Drug compositions and their use in treating human or other mammalian patients

• US 4,764,359 A
• Filed: 12/16/1985
• Issued: 08/16/1988
• Est. Priority Date: 05/25/1984
• Status: Expired due to Term

• Current Assignee: Jerome H. Lemelson
• Original Assignee: Jerome H. Lemelson
• Inventors: Lemelson, Jerome H.
• Primary Examiner(s): Nucker, Christine M.
• Application Number:
  US06/809,207
• Time in Patent Office: 974 Days
• Field of Search: 424/1.1, 424/9, 424/19, 424/85, 424/450, 424/457
• US Class Current: 424/450
• CPC Class Codes: A61K 2121/00 Preparations for use in therapy
• CPC Class Codes: A61K 41/0095 Boron neutron capture therapy, i.e. BNCT, e.g. using boronated porphyrins
• CPC Class Codes: A61K 47/6957 the form being a device or a kit, e.g. stents or microdevices
• CPC Class Codes: A61K 49/0004 Screening or testing of compounds for diagnosis of disorders, assessment of conditions, e.g. renal clearance, gastric emptying, testing for diabetes, allergy, rheuma, pancreas functions
• CPC Class Codes: A61K 51/04 Organic compounds
• CPC Class Codes: Y10S 424/812 Liposome comprising an antibody, antibody fragment, antigen, or other specific or nonspecific immunoeffector

Abstract

Drug compositions formed as individual units, a multitude of which are employed as one or more doses, to reduce or aleviate cancer in a living being by targeting to and destroying cancer cells. In a preferred form, each drug unit is formed of an antibody, such as a monoclonal antibody targeted to a specific type of antigen, such as defined by a specific form of cancer, which antibody is united with or bonded to a white blood cell such as a macrophage or lymphocyte, preferably one which has been treated or activated with an immune system activator of a class referred to as lymphokines. One of such activators which may be so employed, is interleukin-2, which, in one embodiment, forms part of the drug unit. The drug unit may also include a microcapsule containing one or more of such lymphokine activated killer cells encapsulated therein and releasable therefrom, preferably after the drug unit has been targeted to a cancer cell or tumor by the antibody attached thereto. In a particular form, both the antibody and one or more of the white blood cells, lymphocytes or macrophages, cooperate in attacking the cancer cell or cells at the targeted site and the procedure progresses as cancer cells are destroyed exposing other cancer cells to additional drug units which feed to the cancer site in blood flow, in a manner to totally destroy the tumor or put into regression.

Claims

1. drug composition for use in the treatment of a disease, such as cancer, defined by a multitude of drug units composed of:

(a) a first drug unit component which is targeted to a specific antigen of a disease existing within a living being,

(b) a second drug unit component containing at least one cell destroying killer cell,

(c) said first drug unit component and said second drug unit component defining a unitary assembly wherein a portion of the surface of said first component extends outwardly from said assembly and is free to engage and become attached to antigens existing within a living being to which said drug unit is administered.

2. A drug composition in accordance with claim 1 wherein said first drug unit component comprises an antibody such as a monoclonal antibody targeted to a specific type of cancer cell.

3. A drug composition in accordance with claim 1 wherein sid first drug unit component comprises an antibody fragment targeted to carcinoembronic antigen (CEA) and the drug composition formed of a multitude of such units is in a fluid injectable form.

4. A drug composition in accordance with claim 1 provided in an injectable fluid form and further including a multitude of cell destroying killer cells mixed with said multitude of drug units in said fluid.

5. A drug composition in accordance with claim 1 wherein said second drug unit component is a lymphocyte which has been incubated with interlukin-2 and defines a lymphokineactivated killer cell deadly to a specific cancer, said lymphocyte being derived from the blood of a person to whom such drug composition is administered.

6. A drug composition in accordance with claim 1 including a material interposed between and bonded to said first and said second drug unit components preventing interaction between the two components.

7. A drug composition in accordance with claim 6 wherein said material which is interposed between said first and second drug unit components comprises a coating completely surrounding said second drug unit component, the material comprising said coating being degradeable to expose said second drug unit component within the body of a living being receiving said drug composition at a rate such that exposure of said second drug unit component occurs after targeting of the drug unit to a specific type of antigen within the body occurs.

8. A drug composition in accordance with claim 1 including a microcapsule surrounding and encapsulating said second drug unit component and means for releasing said second drug component from said microcapsule after the drug unit has become targeted to an antigen, such as defining a cancer cell existing in a living being to whom such drug composition has been administered.

9. A drug composition in accordance with claim 8 wherein said first drug unit component is composed of a pluralty of monoclonal antibodies or fragments of monoclonal antibodies targeted to at least two different types of antigens defining different types of cancer cells, and a plurality of said cell destroying killer cells contained within said microcapsule.

10. A drug composition in accordance with claim 6 wherein said material interposed between said drug unit components comprises a microcapsule, a plurality of said second drug unit components encapsulated within said microcapsule, said microcapsule being biodegradeable after said drug composition is administered to a living being in a manner to release the killer cells therefrom after said drug unit has been targeted to the antigen defined by said first drug unit component.

11. A drug composition in accordance with claim 1 including a plurality of said drug unit components and respective biodegradeable encapsulation means for respective of said second drug unit components, means for cuasing respective quantities of said respective encapsulation means to biodegrade at different times after a dose of said drug composition has been administered to the body of a patient being treated therewith and wherein at least certain of said drug unit components are so released after the drug unit becomes targeted to an antigen of a cancer cell existing within the body of said patient.

12. A drug composition in accordance with claim 1 including a lipid vesicule, surrounding and encapsulating said drug unit component, said first drug unit component being bound to the outside surface of said vesicule.

13. A drug composition in accordance with claim 1 including means for encapsulating said second drug unit component and means for releasing said cell destroying killer cell from such encapsulation, and a biodegradeable bioadhesive coating said encapsulation means for binding said drug unit to the surface of tissue in the vicinity of the antigen to which said first drug unit component targets to.

14. A drug composition for use in treating a tumor, such as a malignancy, formed of a multitude of drug units, which drug units comprise:

(a) a killer cell in the form of a lymphocyte rendered deadly to cells of a malignancy when in contact

(b) encapsulating means in the form of a wall of material surrounding said killer cell,

(c) an antibody having a surface portion configured to attach said antibody to a cell of said malignancy,

(d) said antibody being bound to the outside surface of said wall surrounding said killer cell wherein a sufficient portion of the surface of said antibody protrudes from said wall to permit said antibody to target and become attached to a cell of said tumor, and

(e) means for releasing said killer cell from encapsulation by said encapsulating means to permit it to attack a cell of a malignancy adjacent said drug unit after said antibody has become targeted to said malignancy.

15. A drug composition in accordance with claim 14 said wall of said material surrounding and encapsulating said killer cell normally separates said antibody from said killer cell and prevents said killer cell from attacking normal body cells while said drug unit is passing through the body to the site of a malignancy.

16. A drug composition in accordance with claim 14 including means for providing an opening in the wall of said encapsulating material after the drug unit targets to targets to an antigen within the body of a living being to which said drug composition has been administered.

17. A method of treating a tumor, such as malignancy, existing in a living being comprising:

(a) forming a drug composition of a multitude of drug units, which drug units are composed of a biological element targeted to an intracellular marker substance, produced by or associated with a tumor to be treated, and at least one killer cell, such as a phage contained by said drug unit and carried thereby,

(b) administering a dose of said drug composition to a living being having a tumor to which said antibody is targetable and permitting drug units of said dose to target to respective portions of said tumor by permitting the antibodies thereof to attach to respective cells of said tumor,

(c) after said drug units become targeted adjacent the tumor, releasing the killer cells thereof from the drug units and permitting said killer cells to attack respective cells of the tumor and to destroy the cells they attack,

(d) providing a sufficient number of said drug units administered to the body of said living being to effect the destruction of said tumor under the action of killer cells.

18. A method in accordance with claim 17 wherein step (c) is effected by encapsulating said killer cells in respective microcontainers and releasing said killer cells from said microcontainers adjacent said tumors.

19. A method in accordance with claim 18 wherein said killer cells are released from said microcontainers by destruction of the microcontainers at the sites of said tumor.

20. A method in accordance with claim 17 wherein said drug units are formed with a plurality of killer cells disposed in a microencapsulating means from which encapsulating means said plurality of killer cells are time control released in a manner to permit individual killer cells to attack different cells of said tumor.