Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai
Reexamination Certificate
1998-11-25
2001-04-17
Chan, Christina Y. (Department: 1644)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Peptide containing doai
C514S475000
Reexamination Certificate
active
06218361
ABSTRACT:
BACKGROUND OF THE INVENTION
Acute and chronic allograft rejection are the most common causes of allograft failure. A further understanding and improved treatment of acute and chronic rejection are of critical importance and will optimize transplantation as a successful treatment modality in certain disease states such as kidney and heart failure. The development of chronic rejection is reported to be associated with acute rejection. Indeed, acute allograft rejection episodes are most predictive for the development of chronic rejection. Chronic allograft rejection is a complex multicellular process which generally occurs months to years after organ grafting and is characterized by pathological features such as graft arteriosclerosis. Therefore, additional methods of suppressing acute allograft rejection can also increase the longevity of individuals with organ transplants.
Thus, there is a continued need to develop new and improved methods of inhibiting allograft rejection to promote the quality of life of subjects, such as human transplant patients.
SUMMARY OF THE INVENTION
This invention is based upon the discovery that anti-angiogenic agents inhibit allograft rejection in a subject, such as a mammal. As described herein acute and chronic allograft rejection in subjects with organ transplants are inhibited with anti-angiogenic agents. Thus, the present invention relates to a method of inhibiting allograft rejection in a subject comprising administering an effective amount of one or more anti-angiogenic agents. When the method of the present invention is used to treat acute allograft rejection the anti-angiogenic agent is not thalidomide.
As described herein the anti-angiogenic agent is a substance, such as a polypeptide, peptidomimetic, small organic molecule, sugar or lipid, that interferes, either directly or indirectly, with the development of new blood vessels. These anti-angiogenic agents inhibit allograft rejection. Specifically encompassed by the present invention is a method of treating a subject such as a mammal, including humans, wherein the subject is being treated for chronic allograft rejection. In another aspect of the invention a subject is being treated for acute allograft rejection. In one embodiment the anti-angiogenic agent is angiostatin. In another embodiment the anti-angiogenic agent is endostatin. In preferred embodiments, the anti-angiogenic agent is O-chloroacetylcarbamoyl) fumagillol (referred to herein as AGM-1470), or an analogue of AGM-1470, such as TNP-470. Specifically encompassed by the present invention is a method of inhibiting allograft rejection wherein the subject is being treated for an organ transplant. In preferred embodiment the transplanted organ is a kidney(s) or a heart.
A further embodiment of the present invention is a method of inhibiting allograft rejection wherein the anti-angiogenic agent is co-administered with an effective amount of one or more immunosuppressive agents. Specifically encompassed is a method of treating a subject wherein the subject is being treated for acute allograft rejection by co-administering one or more anti-angiogenic agents and one or more immunosuppressive agents.
The inventions described herein provide alternative and improved methods for the successfully inhibiting, interrupting the development of, or treating established allograft rejection in a subject. The invention thereby offers new and effective methods which are extremely useful in clinical settings for treating mammals, such as humans, following the transplantation of organs such as the heart and kidney.
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Briscoe David M.
Moulton Karen
Sayegh Mohamed H.
Chan Christina Y.
Children's Medical Center Corporation
DiBrino Marianne
Nixon & Peabody LLP
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