# US 9,950,025 B2 · Compositions and methods for treatment of neoplastic disease > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 9,950,025 B2 - Document ID: US9950025B2 - Status: Granted - Kind: B2 - Application number: 15/237,594 - Filed: 2016-08-15 - Published: 2016-12-08 - Granted: 2018-04-24 - Earliest claimed: 2008-04-01 - Assignees: Innate Immunotherapeutics Limited - Applicants: Innate Immunotherapeutics Limited - Inventors: Frank B. Gelder; Gillian Alison Webster - Web page: https://patentgrep.com/patent/US9950025B2 ## CPC - A61K 38/05: Dipeptides - A61K 9/14: Particulate form, e.g. powders, {Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles (microspheres A61K9/16; microcapsules A61K9/50; nanocapsules, nanoparticles of the matrix type A61K9/51)} - A61K 31/337: having four-membered rings, e.g. taxol - A61K 31/738: Cross-linked polysaccharides - A61K 39/385: Haptens or antigens, bound to carriers - A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca - A61K 47/646: {the entire peptide or protein drug conjugate elicits an immune response, e.g. conjugate vaccines} - A61P 35/00: Antineoplastic agents - A61P 35/04: specific for metastasis - A61K 2039/6062: {Muramyl peptides} - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## Abstract The present invention is concerned with immunostimulant compositions, in particular compositions comprising microparticulate form of muramyl dipeptide, and their use in the treatment of neoplastic disease. ## Claims ### Claim 1 A method of treating neoplastic disease comprising administering to a subject requiring such treatment an effective amount of muramyl dipeptide cross-linked into a microparticle (MDP-microparticle). ### Claim 2 (depends on 1) The method according to claim 1, wherein the MDP-microparticle is combined with at least one immunostimulatory ligand, bound to or within the microparticle, which is capable of stimulating immune cell subsets effective in inhibiting tumour cell growth and/or proliferation, or effective in tumour cell damage and/or destruction. ### Claim 3 (depends on 2) The method according to claim 2, wherein the immunostimulatory ligand is selected from one or more molecular pattern recognition receptor families or is an immunostimulatory glycolipid antigen. ### Claim 4 (depends on 3) The method according to claim 3, wherein the molecular pattern recognition receptor ligand is selected from one or more of TLR1,2,3,4,5,6,7,8,9,10, NOD-1 and NOD-2 and the glycolipid antigen is α-GalCer or an analogue thereof. ### Claim 5 (depends on 2) The method according to claim 2, wherein the immunostimulatory ligand is cross-linked on the surface or within the MDP-microparticle. ### Claim 6 (depends on 1) The method according to claim 1, wherein the MDP-microparticle has an overlapping immunostimulatory effect with that induced by interleukin-2 (IL-2). ### Claim 7 (depends on 1) The method according to claim 1, wherein the MDP-microparticle stimulates the production of anti-neoplastic cytokines selected from interferon-alpha (IFNα), interferon-gamma (IFNγ), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin 12 (IL-12) and TNFα. ### Claim 8 (depends on 1) The method according to claim 1, wherein the neoplastic disease is selected from carcinoma, sarcoma, myeloma, leukaemia, lymphoma or a mixed-type. ### Claim 9 (depends on 1) The method according to claim 1, wherein, the neoplastic disease is selected from fibrosarcoma, myxosarcoma, liposarcoma, chondrosarcoma, osteosarcoma, chordoma, malignant fibrous histiocytoma, hemangiosarcoma, angiosarcoma, lymphangiosarcoma, mesothelioma, acute myelogenous leukaemia, acute lymphoblastic leukaemia, chronic myelogenous leukaemia, chronic lymphoblastic leukaemia, plasmacytoma, multiple myeloma, Hodgkin lymphoma and non-Hodgkin lymphoma, rhabdomyosarcoma, leiomyosarcoma, squamous cell carcinoma, epidermoid carcinoma, adenocarcinoma, hepatocellular carcinoma, renal cell carcinoma, hypernephroma, cholangiocarcinoma, transitional cell carcinoma, choriocarcinoma, seminoma, embryonal cell carcinoma, glioma, anaplastic glioblastoma multiforme, neuroblastoma, medulloblastoma, malignant meningioma, malignant meningioma, malignant schwannoma, neurofibrosarcoma, parathyroid carcinoma, medullary carcinoma of thyroid, bronchial carcinoid, oat cell carcinoma, malignant pheochromocytoma, islet cell carcinoma, malignant carcinoid, malignant paraganglioma, melanoma, malignant schwannoma, merkel cell neoplasm, cystosarcoma phylloides, Wilms' tumour, dysgerminoma, retinoblastoma and teratocarcinoma. ### Claim 10 (depends on 1) The method according to claim 1, further comprising administering one or more other anti-neoplastic agents for the treatment of neoplastic disease. ### Claim 11 (depends on 10) The method according to claim 10, wherein the other anti-neoplastic agent is selected from an alkylating agent; an antimetabolite; an alkaloid; a type I or type II topoisomerase inhibitors; an antibiotic; a hormone; and a cytokine. ### Claim 12 (depends on 1) The method according to claim 1, wherein the subject has metastases. ### Claim 13 (depends on 1) The method according to claim 1, wherein the MDP-microparticle stimulates release of cytokines, chemokines and cytotoxic proteins in the subject. ### Claim 14 (depends on 13) The method according to claim 13, wherein the cytokines, chemokines and cytotoxic proteins are selected from IL-2, IFNγ, IFNα, GM-CSF, TNFα, TRAIL and FasL. ### Claim 15 (depends on 1) The method according to claim 1, wherein the MDP-microparticle stimulates secretion of IFNα from peripheral blood plasmocytoid dendritic cells (pDCs). ### Claim 16 (depends on 1) The method according to claim 1, wherein the MDP-microparticle stimulates secretion of TNFα from monocytes. ### Claim 17 (depends on 1) The method according to claim 1, wherein the MDP-microparticle is administered in combination with one or more tumour-associated antigens, bound to or within the MDP-microparticle, capable of stimulating a tumour specific immune response. ### Claim 18 (depends on 17) The method according to claim 17, wherein the tumour-associated antigen is selected from autologous tumour cells, CEA, CA19-9, CA125, EP-CAM, her-2/neu, melanoma antigen and GM2. ### Claim 19 (depends on 11) The method according to claim 11, wherein the alkylating agent is selected from the group consisting of cisplatin, carboplatin, busulfan, chlorambucil and carmustine. ### Claim 20 (depends on 11) The method according to claim 11, wherein the antimetabolite is selected from the group consisting of azathioprine and mercaptopurine. ### Claim 21 (depends on 11) The method according to claim 11, wherein the alkaloid is selected from the group consisting of vincristine, vinblastine, vinorelbine, vindesine, podophyllotoxin and taxol. ### Claim 22 (depends on 11) The method according to claim 11, wherein the antibiotic is selected from the group consisting of dactinomycin, bleomycin and doxorubicin. ### Claim 23 (depends on 11) The method according to claim 11, wherein the cytokine is selected from the group consisting of IL-2, IFNγ, GM-CSF, TNFα or IFN-α.