公开(公告)号：US20230159617A1

公开(公告)日：2023-05-25

申请号：US17861954

申请日：2022-07-11

Applicant: THE REGENTS OF THE UNIVERSITY OF COLORADO, A BODY CORPORATE

Inventor： Brian Freed ,  Christina Roark ,  Elizabeth Sunderhaus

IPC: C07K14/74

CPC classification number: C07K14/70539

Abstract: Methods of preventing or treating autoimmune disease are disclosed. In some cases, subjects with having or at risk of developing autoimmune disease are identified as possessing one or more autoimmunity-susceptibility HLA alleles at one or more HLA loci. In many cases, the HLA loci are selected from Class I and Class II loci, for example Class I A, B, and C, and Class II DQ, DR, and DP. In many cases, subjects suffering from or at risk of developing an autoimmune disease may be administered a plurality engineered autologous HSCs modified to carry and express a variant susceptibility allele having at least one mutation in the antigen binding cleft that alters antigen binding and/or specificity of that variant HLA molecule. In many embodiments, the engineered HSCs are CD34+ immune cells that express one or more modified HLA proteins.

公开(公告)号：US20230126183A1

公开(公告)日：2023-04-27

申请号：US17861943

申请日：2022-07-11

Applicant: THE REGENTS OF THE UNIVERSITY OF COLORADO, A BODY CORPORATE

Inventor： Brian Freed ,  Christina Roark ,  Elizabeth Sunderhaus

IPC: C07K14/74 ,  A61P37/02

Abstract: Methods of preventing or treating autoimmune disease are disclosed. In some cases, subjects with having or at risk of developing autoimmune disease are identified as possessing one or more autoimmunity-susceptibility HLA alleles at one or more HLA loci. In many cases, the HLA loci are selected from Class I and Class II loci, for example Class I A, B, and C, and Class II DQ, DR, and DP. In many cases, subjects suffering from or at risk of developing an autoimmune disease may be administered a plurality engineered autologous HSCs modified to carry and express a variant susceptibility allele having at least one mutation in the antigen binding cleft that alters antigen binding and/or specificity of that variant HLA molecule. In many embodiments, the engineered HSCs are CD34+ immune cells that express one or more modified HLA proteins.

公开(公告)号：US20230091257A1

公开(公告)日：2023-03-23

申请号：US17744554

申请日：2022-05-13

Applicant: THE REGENTS OF THE UNIVERSITY OF COLORADO, A BODY CORPORATE

Inventor： Brian Freed ,  Christina Roark ,  Elizabeth Sunderhaus

IPC: C07K14/74 ,  C12N15/62 ,  C12N15/86 ,  A61K35/17 ,  A61P37/06

Abstract: Methods of preventing or treating autoimmune disease are disclosed. In some cases, subjects with having or at risk of developing autoimmune disease are identified as possessing one or more autoimmunity-susceptibility HLA alleles at one or more HLA loci. In many cases, the HLA loci are selected from Class I and Class II loci, for example Class I A, B, and C, and Class II DQ, DR, and DP. In many cases, subjects suffering from or at risk of developing an autoimmune disease may be administered a plurality engineered autologous HSCs modified to carry and express a variant susceptibility allele having at least one mutation in the antigen binding cleft that alters antigen binding and/or specificity of that variant HLA molecule. In many embodiments, the engineered HSCs are CD34+ immune cells that express one or more modified HLA proteins.

公开(公告)号：US11932867B2

公开(公告)日：2024-03-19

申请号：US16609175

申请日：2018-04-25

Applicant: THE REGENTS OF THE UNIVERSITY OF COLORADO, A BODY CORPORATE

Inventor： Brian Freed ,  Kirsten Anderson ,  Christina Roark ,  Jennifer Matsuda

IPC: C12N15/85 ,  A61K35/28 ,  A61K48/00 ,  C12N5/0789 ,  C12N9/22 ,  C12N15/11

CPC classification number: C12N15/85 ,  A01K67/0275 ,  A61K35/28 ,  C12N5/0647 ,  C12N9/22 ,  C12N15/11 ,  A01K2217/05 ,  A01K2227/105 ,  A01K2267/0325 ,  A61K48/00 ,  C12N2310/20 ,  C12N2740/15042 ,  C12N2750/14142 ,  C12N2800/80

Abstract: Methods of preventing or treating rheumatoid arthritis (RA) in a subject by introducing the DRB1*04:01K71E mutation that is resistant to RA. The resistant allele is introduced into the subject having or at risk of developing RA, using a HLA CRISPR/Cas9 vector that targets codon 71 in the HLA allele DRB1*04:01, introducing a single A to G point mutation in codon 71 by homology directed repair to alter the lysine at position 71 of the expressed protein to glutamic acid. This modified allele is affected in the subject's hematopoietic stem cells, which are then expanded and transplanted back into the patient. This microgene therapy confers RA-resistance via an autologous transplant. The invention includes isolated nucleic acids, vectors, recombinant viruses, cells, and pharmaceutical compositions to modify the HLA DRB1*04:01 allele.

公开(公告)号：US20230295265A1

公开(公告)日：2023-09-21

申请号：US18156887

申请日：2023-01-19

Applicant: The Regents of The University of Colorado, A Body Corporate

Inventor： Brian Freed ,  Christina Roark ,  Elizabeth Sunderhaus

IPC: C07K14/74 ,  A61K35/17 ,  A61K35/28 ,  A61P37/06 ,  C12Q1/6881

CPC classification number: C07K14/70539 ,  A61K35/17 ,  A61K35/28 ,  A61P37/06 ,  C12Q1/6881

Abstract: Methods of preventing or treating autoimmune disease are disclosed. In some cases, subjects with having or at risk of developing autoimmune disease are identified as possessing one or more autoimmunity-susceptibility HLA alleles at one or more HLA loci. In many cases, the HLA loci are selected from Class I and Class II loci, for example Class I A, B, and C, and Class II DQ, DR, and DP. In many cases, subjects suffering from or at risk of developing an autoimmune disease may be administered a plurality engineered autologous HSCs modified to carry and express a variant susceptibility allele having at least one mutation in the antigen binding cleft that alters antigen binding and/or specificity of that variant HLA molecule. In many embodiments, the engineered HSCs are CD34+ immune cells that express one or more modified HLA proteins.

公开(公告)号：US20230192808A1

公开(公告)日：2023-06-22

申请号：US17741438

申请日：2022-05-10

Applicant: THE REGENTS OF THE UNIVERSITY OF COLORADO, A BODY CORPORATE

Inventor： Brian Freed ,  Christina Roark ,  Elizabeth Sunderhaus

IPC: C07K14/74 ,  A61K35/17 ,  A61P37/06 ,  A61K35/28 ,  C12Q1/6881

CPC classification number: C07K14/70539 ,  A61K35/17 ,  A61P37/06 ,  A61K35/28 ,  C12Q1/6881

Abstract: Methods of preventing or treating autoimmune disease are disclosed. In some cases, subjects with having or at risk of developing autoimmune disease are identified as possessing one or more autoimmunity-susceptibility HLA alleles at one or more HLA loci. In many cases, the HLA loci are selected from Class I and Class II loci, for example Class I A, B, and C, and Class II DQ, DR, and DP. In many cases, subjects suffering from or at risk of developing an autoimmune disease may be administered a plurality engineered autologous HSCs modified to carry and express a variant susceptibility allele having at least one mutation in the antigen binding cleft that alters antigen binding and/or specificity of that variant HLA molecule. In many embodiments, the engineered HSCs are CD34+ immune cells that express one or more modified HLA proteins.

公开(公告)号：US12202880B2

公开(公告)日：2025-01-21

申请号：US17741438

申请日：2022-05-10

Applicant: THE REGENTS OF THE UNIVERSITY OF COLORADO

Inventor： Brian Freed ,  Christina Roark ,  Elizabeth Sunderhaus

IPC: C07K14/74 ,  A61K35/17 ,  A61K35/28 ,  A61K39/00 ,  A61P37/02 ,  A61P37/06 ,  C12N5/0775 ,  C12N15/62 ,  C12N15/86 ,  C12Q1/6881 ,  A61K38/00

Abstract: Methods of preventing or treating autoimmune disease are disclosed. In some cases, subjects with having or at risk of developing autoimmune disease are identified as possessing one or more autoimmunity-susceptibility HLA alleles at one or more HLA loci. In many cases, the HLA loci are selected from Class I and Class II loci, for example Class I A, B, and C, and Class II DQ, DR, and DP. In many cases, subjects suffering from or at risk of developing an autoimmune disease may be administered a plurality engineered autologous HSCs modified to carry and express a variant susceptibility allele having at least one mutation in the antigen binding cleft that alters antigen binding and/or specificity of that variant HLA molecule. In many embodiments, the engineered HSCs are CD34+ immune cells that express one or more modified HLA proteins.

公开(公告)号：US20240327862A1

公开(公告)日：2024-10-03

申请号：US18605149

申请日：2024-03-14

Applicant: THE REGENTS OF THE UNIVERSITY OF COLORADO, A BODY CORPORATE ,  NATIONAL JEWISH HEALTH

Inventor： Brian Freed ,  Kirsten Anderson ,  Christina Roark ,  Jennifer Matsuda

IPC: C12N15/85 ,  A01K67/0275 ,  A61K35/28 ,  A61K48/00 ,  C12N5/0789 ,  C12N9/22 ,  C12N15/11

CPC classification number: C12N15/85 ,  A01K67/0275 ,  A61K35/28 ,  C12N5/0647 ,  C12N9/22 ,  C12N15/11 ,  A01K2217/05 ,  A01K2227/105 ,  A01K2267/0325 ,  A61K48/00 ,  C12N2310/20 ,  C12N2740/15042 ,  C12N2750/14142 ,  C12N2800/80

Abstract: Methods of preventing or treating rheumatoid arthritis (RA) in a subject by introducing the DRB1*04:01K71E mutation that is resistant to RA. The resistant allele is introduced into the subject having or at risk of developing RA, using a HLA CRISPR/Cas9 vector that targets codon 71 in the HLA allele DRB1*04:01, introducing a single A to G point mutation in codon 71 by homology directed repair to alter the lysine at position 71 of the expressed protein to glutamic acid. This modified allele is affected in the subject's hematopoietic stem cells, which are then expanded and transplanted back into the patient. This microgene therapy confers RA-resistance via an autologous transplant. The invention includes isolated nucleic acids, vectors, recombinant viruses, cells, and pharmaceutical compositions to modify the HLA DRB1*04:01 allele.

公开(公告)号：US20230123094A1

公开(公告)日：2023-04-20

申请号：US17861914

申请日：2022-07-11

Applicant: THE REGENTS OF THE UNIVERSITY OF COLORADO, A BODY CORPORATE

Inventor： Brian Freed ,  Christina Roark ,  Elizabeth Sunderhaus

IPC: C12N5/0775 ,  C12N15/86 ,  C07K14/74

Abstract: Methods of preventing or treating autoimmune disease are disclosed. In some cases, subjects with having or at risk of developing autoimmune disease are identified as possessing one or more autoimmunity-susceptibility HLA alleles at one or more HLA loci. In many cases, the HLA loci are selected from Class I and Class II loci, for example Class I A, B, and C, and Class II DQ, DR, and DP. In many cases, subjects suffering from or at risk of developing an autoimmune disease may be administered a plurality engineered autologous HSCs modified to carry and express a variant susceptibility allele having at least one mutation in the antigen binding cleft that alters antigen binding and/or specificity of that variant HLA molecule. In many embodiments, the engineered HSCs are CD34+ immune cells that express one or more modified HLA proteins.