# US 5,705,158 A · Treatment of infectious and inflammatory lesions

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- Number: US 5,705,158 A
- Document ID: US5705158A
- Status: Granted
- Kind: A
- Application number: 08/469,992
- Filed: 1995-06-06
- Granted: 1998-01-06
- Earliest claimed: 1988-07-29
- Assignees: Immunomedics, Inc.
- Inventors: Hans John Hansen; Milton David Goldenberg
- Web page: https://patentgrep.com/patent/US5705158A

## CPC

- A61K 51/1018: {against material from animals or humans}
- A61K 47/6845: {the antibody targeting a cytokine, e.g. growth factors, VEGF, TNF, a lymphokine or an interferon}
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 31/00: Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P 31/04: Antibacterial agents
- A61P 31/10: Antimycotics
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A61K 2123/00: Preparations for testing in vivo
- Y10S 530/866: involving immunoglobulin or antibody fragment, e.g. fab', fab, fv, fc, heavy chain or light chain
- 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

A polyspecific anti-leukocyte antibody conjugate for targeting foci of leukocyte accretion comprises an immunoreactive polyspecific composite of at least two different substantially monospecific antibodies or antibody fragments, conjugated to at least one imaging agent, wherein at least two of said antibodies or antibody fragments specifically bind to different leukocyte cell types. A method for targeting an imaging agent to an inflammatory or infectious lesion comprises injecting a mammal parenterally with an effective amount for targeting of the above anti-leukocyte imaging conjugate. A therapeutic anti-leukocyte antibody-agent conjugate for targeting foci of leukocyte accretion comprises at least one immunoreactive substantially monospecific antibody or antibody fragment which specifically binds to at least one leukocyte cell type, conjugated to at least one therapeutic antimicrobial agent. A method of treatment of an infectious lesion comprises injecting a mammal parenterally with an effective amount for therapy of the above anti-leukocyte therapeutic conjugate.

## Claims

### Claim 1

A polyspecific anti-leukocyte antibody conjugate for enhanced targeting to leukocyte accretion, comprising at least one antimicrobial therapeutic agent conjugated to an immunoreactive polyspecific composite which specifically binds to at least two types of leukocytes, wherein said composite comprises at least two different substantially monospecific antibodies or antibody fragments which are chemically bound to one another either directly or through one or more linkers.

### Claim 2 (depends on 1)

A polyspecific anti-leukocyte antibody conjugate according to claim 1, wherein said at least two types of leukocytes are selected from the group consisting of granulocytes, monocytes, B-lymphocytes and T-lymphocytes.

### Claim 3 (depends on 1)

A polyspecific anti-leukocyte antibody conjugate according to claim 1, wherein each said antibody or antibody fragment is monoclonal.

### Claim 4 (depends on 1)

A polyspecific anti-leukocyte antibody conjugate according to claim 1, wherein said substantially monospecific antibody fragments are selected from the group consisting of F(ab').sub.2, Fab' and Fab.

### Claim 5 (depends on 1)

A polyspecific anti-leukocyte antibody conjugate according to claim 1, wherein least at one of said antibodies or antibody fragments specifically binds to the Ia(DR) antigen.

### Claim 6 (depends on 1)

A polyspecific anti-leukocyte antibody conjugate according to claim 1, wherein said therapeutic agent is an antibacterial agent.

### Claim 7 (depends on 1)

A polyspecific anti-leukocyte antibody conjugate according to claim 1, wherein said therapeutic agent is an antiviral agent.

### Claim 8 (depends on 1)

A polyspecific anti-leukocyte antibody conjugate according to claim 1, wherein said therapeutic agent is an antifungal agent.

### Claim 9 (depends on 1)

A polyspecific anti-leukocyte antibody conjugate according to claim 1, wherein said therapeutic agent is an antiparasitic agent.

### Claim 10 (depends on 1)

A polyspecific anti-leukocyte antibody conjugate according to claim 1, wherein said different substantially monospecific antibodies or antibody fragments are bound directly to one another.

### Claim 11 (depends on 8)

A polyspecific anti-leukocyte antibody conjugate according to claim 8, wherein said different substantially monospecific antibodies or antibody fragments are covalently bound to one another through a linker.

### Claim 12 (depends on 1)

A method of treatment of an infectious lesion by enhanced targeting to leukocyte accretion, which comprises injecting a mammal parenterally with an effective amount for therapy of the polyspecific anti-leukocyte antibody conjugate of claim 1.

### Claim 13 (depends on 12)

The method of claim 12, further comprising the step of parenterally administering to the subject, at a time after administration of said polyspecific anti-leukocyte antibody conjugate sufficient to permit maximum selective uptake thereof by leukocytes at the site of said lesion, a second, unlabeled antibody or antibody fragment which specifically binds to said polyspecific anti-leukocyte antibody conjugate, in an amount sufficient to increase the therapeutic index of said therapy agent by at least about 10 percent.

### Claim 14 (depends on 1)

A sterile injectable preparation for enhanced targeting of an antimicrobial therapeutic agent to an infectious lesion, comprising an effective amount for therapy of the polyspecific anti-leukocyte antibody conjugate of claim 1, in a pharmaceutically acceptable sterile injection vehicle.

### Claim 15 (depends on 1)

A kit for use in targeting an infectious lesion by enhanced targeting to leukocyte accretion comprising the polyspecific anti-leukocyte antibody conjugate of claim 1 in a sterile container.

### Claim 16 (depends on 15)

The kit of claim 15, further comprising a second, unlabeled antibody or antibody fragment which specifically binds to said polyspecific anti-leukocyte antibody conjugate, said second, unlabeled antibody or antibody fragment being provided in a separate sterile container from said polyspecific anti-leukocyte antibody conjugate.
