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IgG Fc VARIANTS FOR VETERINARY USE

A variant, amino acid technology, applied in the introduction of foreign genetic material, antibodies, drug combinations, etc. using vectors, can solve the problems of weak CD16 affinity, inability to measure, and weak C1q affinity

Pending Publication Date: 2020-05-19
KINDRED BIOSCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] However, most IgG Fc subtypes of dogs, cats, and horses do not bind Protein A and have weak or no measurable binding affinity for CD16 and weak or no measurable binding affinity for C1q

Method used

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  • IgG Fc VARIANTS FOR VETERINARY USE
  • IgG Fc VARIANTS FOR VETERINARY USE
  • IgG Fc VARIANTS FOR VETERINARY USE

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0474] Variant canine IgG Fc polypeptides with increased protein A binding and / or decreased complement binding and / or decreased CD16 binding

[0475] Purification of antibodies using protein A affinity is a well-established process. However, of the four subtypes of canine IgG, only IgG-B Fc (eg, SEQ ID NO: 2 or SEQ ID NO: 107) has protein A binding affinity. Canine IgG-A Fc (eg, SEQ ID NO: 1), IgG-C Fc (eg, SEQ ID NO: 3 or SEQ ID NO: 108), and IgG-D Fc (eg, SEQ ID NO: 4) have weak or no Measured protein A binding affinity. Variant canine IgG-A Fc, IgG-C Fc and IgG-D Fc polypeptides were designed to alter Protein A binding.

[0476] Furthermore, canine IgG-B Fc and IgG-C Fc have complement activity and bind to C1q, while canine IgG-A Fc and IgG-D Fc have weak or unmeasurable binding affinity for C1q. To potentially reduce C1q binding and / or potentially reduce complement-mediated immune responses, variant canine IgG-B Fc and IgG-C Fc polypeptides were designed.

[0477] In a...

Embodiment 2

[0497] Variant Equine IgG Fc Polypeptides with Increased Protein A Binding and / or Reduced Complement Binding

[0498] Of the seven subtypes of equine IgG, IgG1 Fc (eg, SEQ ID NO: 63), IgG3 Fc (eg, SEQ ID NO: 65), IgG4 Fc (eg, SEQ ID NO: 66), IgG7 Fc (eg, SEQ ID NO: 66), IgG7 Fc (eg, SEQ ID NO: 63) : 69) with protein A binding affinity. Equine IgG2 Fc (eg, SEQ ID NO: 18, SEQ ID NO: 64), IgG5 Fc (eg, SEQ ID NO: 67), and IgG6 Fc (eg, SEQ ID NO: 68) have weak or unmeasurable protein A binding Affinity. Variant equine IgG2 Fc, IgG5 Fc and IgG6 Fc polypeptides were designed to alter protein A binding.

[0499] Furthermore, equine IgG2 Fc, IgG5 Fc, and IgG6 Fc have weak or unmeasurable binding affinity for C1q, while equine IgGl Fc, IgG3 Fc, IgG4 Fc, and IgG7 Fc bind to C1q. Variant equine IgGl Fc, IgG3 Fc, IgG4 Fc and IgG7 Fc polypeptides were designed to potentially reduce C1q binding and / or potentially reduce complement-mediated immune responses.

[0500] Table 6 below summari...

Embodiment 3

[0512] Variant feline IgG Fc polypeptides with reduced complement fixation

[0513]Each of the three subtypes of feline IgG (IgG1a Fc (SEQ ID NO: 80 or SEQ ID NO: 117), IgG1b Fc (SEQ ID NO: 81 or SEQ ID NO: 118) and IgG2 Fc (SEQ ID NO: 118) ID NO: 16)) all have protein A binding affinity. However, only feline IgG2 Fc had weak or unmeasurable binding affinity for C1q, while feline IgG1aFc, IgG1b Fc bound to C1q. To potentially reduce C1q binding and / or potentially reduce complement-mediated immune responses, variant feline IgG1a Fc and IgG1b Fc polypeptides were designed.

[0514] Table 8 below summarizes the protein A and C1q binding properties of feline IgG Fc subtypes. It should be noted that none of the wild-type feline IgG Fc subtypes lacked binding to C1q and binding to protein A.

[0515] Table 8

[0516]

[0517] (–) indicates low or unmeasurable binding activity.

[0518] To potentially reduce the binding of C1q to feline IgG1a Fc and IgG1b Fc, and / or potential...

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Abstract

Provided are various embodiments relating to variant IgG Fc polypeptides of companion animals having increased Protein A binding for ease of purification, decreased C1q binding for reduced complement-mediated immune responses, decreased CD16 binding (e.g., for reduced antibody-dependent cellular cytotoxicity (ADCC) induction, increased stability, and / or the ability to form heterodimeric proteins.In addition, various embodiments relating to antibodies and fusion proteins comprising such variant IgG Fc polypeptides are provided. Also provided are various embodiments relating to contiguous polypeptides comprising one or more variant GLP1 polypeptide(s) having improved serum half-life. Further provided are various embodiments relating to contiguous polypeptides or heterodimeric polypeptides comprising a GLP1 polypeptide and a glucagon polypeptide as a dual GLP1 receptor and glucagon receptor agonist. In various embodiments, such polypeptides may be used to treat, for example, diabetes, obesity, or related indications, in companion animals, such as canines, felines, and equines.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS [0002] This application claims the benefit of priority from US Provisional Application No. 62 / 545,858, filed August 15, 2017, which is incorporated herein by reference in its entirety for any purpose. technical field [0003] The present specification relates to variant IgG Fc polypeptides of companion animals having enhanced characteristics including increased protein A binding (eg, for ease of purification), decreased C1q binding (eg, to reduce complement-mediated immune responses), decreased CD16 Binding (eg, reduced induction of antibody-dependent cellular cytotoxicity (ADCC)), enhanced stability, and / or the ability to form heterodimeric proteins. The variant IgG Fc polypeptides described in this specification may have broad application in the treatment of companion animals. For example, variant IgG Fc polypeptides can be used to design and generate long-acting GLP1 polypeptides for the treatment of companion animals such a...

Claims

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Application Information

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IPC IPC(8): A61K38/17A61K39/395A61K39/40C07K14/31C07K16/28C12N15/82G01N33/68
CPCC07K16/00C07K2317/31C07K2317/52C07K2317/53C07K2317/71C07K2317/94C07K2319/30A61K38/28A61K45/06A61K2300/00A61P3/10A61P3/04A61K2039/505A61K9/0019A61K38/00C07K14/605C07K16/283C07K2317/92
Inventor H·詹L·阮Y·李F·钱S·J·李
Owner KINDRED BIOSCI
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