Texas Heart Institute

7 Hills Pharma LLC

Texas Biotechnology Corporation

Texas Children's Hospital

7 Hills Pharma Inc. and Texas Heart Institute

7 Hills Interests LLC

Peter Vanderslice

Darren G Woodside

Upendra K Marathi

Timothy P Kogan

Ronald J Biediger

Robert V Market

Pamela J Beck

Kaijun Ren

Michael M Savage

William C Gundlach, Iv

Ananth V Annapragada

James T Willerson

Eric A Tanifum

Richard Dixon

Eric Tanifum

C William Gundlach

Iv C William Gundlach

Iv William C Gundlach

Pharmaceutical compositions including one or more integrin activating compounds capable of enhancing an anti-tumor activity of one or more therapeutic antibodies, one or more immune checkpoint inhibitors, or mixtures thereof.

Compositions including a therapeutic antibodies and/or a checkpoint inhibitor and an integrin activating compound

Vaccine compositions including one or more antigens and one or more integrin agonists or activating compounds present in an amount sufficient to increase an immune response of a patient to the one or more antigens.

Integrin activator vaccine compositions

Disclosed herein is a composition comprising a plurality of liposomes having an average diameter of less than 400 nanometers, wherein the plurality of liposomes comprise: a first lipid or phospholipid; a second lipid or phospholipid which is derivatized with a polymer; and a sterically bulky excipient capable of stabilizing the liposomes; a third lipid or phospholipid derivatized with a polymer terminated with an integrin targeting component; DSPE or a fourth lipid or phospholipid derivatized with a group binding a contrast enhancing agent wherein the plurality of liposomes optionally encapsulates a payload component consisting of one or more bioactive agents.

Targeting nanoparticles

Methods for priming of vaccines including administering to a patient a composition including one or more integrin activating compounds capable of adjuvanting an antigen and capable of adjuvanting one or more antigens contained in a vaccine preparation.

Methods of administering novel integrin activator vaccine compositions

Integrin activator checkpoint inhibitor compositions

Compositions including one or more antigens and one or more integrin activating compounds capable of adjuvanting the one or more antigens contained and increasing an immune response to the one or more antigen in a vaccine preparation.

Small molecule integrin ligand mimetics facilitate integrin-ligand interactions, which may be used to prepare vaccines, adoptive cell therapies, immunotherapies for cancer, and a variety of other conditions. As integrin mediated cell-cell interactions are critical to antigen presentation and effector cell killing, increasing the efficiency of integrin receptor-ligand interactions will stabilize the immune synapse and improve effector functions. Compositions and methods including the mimetics enhance: (1) the priming of vaccines (including, but not limited to, cancer vaccines); (2) cytolytic activity of adoptive cell therapies (including, but not limited to &#x3b3;&#x3b4;T-cells, CTLs, NK, iNKT); (3) immunotherapies (including, but not limited to, negative checkpoint blockage strategies such as anti-CTLA-4 and anti-PD-1); and (4) biologic therapies (including, but not limited, to trastuzumab and rituxamab), whereby the mechanism-of-action includes antibody dependent cellular cytotoxicity (ADCC).

Compositions and methods for immunotherapies comprising small molecule integrin receptor-ligand agonist adjuvants

A method of enhancing binding of cells to an integrin-binding ligand comprises treating integrin-expressing cells in vitro with an agonist of integrin, wherein the integrin is selected from the group consisting of &#x3b1;4&#x3b2;1, &#x3b1;5&#x3b2;1, &#x3b1;4&#x3b2;7, &#x3b1;v&#x3b2;3 and &#x3b1;L&#x3b2;2, and contacting the treated cells with an integrin-binding ligand; integrin agonist compounds having the general formula I; methods of treating integrin-expressing cells with such agonists to enhance binding; and therapeutic methods comprising administering agonist-treated cells or agonist compounds to a mammal.

Agonists that enhance binding of integrin-expressing cells to integrin receptors

The present invention is directed to an isolated and purified cyclic peptide of from 5 to about 13 residues modeled after a portion of the CS1 peptide. A peptide of this invention preferably has the amino acid residue sequence of SEQ ID NO:2-14 or 16-42. The present invention is further directed to a process of selectively inhibiting the binding of &agr; &bgr; integrin to a protein such as VCAM-1, fibronectin or invasin. In accordance with that process, a cell that expresses &agr; &bgr; integrin is exposed to that protein in the presence of an effective inhibiting amount of such a peptide. The present invention is still further directed to a pharmaceutical composition containing a physiologically acceptable carrier and a cyclic peptide of the invention.

Process to inhibit binding of the integrin &agr;4&bgr;1 , to VCAM-1 fibronectin and cyclic peptides thereof

The present invention is directed to an isolated and purified cyclic peptide of from 5 to about 13 residues modeled after a portion of the CS1 peptide. A peptide of this invention preferably has the amino acid residue sequence of SEQ ID NO:2-14 or 16-42. The present invention is further directed to a process of selectively inhibiting the binding of .alpha..sub.4 .beta..sub.1 integrin to a protein such as VCAM-1, fibronectin or invasin. In accordance with that process, a cell that expresses .alpha..sub.4 .beta..sub.1 integrin is exposed to that protein in the presence of an effective inhibiting amount of such a peptide. The present invention is still further directed to a pharmaceutical composition containing a physiologically acceptable carrier and a cyclic peptide of the invention.

Process to inhibit binding of the integrin .alpha..sub.4 .beta..sub.1 to

The present invention is directed to an isolated and purified peptide comprising the LDV domain of the CSI peptide sequence or single amino acid substitutent analog thereof. A preferred peptide has the amino acid residue sequences shown in SEQ ID NOs:8-14, 17-23, 25, 28, and 51. The present invention is further directed to a process of inhibiting the binding of .alpha..sub.4 .beta..sub.1 integrin to a protein such as VCAM-1 or fibronectin comprising exposing a cell that expresses .alpha..sub.4 .beta..sub.1 integrin to the protein in the presence of an effective inhibiting amount of such a peptide. The present invention is still further directed to a pharmaceutical composition comprising a peptide of SEQ ID NO:8-102.

Growing community of inventors

Houston, TX, United States of America

Peter Vanderslice