Invented by Peter Andreas Nicolai Reumert Wagtmann, Ivan Svendsen, Rozana Sten, Lene Hjorth Alifrangis, Rune Viig Overgaard, Novo Nordisk AS
Anti-KIR formulations work by blocking the KIR receptors on NK cells, which allows them to better recognize and attack cancer cells. This approach has shown promising results in clinical trials for various types of cancer, including leukemia, lymphoma, and multiple myeloma.
The market for Anti-KIR formulations is expected to grow significantly in the coming years, driven by the increasing prevalence of cancer and the need for more effective treatments. According to a report by Grand View Research, the global cancer immunotherapy market is expected to reach $126.9 billion by 2026, with Anti-KIR formulations being one of the key drivers of growth.
Several pharmaceutical companies are currently developing Anti-KIR formulations, including Innate Pharma, Bristol Myers Squibb, and Novartis. In 2020, Innate Pharma announced positive results from a Phase 1 clinical trial of its Anti-KIR drug, IPH5201, in patients with advanced solid tumors. The company is now planning to initiate a Phase 2 trial in 2021.
In addition to cancer, Anti-KIR formulations are also being studied for their potential use in treating autoimmune diseases, such as rheumatoid arthritis and lupus. These conditions are characterized by an overactive immune system, and Anti-KIR formulations could help to regulate the immune response and reduce inflammation.
Overall, the market for Anti-KIR formulations and their uses is a rapidly growing field with significant potential for improving cancer treatment and other immune-related conditions. As more clinical trials are conducted and new drugs are developed, we can expect to see continued growth and innovation in this area.
The Novo Nordisk AS invention works as follows
An IgG4 isotype anti?KIR antibody has been developed. It also contains novel anti-KIR anti-KIR formulations. These formulations can be used in combination with other IgG4 anti?KIR antibodies. The compositions, dosages and administration methods for NK cells activation and therapeutic uses of anti-KIR antibody are also described.
Background for Anti-KIR formulations and their uses
KIRs are polymorphic type 1-trans-membrane molecules that can be found on certain subsets lymphocytes including NK and T cells. KIRs interact in the alpha 1 or 2 domains of MHC Class I molecules. Haplo-identical stem cells transplantation (SCT), in patients with AML can result in activation and expansion of KIR-HLA mismatched NK cell lines. This results in a lower rate of leukemia relapse, reduced graft-versus host disease and markedly higher survival rates (Ruggeri and al., Science 2002, 295:2029-3). Clinical efficacy of haploidentical SCT can be explained by the molecular mechanism that NK cells-mediated tumor killing is controlled by inhibitory KIR receptors. These NK cells receptors transmit negative signals that inhibit NK-cell-mediated tumor killing by binding to specific HLA-B and -C ligands. HLA-B & -C molecules are highly variable in the population. Different HLA allotypes can be recognized by KIR2DL1 and KIR2DL2/3. It is common to find donors and recipients whose KIR and HLA do not match, meaning that the KIR of the donor does not bind to an HLA ligand in their recipient. These situations are ideal for activating NK cells because there is no transmission via KIR of inhibitory signals that do not bind HLA ligands. This SCT protocol is not accessible to all patients.
A humanized or fully human antiKIR antibody capable of blocking inhibitory KIR signalling is possible to achieve similar NK-mediated antileukemia activity. The WO2006/003179, 2007/072626, 2005/003172, 2005/003172, 2005/003168 and 2005/003168 describe anti-KIR antibodies with beneficial pharmacological properties that are useful in the treatment of infectious diseases and cancer. For clinical use of these antibodies, however, it is important to have optimized formulations and efficient administration regimens.
The invention discussed herein concerns anti-KIR antibody formulations and administration protocols, which are suitable for their use in stimulating physiological effects useful for the treatment of cancer or other diseases.
The present invention provides anti-KIR antibody compositions that, when administered, can modulate NK cells activity in vivo. These compositions can be used in specific dosages to efficiently occupy KIR receptors on the NK cells. They are useful for treating cancer and other viral diseases.
Provides also include the S241P anti-KIR antibody 1–7F9 (described under WO2008/003,179), new pharmaceutical fomulations that are compatible with the variant and/or the 1-7F9, methods for producing the same, as well as methods of using these compositions to promote physiological effects such treatment of cancer and viral diseases.
DESCRIPTION DU DRAWINGS
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FIG. “FIG. Annotated with peak start (Retention?R?) is the euted material from protein A. Vol-14 mL and Peak end (R.Vol-12 mL) were stored in a loop before being injected at the desalting columns. After desalting, fractions of the mixture were taken and fractions Annotated A2 & A3 were gathered and merged for further analysis.
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FIG. 7 displays the mean predicted PK profiles compared with the observed values in B6 mice. The combined B6/KIR?tgII model for PK prediction is used.
FIG. 8 is the mean predicted PK profile compared with the observed values for KIRtgII mice. The combined B6/KIR?tgII PK model is used to predict the models.
FIG. 9 displays mean predicted PK profiles compared with mean observed values in KIRtgI mice.
FIG. 10 is a schematic representation for the two-compartment model of pharmacokinetics that can be used to predict PK in humans and estimate PK in cynomolgus monkeys.
FIG. “FIG.
FIG. 15 shows the levels of CD107a on NK- and T-cells in patient blood after administration of Anti-KIR(1-7F9), where CD107a levels were increased on NK-cells 24h post-administration.
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