Geneva, Switzerland
Geneva, Switzerland
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This invention relates generally to methods and compositions for identifying patient populations for diagnosis and treatment of Toll-like Receptor 4 (TLR4)-dependent disorders. In particular, the invention relates to detecting levels of anti-citrullinated protein antibodies (ACPA) and citrullinated peptides to identify patients having a TLR4-dependent disease and to identify patients who are likely to respond to anti-TLR4 therapy. The invention also relates to methods of treating, delaying the progression of, or otherwise ameliorating a symptom of a disorder in patients with elevated levels of ACPA and citrullinated peptides using agents that interfere with or otherwise antagonize TLR-4 signaling, including neutralizing anti-TLR4 antibodies.


Patent
NovImmune | Date: 2017-01-03

This invention provides monoclonal antibodies that recognize the Toll-like Receptor 4/MD-2 receptor complex, and monoclonal antibodies that recognize the TLR4/MD2 complex as well as TLR4 when not complexed with MD-2. The invention further provides methods of using the humanized monoclonal antibodies as therapeutics. This invention also provides soluble chimeric proteins, methods of expressing and purifying soluble chimeric proteins, and methods of using soluble chimeric proteins as therapeutics, in screening assays and in the production of antibodies.


Patent
NovImmune | Date: 2017-01-05

This invention provides monoclonal antibodies that recognize the Toll-like Receptor 4/MD-2 receptor complex, and monoclonal antibodies that recognize the TLR4/MD2 complex as well as TLR4 when not complexed with MD-2. The invention further provides methods of using the monoclonal antibodies as therapeutics. This invention also provides soluble chimeric proteins, methods of expressing and purifying soluble chimeric proteins, and methods of using soluble chimeric proteins as therapeutics, in screening assays and in the production of antibodies.


Grant
Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2012.2.4.4-1 | Award Amount: 11.24M | Year: 2012

Hemophagocytic lymphohistiocytosis (HLH) is a rare, devastating disease characterized by uncontrolled immune response that primarily affects young infants and children. HLH is usually fatal if untreated. Even when treated, the overall survival rate is still as low as 60-70%. No drug has been formally developed for the treatment of this disease and current treatment methods require the use of drugs which have not formally been developed for this indication which have an unfavourable safety profile. The cytokine interferon-gamma (IFN) was shown to play a key pathological role in the disease. It has been demonstrated that neutralization of IFN with a monoclonal antibody (mAb) reverts the disease and rescues animals from death in murine models of primary HLH. In patients, evidence points towards a correlation between levels of IFN and disease activity. In order to target IFN in patients with HLH, NovImmune generated and characterized a fully human mAb, NI-0501, that neutralizes the biological activity of human IFN. This consortium proposes an adaptive clinical trial with a pilot and a pivotal phase to provide the necessary data for Market Access Authorization for NI-0501 in HLH. The pilot phase will enroll only patients well-known to have a primary form of HLH and who relapsed after having responded to an initial treatment while the pivotal phase will open the recruitment to newly diagnosed HLH patients. The transition between the pilot and the pivotal phase will be governed by strict pre-defined transition rules and will only occur if a favorable benefit-risk profile has been demonstrated. During the course of the pilot phase the consortium will attempt to generate the necessary information to justify the inclusion in the pivotal phase of a broad range of HLH patient (secondary forms of the disease), for which the pivotal role of IFN will have been demonstrated thanks to the research activities of members of the consortium.


Patent
NovImmune | Date: 2016-09-26

Disclosed are antibodies that specifically bind Toll-like Receptor 4 (TLR-4), and to methods of using the anti-TLR4 antibodies as therapeutics and diagnostic agents.


The invention provides compositions and methods for generating libraries of DNA sequences encoding homologous polypeptides, and uses of the libraries to identify naturally diversified polypeptide variants. The invention also provides compositions and methods for generating collections of synthetic antibody fragments in which one or several complementary determining regions (CDR) are replaced by a collection of the corresponding CDR captured from a natural source. The invention further provides compositions and methods for diversifying a portion of a polypeptide by inserting a diversified sequence of synthetic or natural origin without the need for modification of the original polypeptide coding sequence.


Patent
NovImmune | Date: 2016-01-12

This invention provides fully human monoclonal antibodies that recognize the IL-6/IL-6R complex. The invention further provides methods of using such monoclonal antibodies as a therapeutic, diagnostic, and prophylactic.


Methods are provided to improve the expression of protein complexes by tuning the expression levels of each component required for the assembly of the complex. These methods are effective in limiting the expression of the dominant chain and, thus, equilibrating their relative abundance. The methods provided herein lead to a significant increase in productivity and final bispecific yields both in transient expression systems as well as in stably transfected mammalian cells.


Methods and compositions for treating hemophagocytic lymphohistiocytosis (HLH) are provided. The disclosure also relates generally to methods and compositions for diagnosing and treating disorders associated with elevated levels of CXCL9, elevated levels of total IFN, and other biomarkers. The disclosure also relates to methods of treating, delaying the progression of, or otherwise ameliorating a symptom of a disorder in patients with elevated levels of CXCL9 elevated levels of total IFN, and other biomarkers using agents that interfere with or otherwise antagonize interferon gamma (IFN) signaling, including neutralizing anti-IFN antibodies.


Patent
NovImmune | Date: 2016-03-14

The invention relates to the purification of bispecific antibodies carrying a different specificity for each binding site of the immunoglobulin molecule from a mixture of monospecific antibodies. The bispecific antibodies are composed of a single heavy chain and two different light chains, one containing a Kappa constant domain and the other a Lambda constant domain. This invention in particular relates to the isolation of these bispecific antibodies from mixtures that contain monospecific antibodies having two Kappa light chains or portions thereof and monospecific antibodies having two Lambda light chains or portions thereof. The invention also provides the methods of efficiently purifying these bispecific antibodies.

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