公开(公告)号：US20240293465A1

公开(公告)日：2024-09-05

申请号：US18531118

申请日：2023-12-06

Applicant: Omeros Corporation ,  University of Leicester

Inventor： Gregory A. Demopulos ,  Thomas Dudler ,  Hans-Wilhelm Schwaeble

IPC: A61K35/28 ,  A01K67/0276 ,  A61K9/00 ,  A61K39/00 ,  A61P7/02 ,  A61P37/06 ,  A61P39/00 ,  C07K16/40 ,  C12N9/64

CPC classification number: A61K35/28 ,  A01K67/0276 ,  A61K9/0019 ,  A61P7/02 ,  A61P39/00 ,  C07K16/40 ,  C12N9/6424 ,  C12Y304/21104 ,  A01K2217/075 ,  A01K2227/105 ,  A01K2267/0381 ,  A01K2267/0387 ,  A61K2039/505 ,  A61P37/06 ,  C07K2317/24 ,  C07K2317/33 ,  C07K2317/54 ,  C07K2317/55 ,  C07K2317/565 ,  C07K2317/622 ,  C07K2317/76 ,  C07K2317/92

Abstract: In one aspect, the invention provides methods of inhibiting the effects of MASP-2-dependent complement activation in a human subject suffering from graft-versus-host disease and/or diffuse alveolar hemorrhage and/or veno-occlusive disease associated with a hematopoietic stem cell transplant. The methods comprise the step of administering, to a subject in need thereof, an amount of a MASP-2 inhibitory agent effective to inhibit MASP-2-dependent complement activation.

公开(公告)号：US20240276958A1

公开(公告)日：2024-08-22

申请号：US18646802

申请日：2024-04-26

Applicant: Yunnan Agricultural University

Inventor： Hong-jiang Wei ,  Qing-feng Chen ,  Heng Zhao ,  De-ling Jiao ,  Hong-ye Zhao

IPC: A01K67/0276 ,  C07K14/715 ,  C12N9/22 ,  C12N15/11 ,  C12N15/90 ,  C12Q1/6883

CPC classification number: A01K67/0276 ,  C12N9/22 ,  C12N15/11 ,  C12N15/907 ,  C12Q1/6883 ,  A01K2217/15 ,  A01K2227/108 ,  A01K2267/0387 ,  C07K14/7155 ,  C12Q2600/124

Abstract: The present disclosure relates to a sgRNA and constructing a dual pig model of severe immunodeficiency and liver injury and use thereof. The method comprises the steps of knocking out RAG2, IL2Rγ and FAH genes in a porcine fetal fibroblast by using a CRISPR/Cas9 technology, constructing a RAG2−/−/IL2Rγ−/Y/FAH−/− triple-gene edited cloned pig by using a somatic cell nuclear transfer technology, and obtaining a dual pig model of severe immunodeficiency and liver injury through phenotypic analysis and identification. The method overcomes the problems of long production period, low efficiency, irreversible damage, unsatisfactory use in a humanization degree and the like in the existing model construction technology, can realize a batch construction of the dual pig model of severe immunodeficiency and liver injury by a continuous cloning technology, and has great advantages and potential market application prospects in the related fields of tumor biology, cell transplantation, humanized animal models and the like.

公开(公告)号：US11980629B2

公开(公告)日：2024-05-14

申请号：US17399871

申请日：2021-08-11

Applicant: CITY OF HOPE

Inventor： Defu Zeng

IPC: A61K31/675 ,  A61K31/7056 ,  A61K35/14 ,  A61K35/17 ,  A61K35/26 ,  A61K35/28 ,  A61K39/395 ,  A61P37/06 ,  C07K16/28

CPC classification number: A61K31/675 ,  A61K31/7056 ,  A61K35/14 ,  A61K35/17 ,  A61K35/26 ,  A61K35/28 ,  A61K39/39516 ,  A61P37/06 ,  C07K16/2809 ,  A01K2207/20 ,  A01K2227/105 ,  A01K2267/0387 ,  A61K31/7056 ,  A61K2300/00 ,  A61K31/675 ,  A61K2300/00

Abstract: Disclosed herein are conditioning regimens and methods for inducing MHC- or HLA-mismatched mixed chimerism by conditioning a recipient with radiation-free, low-doses of cyclophosphamide (CY), pentostatin (PT), and anti-thymocyte globulin (ATG) prior to transplantation of donor bone marrow cells. In certain embodiments, the donor bone marrow cells may be CD4+ T-depleted bone marrow cells. The conditioning regimens and methods may also include administering one or more populations of conditioning donor cells selected from donor CD4+ T-depleted spleen cells, donor CD8+ T cells, and donor G-CSF-mobilized peripheral blood mononuclear cells. The conditioning regimen is clinically acceptable and can be used for treating hereditary hematological diseases and autoimmune diseases, as well as for promoting organ transplantation immune tolerance.

公开(公告)号：US20240008460A1

公开(公告)日：2024-01-11

申请号：US18034995

申请日：2021-10-15

Applicant: KOREA RESEARCH INSTITUTE OF BIOSCIENCE AND BIOTECHNOLOGY

Inventor： Sun Uk KIM ,  Young Ho PARK ,  Bo Woong SIM ,  Kyu Tae CHANG ,  Seung Hwan LEE ,  Bong Seok SONG ,  Pil Soo JEONG ,  Hae Jun YANG ,  Sang Rae LEE ,  Yeung Bae JIN ,  Kang Jin JEONG

IPC: A01K67/027 ,  C12N9/22 ,  C12N15/11 ,  C12N15/90

CPC classification number: A01K67/0276 ,  C12N9/22 ,  C12N15/11 ,  C12N15/907 ,  A01K2227/108 ,  A01K2217/075 ,  A01K2217/054 ,  A01K2267/0387 ,  C12N2310/20

Abstract: The present disclosure relates to a JAK3 gene-mutated severe combined immunodeficiency animal model and a method of constructing the same. In the JAK3 gene-mutated severe combined immunodeficiency animal model of the present disclosure, the JAK3 gene is specifically deficient, the expression of cytokines is regulated by controlling the number and activity of macrophages, and the thymus, lymphocytes, and Peyer's patches, which are observed in conventional severe combined immunodeficiency animal models, particularly mini-pigs, are completely lacking. In addition, the animal model of the present disclosure can be used as a treatment model for JAK3 SCID patients, as similar phenotypes are observed in patients with human severe combined immunodeficiency caused by a JAK3 gene mutation, and can be used for artificial blood development or xenotransplantation.

公开(公告)号：US20230389531A1

公开(公告)日：2023-12-07

申请号：US18327976

申请日：2023-06-02

Applicant: The Jackson Laboratory

Inventor： David V. Serreze ,  Jeremy J. Racine

IPC: A01K67/027 ,  A61K49/00 ,  C12N15/85

CPC classification number: A01K67/0276 ,  A61K49/0008 ,  C12N15/8509 ,  A01K2217/075 ,  C12N2015/8563 ,  A01K2267/0325 ,  A01K2267/0362 ,  A01K2267/0387 ,  A01K2227/105

Abstract: The present disclosure relates to genetically modified non-obese diabetic (NOD) mice deficient in murine class I MHC molecules, class II molecules, or both class I and class II MHC molecules. The MHC knockout transgenic mice provided herein are useful, for example, for developing therapies for diabetes.

公开(公告)号：US20230270085A1

公开(公告)日：2023-08-31

申请号：US18015043

申请日：2021-07-07

Applicant: The Jackson Laboratory

Inventor： Anna Karolina Palucka ,  Chu l. Yu ,  Jacques Banchereau ,  Richard Maser ,  Leonard D. Shultz

IPC: A01K67/027 ,  C07K14/54 ,  C07K14/535 ,  C07K14/74 ,  C12N15/85

CPC classification number: A01K67/0275 ,  C07K14/5403 ,  C07K14/535 ,  C07K14/70539 ,  C12N15/8509 ,  A01K2207/15 ,  A01K2217/075 ,  A01K2227/105 ,  A01K2267/0362 ,  A01K2267/0387 ,  A01K2217/072

Abstract: The present disclosure provides an immunodeficient NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ (NSG™) mouse models that comprise an inactivated mouse Flt3 allele, a nucleic acid encoding human interleukin 3 (IL3), a nucleic acid encoding human granulocyte/macrophage-stimulating factor (GM-CSF), a nucleic acid encoding human stem cell factor (SCF), and a HLA-A2/H2-D/B2M transgene encoding (i) a human B2-microglubulin (B2M) covalently linked to MHC class 1, alpha 1, and alpha2 binding domains of a human HLA-A2.1 gene and (ii) alpha3 cytoplasmic and transmembrane domains of murine H2-db.

公开(公告)号：US11712026B2

公开(公告)日：2023-08-01

申请号：US16163334

申请日：2018-10-17

Applicant: The Jackson Laboratory

Inventor： David V. Serreze ,  Jeremy J. Racine

IPC: A01K67/027 ,  A61K49/00 ,  C12N15/85

CPC classification number: A01K67/0276 ,  A61K49/0008 ,  C12N15/8509 ,  A01K2217/075 ,  A01K2227/105 ,  A01K2267/0325 ,  A01K2267/0362 ,  A01K2267/0387 ,  C12N2015/8563

Abstract: The present disclosure relates to genetically modified non-obese diabetic (NOD) mice deficient in murine class I MHC molecules, class II molecules, or both class I and class II MHC molecules. The MHC knockout transgenic mice provided herein are useful, for example, for developing therapies for diabetes.

公开(公告)号：US20230189772A1

公开(公告)日：2023-06-22

申请号：US18047014

申请日：2022-10-17

Applicant: Regeneron Pharmaceuticals, Inc.

Inventor： Jose F. Rojas ,  Ka-Man Venus Lai ,  Andrew J. Murphy ,  Cagan Gurer

IPC: A01K67/027 ,  C12N15/85 ,  C07K14/54

CPC classification number: A01K67/0278 ,  C12N15/8509 ,  C07K14/5443 ,  A01K2227/10 ,  A01K2217/072 ,  A01K2217/07 ,  C12N2015/8527 ,  A01K2207/15 ,  A01K2267/03 ,  A01K2267/0387 ,  A01K2227/105

Abstract: Genetically modified non-human animals comprising a humanized interleukin-15 (IL-15) gene. Cells, embryos, and non-human animals comprising a human IL-15 gene. Rodents that express humanized or human IL-15 protein.

公开(公告)号：US20180066318A1

公开(公告)日：2018-03-08

申请号：US15554424

申请日：2016-03-04

Applicant: INSTITUT PASTEUR ,  UNIVERSITE PARIS DIDEROT - PARIS 7

Inventor： Robert WEIL ,  Nassima MESSALI ,  Helena SOARES ,  Satoh-Takayama NAOKO ,  Andromahi TRIVELLAS ,  James DI SANTO ,  Andrés ALCOVER

IPC: C12Q1/68 ,  G01N33/574 ,  A01K67/027

CPC classification number: C12Q1/6886 ,  A01K67/0276 ,  A01K2217/075 ,  A01K2217/077 ,  A01K2227/105 ,  A01K2267/0387 ,  C12Q2600/118 ,  C12Q2600/136 ,  C12Q2600/156 ,  G01N33/57407 ,  G01N2500/10

Abstract: The invention provides methods of identifying an E-SYT2 modulator. The methods may comprise providing a cell that expresses E-SYT2; contacting the cell with a candidate chemical entity; and characterizing recruitment of at least one of Carma1, BcllO, NEMO, and PKC9 to the immunological synapse (IS). The invention also provides E-SYT2 modulators, including inhibitors, identified using the disclosed methods. The invention provides methods of inhibiting NF-κB activity in a cell comprising contacting the cell with an E-SYT2 inhibitor. The invention provides methods comprising providing a sample from a patient suspected of having or at risk of having a MALT-lymphoma or an ABC-DLBCL-lymphoma; and screening the sample to identify the presence and/or absence of a gain of function E-Syt2 mutation in the sample. The invention also provides genetically modified mammals comprising one or two loss of function alleles of E-Syt2.

公开(公告)号：US20180064786A1

公开(公告)日：2018-03-08

申请号：US15812342

申请日：2017-11-14

Applicant: YALE UNIVERSITY

Inventor： Demetrios BRADDOCK ,  Ronald ALBRIGHT

IPC: A61K38/17 ,  A61K48/00 ,  C12N15/52 ,  C12N15/62 ,  C12N15/85 ,  C12N9/96 ,  C07K7/06 ,  A61K38/04 ,  C12Q1/68

CPC classification number: A61K38/1741 ,  A01K67/0271 ,  A01K2207/15 ,  A01K2207/20 ,  A01K2227/105 ,  A01K2267/0387 ,  A61K38/02 ,  A61K38/04 ,  A61K38/46 ,  A61K38/465 ,  A61K48/0058 ,  A61P9/10 ,  A61P13/12 ,  C07K7/06 ,  C07K14/745 ,  C07K2319/01 ,  C07K2319/30 ,  C07K2319/31 ,  C07K2319/33 ,  C07K2319/70 ,  C12N9/96 ,  C12N15/52 ,  C12N15/625 ,  C12N15/85 ,  C12N2840/007 ,  C12Q1/6883 ,  C12Y301/04001 ,  C12Y306/01009 ,  H05K999/99

Abstract: The present invention includes compositions and methods for treating diseases or disorders associated with pathological calcification or pathological ossification. In certain embodiments, the diseases or disorders are selected from the group consisting of Generalized Arterial Calcification of Infancy (GACI), Idiopathic Infantile Arterial Calcification (IIAC), Ossification of the Posterior Longitudinal Ligament (OPLL), hypophosphatemic rickets, osteoarthritis, calcification of atherosclerotic plaques, PXE, hereditary and non-hereditary forms of osteoarthritis, ankylosing spondylitis, hardening of the arteries occurring with aging, calciphylaxis resulting from end stage renal disease and progeria.