# US 7,408,039 B2 · Kits for treatment of hematologic disorders

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- Number: US 7,408,039 B2
- Document ID: US7408039B2
- Status: Granted
- Kind: B2
- Application number: 10/374,302
- Filed: 2003-02-25
- Published: 2003-08-21
- Granted: 2008-08-05
- Earliest claimed: 1997-11-14
- Assignees: The General Hospital Corporation
- Inventors: Megan Sykes; Thomas R. Spitzer
- Web page: https://patentgrep.com/patent/US7408039B2

## CPC

- A61K 39/39541: {against normal tissues, cells}
- A61K 31/675: having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
- A61K 35/28: Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
- A61K 40/10: characterised by the cell type used
- A61K 40/11: T-cells, e.g. tumour infiltrating lymphocytes [TIL] or regulatory T [Treg] cells; Lymphokine-activated killer [LAK] cells
- A61K 40/22: Immunosuppressive or immunotolerising
- A61K 40/32: T-cell receptors [TCR]
- A61K 40/418: {Antigens related to induction of tolerance to non-self}
- A61K 40/42: Cancer antigens
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 7/00: Drugs for disorders of the blood or the extracellular fluid
- A61P 7/02: Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
- A61P 35/00: Antineoplastic agents
- A61P 35/02: specific for leukemia
- A61K 2239/38: characterised by the dose, timing or administration schedule
- A61K 2239/48: Blood cells, e.g. leukemia or lymphoma
- Y10S 424/809: involving immunoglobulin or antibody fragment, e.g. fab', fv, fc, heavy chain or light chain
- Y10S 435/81: Packaged device or kit
- 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
- Y10S: TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS

## Abstract

The inventors have discovered that hematologic disorders, e.g., both neoplastic (hematologic cancers) and non-neoplastic conditions, can be treated by the induction of mixed chimerism using myeloreductive, but not myeloablative, conditioning. Methods of the invention reduce GVHD, especially GVHD associated with mismatched allogeneic or xenogeneic donor tissue, yet provide, for example, significant graft-versus-leukemia (GVL) effect and the like.

## Claims

### Claim 1

A kit for reducing graft versus host disease (GVHD) in a transplant recipient having a neoplastic hematological disorder comprising at least one cytoreductive agent; an anti-CD2 antibody, or antigen-binding fragment thereof, wherein the anti-CD2 antibody is BTI-322 produced by the hybridoma deposited under ATCC number HB-11423; and an agent which blocks a CD28-B7 costimulatory pathway of T cell activation or a CD40-gp39 costimulatory pathway of T cell activation.

### Claim 2 (depends on 1)

The kit of claim 1, wherein the cytoreductive agent is selected from the group consisting of alkylating agents, alkyl sulphonates, nitrosoureas, triazenes, antimetabolites, pyrimidine analogs, purine analogs, vinca alkaloids, epipodophyllotoxins, antibiotics, dibromomannitol, deoxysperguialine, dimethyl myleran and thiotepa.

### Claim 3 (depends on 2)

The kit of claim 2 wherein the alkylating agent is cyclophosphamide.

### Claim 4 (depends on 2)

The kit of claim 2 wherein the alkylating agent is melphalan.

### Claim 5 (depends on 2)

The kit of claim 2 wherein the alkyl sulphonates is busulphan.

### Claim 6 (depends on 2)

The kit of claim 2 wherein the purine analog is selected from the group consisting of fludarabine, idarubicin, cytosine arabinoside, mercaptopurine, and thioguanine.

### Claim 7 (depends on 2)

The kit of claim 2 wherein the antibiotic is selected from the group consisting of dactinomycin, daunorubicin, doxorubicin, bleomycin, plicamycin and mitomycin.

### Claim 8 (depends on 1)

The kit of claim 1, further comprising a pharmaceutically acceptable carrier.

### Claim 9 (depends on 1)

The kit of claim 1, wherein the agent which blocks a costimulatory pathway of T cell activation is a CTLA4-IgG fusion protein.

### Claim 10 (depends on 1)

The kit of claim 1, wherein the agent which blocks a costimulatory pathway of T cell activation is an agent which blocks the CD28-B7 pathway.

### Claim 11 (depends on 1)

The kit of claim 1, wherein the agent which blocks a costimulatory pathway of T cell activation is an agent which blocks the CD40-gp39 pathway.

### Claim 12 (depends on 1)

The kit of claim 1, wherein the agent which blocks a costimulatory pathway of T cell activation is an antibody.

### Claim 13

A kit for reducing graft versus host disease (GVHD) in a transplant recipient having a hematological disorder comprising cyclophosphamide and an anti-CD2 antibody, or antigen-binding fragment thereof, wherein the antibody is BTI-322 produced by the hybridoma deposited under ATCC number HB-11423.