Astra Ab

T Cell Sciences, Inc.

T Cell Diagnostics, Inc.

Phytoceutica, Inc.

Global Pharma, Ltd.

Patrick C Kung

Stephen H Ip

Charles William Rittershaus

Wei-Tao Tian

Mary Ellen Snider

Jone-Long Ko

Robert V Skibbens

Larry D Henry

Nancy L Wood

Michael C Brown

Savvas C Makrides

George Henry Parsons

Alfred E Fox

Nancy Jones

Ying Jie Chen

Linda A McKeen

Linda A MacKeen

Linda A Mackeen

Patricia S Meisner

The present invention relates to monoclonal antibodies which recognize defined regions of the T-cell receptor (TCR). In a specific embodiment, the invention provides monoclonal antibodies which are reactive with a constant region of the alpha chain of the TCR. In particular embodiments, the invention relates to two monoclonal antibodies, termed &agr;F1 and &agr;F2, which react with two different epitopes on the framework region of the &agr; monomer of the TCR molecule. In another specific embodiment, the invention is directed to monoclonal antibodies reactive with a variable region of the beta chain of the TCR. In particular, the invention provides two monoclonal antibodies, termed W112 and 2D1, which react with &bgr; chain variable regions V&bgr;5.3 and V&bgr;8.1, respectively. In another specific embodiment, the invention is directed to monoclonal antibodies reactive with a variable region of the delta chain of the TCR. In particular, the invention provides monoclonal antibody &dgr;TCS1, isotype IgG2a. The monoclonal antibodies of the invention have value in diagnosis and therapy and are useful tools for study of the immune system.

Monoclonal antibodies reactive with defined regions of the T cell antigen receptor

Icariin-containing preparations obtained from the aerial parts of a plant of the genus Epimedium, comprising about 15% to about 95% icariin by weight and about 5% to about 80% non-icariin flavones by weight. Also disclosed are methods of obtaining such preparations from an Epimedium plant.

Icariin preparations

The present invention relates to monoclonal antibodies which recognize defined regions of the T-cell receptor (TCR). In a specific embodiment, the invention provides monoclonal antibodies which are reactive with a constant region of the alpha chain of the TCR. In particular embodiments, the invention relates to two monoclonal antibodies, termed .alpha.F1 and .alpha.F2, which react with two different epitopes on the framework region of the .alpha. monomer of the TCR molecule. In another specific embodiment, the invention is directed to monoclonal antibodies reactive with a variable region of the beta chain of the TCR. In particular, the invention provides two monoclonal antibodies, termed W112 and 2D1, which react with .beta. chain variable regions V.beta.5.3 and V.beta.8.1, respectively. In another specific embodiment, the invention is directed to monoclonal antibodies reactive with a variable region of the delta chain of the TCR. In particular, the invention provides monoclonal antibody .delta.TCS1, isotype IgG2a. The monoclonal antibodies of the invention have value in diagnosis and therapy and are useful tools for study of the immune system.

Monoclonal antibodies reactive with defined regions of the T cell

The invention is directed to monoclonal antibodies reactive with a member of the V.beta.3 family variable region of the beta chain of the TCR. More particularly, the invention provides for detection of the V.beta.3.1 subfamily. In a specific embodiment the invention provides for detection of V.beta.3.1, without cross-reacting with other V.beta.3 family variable regions. In a specific embodiment, the monoclonal antibodies of the invention do not react with V.beta.3.2. In particular, the invention provides monoclonal antibodies, termed 5E4 and 8F10, which react with the variable region of a member of the V.beta.3 family. In various embodiments of the invention, these antibodies, or fragments or derivatives thereof, can be used to bind with a member of the V.beta.3 family TCR variable region amino acid sequences, either as part of an intact TCR or peptide, or T cell-surface molecule, or a fragment thereof. The monoclonal antibodies are useful for diagnosis and therapy of autoimmune disease, in particular rheumatoid arthritis.

Monoclonal antibodies reactive with an epitope of a V.beta.3.1 variable

The present invention relates to novel pharmaceutical compositions of isoflavanoid derivatives useful for the treatment of male pattern baldness and alopecia areata, and their use in promoting the conversion of gray hair to the original pigment in hair follicles. Also described herein are methods for the synthesis of isoflavanoid derivatives.

Methods for the treatment of baldness and gray hair using isoflavonoid

The present invention relates to the production of full length T cell antigen receptor V region proteins. The invention provides for methods of expressing the proteins as well as expression vectors for enhanced production of V region proteins. The invention further provides for the V.beta.5.3 region protein. The proteins of the invention have uses in the diagnosis and therapy of immune disorders.

T cell antigen receptor V region proteins and methods of preparation

Cell-free or released T cell antigen receptors, immunoassays which allow the detection of the released T cell antigen receptor in cell culture supernatants, cell lysates, and biological fluids, as well as diagnostic and therapeutic compositions and methods for monitoring and treating certain diseases or disorders which elicit or involve a T cell response are described. The released T cell antigen receptors described herein differ from the cell membrane bound antigen receptors and appear to exist in a variety of forms, some of which may be complexed with other T cell determinants such as the T3 antigen. Despite the size heterogeneity of the released T cell antigen receptors or receptor/complexes, these may be reliably identified using anti-receptor antibodies, including, but not limited to, anti-major framework, anti-minor frarmework and anti-clonotypic antibodies which define particular epitopes of the released T cell receptor or receptor/complex. The immunoassays described herein may be used to test for the presence of the released receptor or receptor/complex in biological samples and may be used to diagnose or monitor patients with disorders or diseases that elicit or involve T cell response who exhibit elevated serum level of the receptor or receptor/complex. In addition, the cell free T cell antigen receptors themselves may be used diagnostically and/or therapeutically for diseases or conditions that are not easily addressed using immunoglobulins.

Cell free T cell antigen receptor beta chain and its clinical utilities

The present invention is directed to the measurement of soluble leukocyte surface markers, soluble T cell growth factor receptors, soluble complement receptors, soluble T cell differentiation antigens, or related soluble molecules or fragments thereof, and the use of such measurements in the diagnosis and therapy of diseases and disorders. The invention is also directed to the measurement of soluble CD35 (sCD35) or fragments thereof, and the use of such measurements in detecting disease or disorders. A polyclonal sandwich assay is provided for the detection and/or measurement of soluble CD35. The invention further relates to the measurement of total leukocyte markers or fragments thereof, and the use of such measurements in the detection and diagnosis of diseases or disorders. The term 'total' leukocyte marker used herein refers to the total amount of a leukocyte marker in a sample, including that present in membrane and intracellular compartments and extracellular soluble compartments. Measurements of a total leukocyte marker can be used to determine the approximate amount in a body fluid sample of leukocytes positive for the leukocyte marker. In a further embodiment, the invention relates to the measurement of both the amount of total leukocyte marker and the amount of the soluble form of the leukocyte marker and a comparison of the measured levels.

Therapeutic and diagnostic methods using leukocyte surface antigens

The present invention is directed to the measurement of soluble T cell growth factor receptors, soluble T cell differentiation antigens, or related soluble molecules or fragments thereof, and the use of such measurements in the diagnosis, staging, and therapy of diseases and disorders. Specific embodiments involve the diagnosis and monitoring of therapy using absolute values of such soluble molecules. Further embodiments involve detecting a change in the levels of such soluble molecules, in the diagnosis and therapy of diseases and disorders. In specific embodiments, measurements of interleukin-2 receptor levels can be made to detect lung cancer, or to stage squamous cell lung carcinoma. In other embodiments, detection of increases in both soluble IL2R and creatinine in the body fluid of a transplant patient can be used to differentially diagnose renal allograft rejection from infection. The invention is also directed to methods for measurement of soluble CD4 antigens, which measurements can be used, in a specific embodiment, to diagnose a state of immune activation, to diagnose rheumatoid arthritis, to monitor therapeutic efficacy (e.g. of AIDS treatments), or to stage adult T cell leukemia in a patient. In another aspect, the invention relates to the detection, staging, and monitoring of therapy of diseases and disorders by measuring a plurality of soluble T cell markers.

Therapeutic and diagnostic methods using soluble T cell surface molecules

Monoclonal antibodies reactive with defined regions of the T-cell

The present invention is directed to the measurement of soluble T cell growth factor receptors, soluble T cell differentiation antigens, or related soluble molecules or fragments thereof, and the use of such measurements in the diagnosis and therapy of diseases and disorders. The measurement of such molecules can be valuable in monitoring the effect of a therapeutic treatment on a subject, detecting and/or staging a disease in a subject, and in differential diagnosis of a physiological condition in a subject. These measurements can also aid in predicting therapeutic outcome and in evaluating and monitoring the immune status of patients. In specific embodiments, measurements of serum or plasma interleukin-2 receptor levels can be made, to detect or stage leukemia or lymphoma. In other embodiments, IL2R levels, or CD8 levels, can be used to differentially diagnose renal allograft rejection, as distinguished from Cyclosporin A nephrotoxicity. In another embodiment, CD8 levels can be measured to differentially diagnose rheumatoid arthritis, as distinct from other joint diseases. In particular embodiments, measurements of the soluble T cell surface molecules can be accomplished by sandwich enzyme immunuoassays.

Methods are provided for detecting and determining the amount in a sample of an antigenic determinant from an antigen receptor derived and released from a T cell or NK cell. Methods are also provided for detecting and determining the amount in a sample of an antigenic determinant from a complex of at least a portion of an antigen receptor derived from and released from a T cell or NK cell and a protein complex. These methods form the bases for methods of diagnosing and monitoring in a subject a disease characterized by the presence or an amount different from a normal subject of one of these antigenic determinants in a body fluid. A soluble antigen receptor or complex thereof derived from a T cell or a NK cell but free of such T cell or NK cell is also provided.

Growing community of inventors

Lexington, MA, United States of America

Patrick C Kung