

### Claim 17 (depends on 16)

The antibody, or PNAd-binding fragment thereof, of claim 16, wherein the agent is an imaging agent, a cytotoxic agent, or a drug.

### Claim 18 (depends on 16)

The antibody, or PNAd-binding fragment thereof, of claim 16, wherein the agent is a drug-containing polymeric particle.

### Claim 19 (depends on 18)

The antibody, or PNAd-binding fragment thereof, of claim 18, wherein the drug containing polymeric particle comprises an immunosuppressive or immunoregulatory drug.

### Claim 20 (depends on 16)

The antibody, or PNAd-binding fragment thereof, of claim 16, wherein the conjugation is covalent conjugation.

### Claim 21 (depends on 16)

The antibody, or PNAd-binding fragment thereof, of claim 16, wherein the conjugation is via a linker.

### Claim 22 (depends on 21)

The antibody, or PNAd-binding fragment thereof, of claim 21, wherein the linker is polyethylene glycol.

### Claim 23 (depends on 1)

A pharmaceutical composition comprising a therapeutically effective amount of the antibody or PNAd-binding fragment thereof of claim 1 and a pharmaceutically acceptable carrier.

### Claim 24 (depends on 18)

A pharmaceutical composition comprising a therapeutically effective amount of the antibody or PNAd-binding fragment thereof of claim 18 and a pharmaceutically acceptable carrier.

### Claim 25 (depends on 1)

The antibody, or PNAd-binding fragment thereof, of claim 1, which is a diabody.
