Neoplàsies hematològiques: Leucèmies, Limfomes i Mielomes

ANTIGEN BINDING MOLECULES AND METHODS OF USE

Resumen de: WO2024186927A2

The present disclosure describes antigen binding molecules, including antibodies, that specifically bind to the anti-CD20 scFv-14 or Gibbon ape leukemia virus gp70 protein, as well as molecules comprising the described sequences and cells presenting such molecules. The antigen binding molecules may be used in research, diagnostic, clinical, and other applications.

DENOSUMAB FORMULATION

Resumen de: WO2024184280A1

An aqueous pharmaceutical formulation having improved stability includes denosumab and a poloxamer, and preferably a histidine buffer and/or sugar or sugar alcohol. The formulation is for use in treating or preventing osteoporosis, loss of bone mass, skeletal-related events associated with multiple myeloma, solid tumor bone metastases, giant cell tumors of the bone or hypercalcemia.

COMPOSITIONS AND METHODS FOR TREATMENT, DIAGNOSIS, AND PROGNOSIS OF LEUKEMIA BASED ON LEUKEMIA-SPECIFIC GENE FUSIONS, MUTATIONS, AND VARIANTS

Resumen de: WO2024186944A2

Methods, compositions, computational methodologies, and kits for cost-effective and improved detection and characterization of leukemia mutations for treatment of leukemia. Leukemias frequently present with recurrent gene fusions, which can be drivers of disease pathophysiology. The disclosed approaches do not utilize amplification of polynucleotides, lowering energy requirements and current financial and socioeconomic barriers limiting access to diagnostics and treatments. The disclosed approaches facilitate identification of leukemia genomic variants and help stratify diseases by risk, facilitating improved therapy choices, including for cost-sensitive communities with limited access to biomedical testing services.

METHOD FOR TREATING ACUTE MYELOID LEUKEMIA USING VENETOCLAX IN CONJUNCTION WITH LINTUZUMAB-AC225

Resumen de: US2024299600A1

Provided are methods for treating acute myeloid leukemia that include administering a regimen of venetoclax and lintuzumab-Ac225, in which (a) the regimen includes a plurality of cycles, each cycle lasting from 28 to 60 days, (b) the regimen includes (i) orally administering venetoclax on days 1 and 2 of the first cycle at a ramp-up dosage, and thereafter orally administering 400 mg of venetoclax daily on days 3-21 of the first cycle and days 1-21 of each subsequent cycle, and (ii) intravenously administering lintuzumab-Ac225 on day 4, 5, 6 or 7 of each cycle at a dose of from 0.1 μCi/kg to 2.0 μCi/kg, and (c) the subject has a peripheral blast burden at or below 1,000 blast cells/μl. Also provided are related methods in which the regimen includes intravenously administering lintuzumab-Ac225 twice during each cycle.

SUBSTITUTED BICYCLIC AND TETRACYCLIC QUINONES AND RELATED METHODS OF USE

Resumen de: EP4427812A2

This invention is in the field of medicinal chemistry. In particular, the invention relates to small molecule compounds having bicyclic and tetracyclic quinone scaffolds which have antiproliferative activities through, for example, induction of reactive oxygen species. The invention further processes for preparing, and methods for using these compounds to treat cancer (e.g., pancreatic cancer, leukemia, non-small cell lung cancer, colon cancer, CNS cancer, melanoma, ovarian cancer, breast cancer, renal cancer, and prostate cancer).

METHODS FOR TREATMENT USING ADOPTIVE CELL THERAPY

Resumen de: EP4427810A2

Provided are adoptive cell therapy involving the administration of doses of cells for treating subjects with disease and conditions such as certain B cell malignancies, and related methods, compositions, uses and articles of manufacture. The cells generally express recombinant receptors such as chimeric antigen receptors (CARs). In some embodiments, the disease or condition is a large B cell lymphoma, such as a diffuse large B-cell lymphoma (DLBCL). Also provided are methods of assessing the risk of developing a toxicity related to a cell therapy, and methods of identifying subjects and methods of treating subjects based on the assessment of risks.

PHARMACEUTICAL COMPOSITION COMPRISING PI3K AND DNA-PK DUAL INHIBITOR FOR PREVENTING OR TREATING PERIPHERAL T CELL LYMPHOMA

Resumen de: EP4427751A1

The present invention relates to a composition for preventing or treating peripheral T-cell lymphoma, including a compound represented by formula 1 or pharmaceutically acceptable salts thereof. Specifically, the present invention relates to a pharmaceutical composition capable of effectively ameliorating peripheral T-cell lymphoma by decreasing regulatory T cells and increasing CD8+ T cells.The pharmaceutical composition of the present invention may exhibit anticancer activity against peripheral T-cell lymphoma by decreasing regulatory T cells which suppress immune responses and increasing CD8+ T cells which exhibit anticancer activity. In addition, the pharmaceutical composition of the present invention may be used for the treatment of peripheral T-cell lymphoma due to excellent safety and tolerability.

CHIMERIC ANTIGEN RECEPTORS SPECIFIC FOR B-CELL MATURATION ANTIGEN FOR USE IN TREATING MYELOMA

Resumen de: WO2023081735A1

Provided herein are adoptive cell therapy methods involving the administration of genetically engineered cells for treating disease and conditions, including certain plasma cell malignancy. The cells generally express recombinant receptors such as chimeric antigen receptors (CARs) specific to B-cell maturation antigen (BCMA). In some embodiments, the methods are for selecting and treating subjects with multiple myeloma (MM).

ASSOCIATION OF T CELL LEUKEMIA/LYMPHOMA PROTEIN 1A (TCL1A) WITH CLONAL HEMATOPOIESIS OF INDETERMINATE POTENTIAL (CHIP)

Resumen de: MX2024005298A

Methods of treating subjects having clonal hematopoiesis of indeterminate potential (CHIP) with T Cell Leukemia/Lymphoma Protein 1A (TCL1A) antagonists, and methods of identifying subjects having an increased or decreased risk of developing CHIP are provided herein.

BCMA-TARGETED CAR-T CELL THERAPY FOR MULTIPLE MYELOMA

Resumen de: MX2024005461A

Provided herein are methods of treating a subject who has multiple myeloma and has received prior treatment and has limited treatment options. Infusions of chimeric antigen receptor (CAR)-T cells comprising an anti-BCMA CAR comprising a polypeptide are administered to the subject. In certain embodiments, the dose of CAR-T cells administered to the subject is from 1.0 x 10⁵ to 5.0 x 10⁶ of CAR-T cells per kilogram of the subject's mass. The method of treatment is effective in obtaining and maintaining minimal residual disease negativity status, as well as other beneficial clinical outcomes related to efficacy and safety.

ASYMMETRIC BISPECIFIC ANTIBODY (UMG2/CD1A-CD3?) FOR THE IMMUNOLOGICAL TREATMENT OF CORTICAL-DERIVED CD1A-EXPRESSING T-CELL ACUTE LYMPHOBLASTIC LEUKEMIAS (T-ALL)

Resumen de: WO2023079425A1

Asymmetric bispecific antibody (UMG2/CD1a-CD3ε for the immunological treatment of cortical-derived CD1a-expressing T-cell acute lymphoblastic leukemias (T-ALL), against which said antibody specifically recruit, activate and redirect normal T-cells Use of the asymmetric bispecific antibody (UMG2/CD1a-CD3ε) for the immunological treatment of cortical-derived CD1a-expressing T-cell acute lymphoblastic leukemias (T-ALL and/or for the immunological treatment of Langherans histiocytosis.

DESIGNER RECOMBINASE FOR THE PRECISE EXCISION OF HTLV-1-PROVIRUS

Resumen de: WO2024180092A1

The present invention relates to a nucleic acid encoding a recombinase capable of recombining asymmetric target sequences of SEQ ID NO:1 within the long terminal repeat of proviral DNA of a plurality of HTLV-1 strains, the recombinase having specific amino acid exchanges compared to the sequence of cre recombinase. The invention also provides expression vectors comprising said nucleic acids and cells comprising the same, the recombinase in protein form and pharmaceutical compositions comprising them. A method for provision of such recombinases is also provided. The invention also provides a method of treating a HTLV-1-infected subject, wherein the subject optionally has adult T-cell leukemia (ATL) and/or HTLV-1-associated myelopathy (HAM).

CRYSTAL FORM OF PIRTOBRUTINIB, PREPARATION METHOD THEREFOR AND USE THEREOF

Resumen de: WO2024179558A1

The present invention relates to a novel crystal form of pirtobrutinib, a preparation method therefor, a pharmaceutical composition containing said crystal form, and use of the crystal form in the preparation of an oral non-covalent BTK inhibitor drug and a drug for treating cellular lymphoma, chronic lymphocytic leukemia and small lymphocytic lymphoma.

METHOD FOR THE SYNTHESIS OF THE ACTIVE PHARMACEUTICAL INGREDIENT, LENALIDOMIDE, AS AN ANTICANCER DRUG, AND ITS KEY INTERMEDIATES

Resumen de: WO2024180370A1

Lenalidomide is prescribed for the treatment of patients with malignant tumors and myelodysplastic syndrome. In the present invention, the synthesis technology of key intermediate (S,R)-3-(7-Nitro-3-oxo-1H-isoindole-2-yl)piperidine-2,6-dione and the active pharmaceutical ingredient of lenalidomide was optimized and customized. By carefully evaluating the current synthetic routes, a convenient, practical and cost- effective method for the synthesis of (R,S)-3-(7-nitro-3-oxo-1H-isoindol-2-yl)pyridine- 6,2- Dione as a key intermediate and lenalidomide as an active ingredient were used. At the same time, upon the recrystallization process, the separation and purification steps of the final product were greatly facilitated, and multiple steps of filtration using activated carbon were replaced and filtration device was eliminated, and product waste was reduced in this step. The final washing process of the product obtained according to the optimal method in this invention removed all the impurities and turned the color of the final product into a milky color according to the commercial sample.

DUAL-TARGET CAR-T HAVING OPTIMIZED ITAM DOMAIN AND CD28 AND 4-1BB DUAL COSTIMULATORY MOLECULES

Resumen de: WO2024179518A1

A dual-target CAR-T having an optimized ITAM domain and CD28 and 4-1BB dual costimulatory molecules. By respectively using CD28 and 4-1BB as costimulatory domains, a dual-target CAR-T targeting CD22 and CXCR5 antigens is constructed, and by calibrating the number of activated ITAM sites in CD3ζ, the synergistic costimulatory effect of CD28 and 4-1BB is optimized, thereby improving the persistent activity of CAR-T and overcoming poor therapeutic effect or tumor recurrence caused by antigen escape. The dual-target CAR-T cell can more effectively kill B lymphoma cells, and has persistent activity. Therefore, the present invention has the prospect of being applied in the field of tumor treatment.

COMBINATION DRUG CONTAINING CD20/CD47 BLOCKING BIFUNCTIONAL FUSION PROTEIN, AND USE THEREOF

Resumen de: WO2024179545A1

Provided are a method for treating cancers by using a CD20/CD47 double-blocking bifunctional fusion protein and a bifunctional alkylating agent in combination, and a use, in particular a method for treating cancers (especially non-Hodgkin lymphoma) by using a CD20/CD47 double-blocking bifunctional fusion protein and bendamustine or a salt thereof in combination, and a use.

METHODS AND COMPOSITIONS FOR INHIBITION OF DIHYDROOROTATE DEHYDROGENASE

Resumen de: US2024294477A1

Disclosed herein are compounds, 3,4,6,8-substituted-2-(1,1′-biphenyl-4-yl)quinoline analogs, that are inhibitors of dihydroorotate dehydrogenase (DHODH) with improved pharmacokinetic properties. The disclosed compounds can be used in the treatment of a variety of disorders and diseases in which inhibition of DHODH can be clinically useful, including cancer, such as a hematological cancer, including acute myeloid leukemia (AML); graft-versus-host-diseases; autoimmune disorders; and disorders associated with T-cell proliferation. The disclosed compounds can demonstrate flip-flop kinetics when administered orally, i.e., pharmacokinetics in which the rate of absorption, rather than the rate of elimination, dominates the pharmacokinetics. The disclosed compounds can demonstrate a sustained pharmacokinetic profile instead of an immediate release profile. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present disclosure.

Methods of treating myelodysplastic syndrome

Resumen de: AU2024208794A1

Methods of monitoring therapeutic efficacy in a subject with MDS are provided. Also provided is a method of identifying a subject with myelodysplastic syndrome (MDS) for treatment with a telomerase inhibitor, and methods of treating MDS. The subject methods can include administering to the subject an effective amount of a telomerase inhibitor and assessing the hTERT expression levels in a biological sample obtained from the subject. In some cases, a 50% or greater reduction in hTERT expression level identifies a subject who has an increased likelihood of benefiting from treatment with the telomerase inhibitor. The subject can be naive to treatment with a HMA, lenalidomide, or both. In some cases, the subject is classified as having low or intermediate-i IPSS risk MDS and/or MDS relapsed/refractory to Erythropoiesis Stimulating Agent (ESA). In some instances, the telomerase inhibitor is imetelstat sodium.

XBP1, CD138, and CS1 peptides, pharmaceutical compositions that include the peptides, and methods of using such peptides and compositions

Resumen de: AU2024205851A1

The disclosure features, inter alia, immunogenic XBP1-, CD138-, and CS1-derived peptides (and pharmaceutical compositions thereof). The peptides can be used in a variety of methods such as methods for inducing an immune response, methods for producing an antibody, and methods for treating a cancer (e.g., breast cancer, colon cancer, pancreatic cancer, a blood cancer, e.g., leukemia or a plasma cell disorder such as multiple myeloma or Waldenstrom's macroglobulinemia). The peptides (and pharmaceutical compositions comprising the peptides) can be used, e.g., in a method of treating a precancerous condition such as smoldering multiple myeloma. The peptides can also be included in MHC molecule multimer compositions and used in, e.g., methods for detecting a T cell in a population of cells.

HUMANIZED CD1a TARGETING MOIETY FOR THE TREATMENT OF CD1A-POSITIVE CANCER

Resumen de: AU2023225164A1

Relapsed/refractory T-cell acute lymphoblastic leukemia (T-ALL) has a dismal outcome, and no effective targeted immunotherapies for T-ALL exist. CD1a is exclusively expressed in cortical T-ALLs, a major subset of T-ALL. The expression of CD1a is restricted to cortical thymocytes and neither CD34+ progenitors nor T-cells express CD1a during ontogeny, confining the risk of on-target/off-tumor toxicity. The present invention provides CD1a-targeting moieties comprising a CD1a-which may be placed into T cells. The resultant CARTs are suitable for the treatment of cortical T-ALLs.

ANTIBODIES BINDING BCMA AND CD3 AND USES THEREOF

Resumen de: AU2023260205A1

Disclosed is a monoclonal antibody that specifically binds BCMA, or an antigen binding fragment thereof, and its use in treating cancers such as multiple myeloma. Also disclosed is a monoclonal antibody that specifically binds CD3, or an antigen binding fragment thereof, and its use in treating or alleviating an inflammatory disease, an autoimmune disease, or transplantation rejection. Further disclosed is an anti-BCMA/CD3 bispecific antibody, and its use in treating diseases such as cancers.

MULTI-CYCLIC IRAK AND FLT3 INHIBITING COMPOUNDS AND USES THEREOF

Resumen de: US2024294530A1

Some embodiments of the disclosure include inventive compounds (e.g., compounds of Formula (I)) and compositions (e.g., pharmaceutical compositions) which inhibit IRAK and/or FLT3 and which can be used for treating, for example, certain diseases. Some embodiments include methods of using the inventive compound (e.g., in compositions or in pharmaceutical compositions) for administering and treating (e.g., diseases such as hematopoietic cancers, myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), etc.), Additional embodiments provide disease treatment using combinations of the inventive IRAK and/or FLT3 inhibiting compounds with other therapies, such as cancer therapies.

PROTEOLYSIS TARGETING CHIMERAS AND METHODS OF USE THEREOF

Resumen de: US2024293557A1

Proteolysis-targeting chimeras (PROTACs) that indirectly inhibit Myeloid Cell Leukemia-1 (Mcl-1) oncoprotein, and methods of using the same, are provided for treating disease.

METHODS FOR TREATING AND AMELIORATING T CELL RELATED DISEASES

Resumen de: US2024293365A1

In alternative embodiments, provided are methods for treating or ameliorating hyperactive ZAP70 kinase-related diseases or conditions, including any disease or conditions mediated by hyperactive T cells or disease or condition whose pathology is initiated, aggravated or mediated by hyperactive T cells, such as autoimmune disease (including for example, an autoimmune disease requiring allogeneic hematopoietic cell transplantation (HCT) in patients, rheumatoid arthritis (RA), inflammatory bowel disease (IBD), Crohn's disease, type 1 diabetes, multiple sclerosis, uncontrollable bullous pemphigoid, colitis, celiac disease, dermatitis and proteinuria), organ transplant rejection, graft-versus-host disease (GVHD) and/or B cell chronic lymphocytic leukemia (CLL). In alternative embodiments, methods as provided herein comprise administering to an individual in need thereof the FDA-approved cancer drug sunitinib (or SUTENT™), or salts or formulations thereof, for example sunitinib malate.

PHARMACEUTICAL COMPOSITIONS OF 3-(4-AMINO-1-OXO-1, 3 DIHYDRO-ISOINDOL-2-YL)-PIPERIDINE-2, 6-DIONE

Nº publicación: US2024293312A1 05/09/2024

Solicitante:

RISHABH SHAH [IN]
BHAVESH BHAVSAR [US]
RISHABH Shah,
BHAVESH Bhavsar