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EP0247494A2 Expired / Lapsed EP ⏱️ 0.0 years remaining

Evaluation of insulin expression

Assignee: General Hospital Corp
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Filing: 1987-05-19
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Granted: —
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Expires: 2007-05-19
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Abstract

Abstract A process for producing a transgenic mammal, especially a mouse which contains and expresses a hetero­logous gene, especially the human insulin hormone gene. The insulin gene is expressed only in the pancreas of the transgenic mouse and is regulated by glucose, glucagon, or other insulin affectors in a manner which is indistinguishable from that of normal mice. Progeny of the trangenic mice inherit the human insulin gene in a Mendelian manner, with approximately 50% of the mice of each litter expressing the human insulin gene. The weights of the transgenic mice, growth rate, feeding behavior, reproductive capability, and longevity appear indistinguishable from normal mice. The mice are useful for studies of pharmacokinetics of insulin expression and for investigations of possible drug interactions with glucose homeostasis.

Inventors

  • 👤 Richard F. Selden
  • 👤 Howard M. Prof. Goodman

Bibliographic Details

Application Number —
Jurisdiction EP
Data Source google_patents
Last Synchronized 2026-10-23 08:08
CPC Classifications
A; A01; A01K; A01K67/00; A01K67/027; A01K67/0275; A01K67/0278; C; C07; C07K; C07K14/00; C07K14/435; C07K14/575; C07K14/62; C12; C12N; C12N15/00; C12N15/09; C12N15/63; C12N15/79; C12N15/85; C12N15/8509; C12N15/87; C12N15/89; A01K2207/00; A01K2207/15; A01K2217/00; A01K2217/05; A01K2227/00; A01K2227/10; A01K2227/105; A01K2267/00; A01K2267/03; A01K2267/0306; A01K2267/0325

Claims Analysis

Total Claims: 13
Claim 1
Independent Claim 30 words
A mammal, preferably a rodent, especially a mouse whose cells contain the gene for human preproinsulin, pro­insulin or insulin and which is capable of producing progeny mammals carrying said gene.
Claim 2
Dependent Claim 30 words
A mammal, preferably a rodent, especially a mouse whose cells contain the gene for human preproinsulin, pro­insulin or insulin and which is capable of producing progeny mammals carrying said gene.
Claim 3
Dependent Claim 22 words
The mammal of claim 1, wherein said gene is stably expressed and preferably said expression of said human insulin is naturally regulated.
Claim 4
Independent Claim 172 words
A method for obtaining a target mammal whose cells contain a genetic sequence for all or part of the human preproinsulin, proinsulin or insulin genes and which is capable of being bred to produce progeny mammals whose cells contain said genetic sequences, comprising: (a) isolating a fertilized egg from a first female mammal; (b) transferring a genetic sequence which contains all or part of the human preproinsulin, proinsulin or insulin gene into said fertilized egg; (c) transferring said fertilized egg containing said genetic sequence to the uterus of a pseudopregnant second female mammal; (d) maintaining said second female mammal such that: (i) said second female mammal becomes pregnant with an embryo derived from said fertilized egg contain­ing said genetic sequence, (ii) said embryo develops into said target mammal, and (iii) said target mammal is viably born from said second female mammal; wherein said target mammal contains a genetic sequence for human preproinsulin, proinsulin or insulin and is capable of being bred to produce progeny mammals whose cells stably contain said genetic sequence.
Claim 5
Independent Claim 172 words
A method for obtaining a target mammal whose cells contain a genetic sequence for all or part of the human preproinsulin, proinsulin or insulin genes and which is capable of being bred to produce progeny mammals whose cells contain said genetic sequences, comprising: (a) isolating a fertilized egg from a first female mammal; (b) transferring a genetic sequence which contains all or part of the human preproinsulin, proinsulin or insulin gene into said fertilized egg; (c) transferring said fertilized egg containing said genetic sequence to the uterus of a pseudopregnant second female mammal; (d) maintaining said second female mammal such that: (i) said second female mammal becomes pregnant with an embryo derived from said fertilized egg contain­ing said genetic sequence, (ii) said embryo develops into said target mammal, and (iii) said target mammal is viably born from said second female mammal; wherein said target mammal contains a genetic sequence for human preproinsulin, proinsulin or insulin and is capable of being bred to produce progeny mammals whose cells stably contain said genetic sequence.
Claim 6
Dependent Claim 29 words
The method of claim 3, wherein said genetic sequence for human preproinsulin, proinsulin, or insulin is stably expressed and preferably said expression of said human insulin is naturally regulated.
Claim 7
Dependent Claim 20 words
The method of claim 3 or 4, wherein said first female mammal is a mouse, preferably of mouse strain C57/C3H.
Claim 8
Dependent Claim 25 words
The method of claim 3, 4 or 5, wherein said genetic sequence which is transferred into said fertilized egg is derived from plasmid pgHI 12.5.
Claim 9
Dependent Claim 10 words
The mammal of claim 1, which is mouse strain B6C3F1/Huming.
Claim 10
Dependent Claim 65 words
A method for evaluating the pharmacokinetic effect, therapeutic value, or medical significance of an agent, on the expression or level of human insulin which comprises: (a) providing said agent a mammal of claim 1 or 2; and (b) examining the effect, value or significance of said agent on the expression or level of said human insulin, by monitoring said expression or level in said mammal.
Claim 11
Dependent Claim 16 words
The method of claim 8, wherein said mammal is a mouse, preferably derived from strain B6C3DF1/Huming.
Claim 12
Independent Claim 76 words
A method for evaluating the pharmacokinetic effect, therapeutic value, or medical significance of an agent on the expression or level of a heterologous protein which comprises: (a) providing said agent to a transgenic mammal, preferably a transgenic mouse, said mammal containing the gene for said heterologous protein; and (b) evaluating the effect, value or significance of said agent on the expression or level of said heterologous protein, by monitoring said expression or level in said mammal.
Claim 13
Independent Claim 76 words
A method for evaluating the pharmacokinetic effect, therapeutic value, or medical significance of an agent on the expression or level of a heterologous protein which comprises: (a) providing said agent to a transgenic mammal, preferably a transgenic mouse, said mammal containing the gene for said heterologous protein; and (b) evaluating the effect, value or significance of said agent on the expression or level of said heterologous protein, by monitoring said expression or level in said mammal.

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