US2014335075A1PendingUtilityA1

Immunoglobulin constant region fc receptor binding agents

65
Assignee: GLIKNIK INCPriority: Jun 1, 2007Filed: Dec 17, 2013Published: Nov 13, 2014
Est. expiryJun 1, 2027(~0.9 yrs left)· nominal 20-yr term from priority
Inventors:Scott E. StromeDan H. SchulzeDavid S. Block
A61P 43/00A61P 7/04A61P 37/00A61P 7/06A61P 37/06A61P 3/10A61P 37/02A61P 31/22A61P 31/12A61P 33/06A61P 31/04A61P 25/28A61P 35/00A61P 29/00A61P 25/00A61P 1/00A61P 1/04A61P 21/00A61P 19/02A61P 21/04A61P 19/08C07K 2317/524C07K 2319/30C07K 2317/53C07K 16/065C07K 2319/00C07K 2317/55C07K 16/32C07K 2317/52C07K 2317/71A61K 2039/505C07K 16/18C07K 2317/50C07K 16/2863C07K 2317/72A61K 2039/54C07K 2317/35A61K 2039/57G01N 2500/10C07K 16/28C07K 16/00C07K 2317/41C07K 2317/528G01N 33/5047C07K 16/283C07K 2317/73C07K 2318/00C07K 2317/526C07K 2317/92C07K 16/06A61K 39/395G01N 33/53A61K 39/39533Y02A50/30
65
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Claims

Abstract

IVIG replacement compounds are derived from recombinant and/or biochemical creation of immunologically active biomimetic(s). These replacement compounds are then screened in vitro to assess each replacements compound's efficiency at modulating immune function. Particular replacement compounds are selected for further in vivo validation and dosage/administration optimization. Finally, the replacement compounds are used to treat a wide range of diseases, including inflammatory and autoimmune diseases.

Claims

exact text as granted — not AI-modified
1 - 170 . (canceled) 
     
     
         171 . A polypeptide comprising:
 at least a first Fc fragment of IgG and a second Fc fragment of IgG, the first and the second Fc fragments of IgG being attached end-to-end;   at least one of the first and the second Fc fragments of IgG comprising at least one C H 3 domain;   at least one hinge region wherein one said hinge region is positioned at the N-terminus of the polypeptide;   wherein the polypeptide does not comprise a variable region.   
     
     
         172 . The polypeptide of  claim 171 , wherein at least one of the first and the second Fc fragments of IgG further comprises at least one C H 2 domain. 
     
     
         173 . The polypeptide of  claim 171 , wherein the first Fc fragment of IgG further comprises in addition to the hinge region, one C H 2 domain, and the C H 3 domain. 
     
     
         174 . The polypeptide of  claim 171 , wherein a second hinge region is positioned at the C-terminus of the polypeptide. 
     
     
         175 . The polypeptide of  claim 171 , wherein:
 at least one of the first and the second Fc fragments of IgG comprises a second C H 3 domain; and   at least one of the first and the second Fc fragments of IgG comprises a second hinge region.   
     
     
         176 . The polypeptide of  claim 175 , wherein at least one of the first and the second Fc fragments of IgG further comprises at least one C H 2 domain. 
     
     
         177 . The polypeptide of  claim 171 , wherein the at least one first and second Fc fragments of IgG form a chain and said polypeptide comprises two said chains in dimeric form. 
     
     
         178 . The polypeptide of  claim 171 , wherein the at least one first and second Fc fragments of IgG form a chain and said polypeptide comprises multiple said chains in multimeric form. 
     
     
         179 . The polypeptide of  claim 171 , wherein both the first and the second Fc fragments of IgG are selected from a group consisting of an Fc fragment of murine IgG, an Fc fragment of rabbit IgG, and an Fc fragment of human IgG. 
     
     
         180 . The polypeptide of  claim 179 , wherein the Fc fragment of human IgG is selected from a group consisting of an Fc fragment of human IgG1, an Fc fragment of human IgG2, an Fc fragment of human IgG3 and an Fc fragment of human IgG4. 
     
     
         181 . A polypeptide comprising:
 at least a first Fc fragment of IgG and a second Fc fragment of IgG, the first and the second Fc fragments of IgG being attached end-to-end;   at least one of the first and the second Fc fragments of IgG comprising at least one C H 2 domain;   at least one hinge region wherein one said hinge region is positioned on the first Fc fragment at the N-terminus of the polypeptide;   wherein the polypeptide does not comprise a variable region.   
     
     
         182 . The polypeptide of  claim 181 , wherein at least one of the first and the second Fc fragments of IgG further comprises at least one C H 3 domain. 
     
     
         183 . The polypeptide of  claim 181 , wherein the first Fc fragment of IgG further comprises in addition to the hinge region, one C H 2 domain, and the C H 3 domain. 
     
     
         184 . The polypeptide of  claim 181 , wherein a second hinge region is positioned at the C-terminus of the polypeptide. 
     
     
         185 . The polypeptide of  claim 181 , wherein:
 at least one of the first and the second Fc fragments of IgG comprises at least a second C H 2 domain; and   at least one of the first and the second Fc fragments of IgG comprises at least a second hinge region.   
     
     
         186 . The polypeptide of  claim 185 , wherein at least one of the first and the second Fc fragments of IgG further comprises at least one C H 3 domain. 
     
     
         187 . The polypeptide of  claim 181 , wherein the at least one first and second Fc fragments of IgG form a chain and said polypeptide comprises two said chains in dimeric form. 
     
     
         188 . The polypeptide of  claim 181 , wherein the at least one first and second Fc fragments of IgG form a chain and said polypeptide comprises multiple said chains in multimeric form. 
     
     
         189 . The polypeptide of  claim 181 , wherein both the first and the second Fc fragments of IgG are selected from a group consisting of an Fc fragment of murine IgG, an Fc fragment of rabbit IgG, and an Fc fragment of human IgG. 
     
     
         190 . The polypeptide of  claim 189 , wherein the Fc fragment of human IgG is selected from a group consisting of an Fc fragment of human IgG1, an Fc fragment of human IgG2, an Fc fragment of human IgG3 and an Fc fragment of human IgG4. 
     
     
         191 . A polypeptide comprising:
 at least a first Fc fragment of IgG and a second Fc fragment of IgG, the first and the second Fc fragments of IgG being attached end-to-end;   at least one of the first and the second Fc fragments of IgG comprising at least a portion of an amino acid sequence of the Fc region of IgG;   at least one hinge region wherein one said hinge region is positioned at the N-terminus of the polypeptide;   wherein the polypeptide does not comprise a variable region.   
     
     
         192 . The polypeptide of  claim 191 , wherein the first Fc fragment of IgG further comprises in addition to the hinge region, one C H 2 domain, and one C H 3 domain. 
     
     
         193 . The polypeptide of  claim 191 , wherein a second hinge region is positioned at the C-terminus of the polypeptide. 
     
     
         194 . The polypeptide of  claim 191 , wherein the at least one first and second Fc fragments of IgG form a chain and said polypeptide comprises two said chains in dimeric form. 
     
     
         195 . The polypeptide of  claim 191 , wherein the at least one first and second Fc fragments of IgG form a chain and said polypeptide comprises multiple said chains in multimeric form. 
     
     
         196 . The polypeptide of  claim 191 , wherein both the first and the second Fc fragments of IgG are selected from a group consisting of an Fc fragment of murine IgG, an Fc fragment of rabbit IgG, and an Fc fragment of human IgG. 
     
     
         197 . The polypeptide of  claim 196 , wherein the Fc fragment of human IgG is selected from a group consisting of an Fc fragment of human IgG1, an Fc fragment of human IgG2, an Fc fragment of human IgG3 and an Fc fragment of human IgG4. 
     
     
         198 . The polypeptide of  claim 177 , wherein the polypeptide comprising two chains in dimeric form is configured to bind and cross-link at least two Fc-gamma receptors on a stimulated cell. 
     
     
         199 . The polypeptide of  claim 187 , wherein the polypeptide comprising two chains in dimeric form is configured to bind and cross-link at least two Fc-gamma receptors on a stimulated cell. 
     
     
         200 . The polypeptide of  claim 194 , wherein the polypeptide comprising two chains in dimeric form is configured to bind and cross-link at least two Fc-gamma receptors on a stimulated cell. 
     
     
         201 . The polypeptide of  claim 171 , wherein one of a second hinge region, a C H 2 domain, and the C H 3 domain is positioned at the C-terminus of the polypeptide. 
     
     
         202 . The polypeptide of  claim 181 , wherein one of a second hinge region, the C H 2 domain, and a C H 3 domain is positioned at the C-terminus of the polypeptide. 
     
     
         203 . The polypeptide of  claim 191 , wherein one of a second hinge region, a C H 2 domain, and a C H 3 domain is positioned at the C-terminus of the polypeptide. 
     
     
         204 . The polypeptide of  claim 171 , wherein the second Fc fragment of IgG comprises one C H 2 domain, the C H 3 domain, and an additional hinge region. 
     
     
         205 . The polypeptide of  claim 181 , wherein the second Fc fragment of IgG comprises the C H 2 domain, one C H 3 domain, and an additional hinge region. 
     
     
         206 . The polypeptide of  claim 191 , wherein the second Fc fragment of IgG comprises one C H 2 domain, one C H 3 domain, and an additional hinge region. 
     
     
         207 . The polypeptide of  claim 171 , wherein at least one of the first and the second Fc fragments of IgG comprises each of one C H 2 domain, a second C H 3 domain, and a second hinge region. 
     
     
         208 . The polypeptide of  claim 181 , wherein at least one of the first and the second Fc fragments of IgG comprises each of at least a second C H 2 domain, one C H 3 domain, and a second hinge region. 
     
     
         209 . A polypeptide comprising:
 at least a first Fc fragment of IgG and a second Fc fragment of IgG, the first and the second Fc fragments of IgG being attached end-to-end;   at least one of the first and the second Fc fragments of IgG comprising at least one C H 3 domain;   at least one hinge region wherein the at least one hinge region is positioned at the N-terminus of the first Fc fragment of IgG and wherein the N-terminus of the first Fc fragment of IgG is positioned at the N-terminus of the polypeptide;   wherein the polypeptide does not comprise a variable region.   
     
     
         210 . A method of reducing macrophage-mediated inflammation in a patient, the method comprising:
 administering to the patient, a therapeutically effective amount of a polypeptide, the polypeptide comprising:
 at least a first Fc fragment of IgG and a second Fc fragment of IgG, the first and the second Fc fragments of IgG being attached end-to-end; 
 at least one of the first and the second Fc fragments of IgG comprising at least one C H 3 domain; 
 at least one hinge region wherein one said hinge region is positioned at the N-terminus of the polypeptide; 
 wherein the polypeptide does not comprise a variable region. 
   
     
     
         211 . The method of  claim 210 , wherein the patient has a condition which includes macrophage-mediated inflammation as one symptom. 
     
     
         212 . The method of  claim 210 , wherein at least one of the first and the second Fc fragments of IgG further comprises at least one C H 2 domain. 
     
     
         213 . The method of  claim 210 , wherein the first Fc fragment of IgG further comprises in addition to the hinge region, one C H 2 domain, and the C H 3 domain. 
     
     
         214 . The method of  claim 210 , wherein a second hinge region is positioned at the C-terminus of the polypeptide. 
     
     
         215 . The method of  claim 210 , wherein:
 at least one of the first and the second Fc fragments of IgG comprises a second C H 3 domain; and   at least one of the first and the second Fc fragments of IgG comprises a second hinge region.   
     
     
         216 . The method of  claim 215 , wherein at least one of the first and the second Fc fragments of IgG further comprises at least one C H 2 domain. 
     
     
         217 . The method of  claim 210 , wherein the at least one first and second Fc fragments of IgG form a chain and said polypeptide comprises two said chains in dimeric form. 
     
     
         218 . The method of  claim 210 , wherein the at least one first and second Fc fragments of IgG form a chain and said polypeptide comprises multiple said chains in multimeric form. 
     
     
         219 . The method of  claim 210 , wherein both the first and the second Fc fragments of IgG are selected from a group consisting of an Fc fragment of murine IgG, an Fc fragment of rabbit IgG, and an Fc fragment of human IgG. 
     
     
         220 . The method of  claim 219 , wherein the Fc fragment of human IgG is selected from a group consisting of an Fc fragment of human IgG1, an Fc fragment of human IgG2, an Fc fragment of human IgG3 and an Fc fragment of human IgG4. 
     
     
         221 . A method of reducing macrophage-mediated inflammation in a patient comprising:
 administering to the patient, a therapeutically effective amount of a polypeptide, the polypeptide comprising:
 at least a first Fc fragment of IgG and a second Fc fragment of IgG, the first and the second Fc fragments of IgG being attached end-to-end; 
 at least one of the first and the second Fc fragments of IgG comprising at least one C H 2 domain; 
 at least one hinge region wherein one said hinge region is positioned on the first Fc fragment at the N-terminus of the polypeptide; 
 wherein the polypeptide does not comprise a variable region. 
   
     
     
         222 . The method of  claim 221 , wherein the patient has a condition which includes macrophage-mediated inflammation as one symptom. 
     
     
         223 . The method of  claim 221 , wherein at least one of the first and the second Fc fragments of IgG further comprises at least one C H 3 domain. 
     
     
         224 . The method of  claim 221 , wherein the first Fc fragment of IgG further comprises in addition to the hinge region, one C H 2 domain, and the C H 3 domain. 
     
     
         225 . The method of  claim 221 , wherein a second hinge region is positioned at the C-terminus of the polypeptide. 
     
     
         226 . The method of  claim 221 , wherein:
 at least one of the first and the second Fc fragments of IgG comprises at least a second C H 2 domain; and   at least one of the first and the second Fc fragments of IgG comprises at least a second hinge region.   
     
     
         227 . The method of  claim 226 , wherein at least one of the first and the second Fc fragments of IgG further comprises at least one C H 3 domain. 
     
     
         228 . The method of  claim 221 , wherein the at least one first and second Fc fragments of IgG form a chain and said polypeptide comprises two said chains in dimeric form. 
     
     
         229 . The method of  claim 221 , wherein the at least one first and second Fc fragments of IgG form a chain and said polypeptide comprises multiple said chains in mulimeric form. 
     
     
         230 . The method of  claim 221 , wherein both the first and the second Fc fragments of IgG are selected from a group consisting of an Fc fragment of murine IgG, an Fc fragment of rabbit IgG, and an Fc fragment of human IgG. 
     
     
         231 . The method of  claim 230 , wherein the Fc fragment of human IgG is selected from a group consisting of an Fc fragment of human IgG1, an Fc fragment of human IgG2, an Fc fragment of human IgG3 and an Fc fragment of human IgG4. 
     
     
         232 . A method of reducing macrophage-mediated inflammation in a patient comprising:
 administering to the patient, a therapeutically effective amount of a polypeptide, the polypeptide comprising:
 at least a first Fc fragment of IgG and a second Fc fragment of IgG, the first and the second Fc fragments of IgG being attached end-to-end; 
 at least one of the first and the second Fc fragments of IgG comprising at least a portion of an amino acid sequence of the Fc region of IgG; 
 at least one hinge region wherein one said hinge region is positioned at the N-terminus of the polypeptide; 
 wherein the polypeptide does not comprise a variable region. 
   
     
     
         233 . The method of  claim 232 , wherein the patient has a condition which includes macrophage-mediated inflammation as one symptom. 
     
     
         234 . The method of  claim 232 , wherein the first Fc fragment of IgG further comprises in addition to the hinge region, one C H 2 domain, and one C H 3 domain. 
     
     
         235 . The method of  claim 232 , wherein a second hinge region is positioned at the C-terminus of the polypeptide. 
     
     
         236 . The method of  claim 232 , wherein the at least one first and second Fc fragments of IgG form a chain and said polypeptide comprises two said chains in dimeric form. 
     
     
         237 . The method of  claim 232 , wherein the at least one first and second Fc fragments of IgG form a chain and said polypeptide comprises multiple said chains in multimeric form. 
     
     
         238 . The method of  claim 232 , wherein both the first and the second Fc fragments of IgG are selected from a group consisting of an Fc fragment of murine IgG, an Fc fragment of rabbit IgG, and an Fc fragment of human IgG. 
     
     
         239 . The method of  claim 238 , wherein the Fc fragment of human IgG is selected from a group consisting of an Fc fragment of human IgG1, an Fc fragment of human IgG2, an Fc fragment of human IgG3 and an Fc fragment of human IgG4. 
     
     
         240 . The method of  claim 210 , wherein one of a second hinge region, a C H 2 domain, and the C H 3 domain is positioned at the C-terminus of the polypeptide. 
     
     
         241 . The method of  claim 221 , wherein one of a second hinge region, the C H 2 domain, and a C H 3 domain is positioned at the C-terminus of the polypeptide. 
     
     
         242 . The method of  claim 232 , wherein one of a second hinge region, a C H 2 domain, and a C H 3 domain is positioned at the C-terminus of the polypeptide. 
     
     
         243 . The method of  claim 210 , wherein the second Fc fragment of IgG comprises one C H 2 domain, the C H 3 domain, and an additional hinge region. 
     
     
         244 . The method of  claim 221 , wherein the second Fc fragment of IgG comprises the C H 2 domain, one C H 3 domain, and an additional hinge region. 
     
     
         245 . The method of  claim 232 , wherein the second Fc fragment of IgG comprises one C H 2 domain, one C H 3 domain, and an additional hinge region. 
     
     
         246 . The method of  claim 210 , wherein at least one of the first and the second Fc fragments of IgG comprises each of one C H 2 domain, a second C H 3 domain, and a second hinge region. 
     
     
         247 . The method of  claim 221 , wherein at least one of the first and the second Fc fragments of IgG comprises each of at least a second C H 2 domain, one C H 3 domain, and a second hinge region. 
     
     
         248 . A method of reducing macrophage-mediated inflammation in a patient comprising:
 administering to the patient, a therapeutically effective amount of a polypeptide, the polypeptide comprising:   at least a first Fc fragment of IgG and a second Fc fragment of IgG, the first and the second Fc fragments of IgG being attached end-to-end;   at least one of the first and the second Fc fragments of IgG comprising at least one C H 3 domain;   at least one hinge region wherein the at least one hinge region is positioned at the N-terminus of the first Fc fragment of IgG and wherein the N-terminus of the first Fc fragment of IgG is positioned at the N-terminus of the polypeptide;   wherein the polypeptide does not comprise a variable region.   
     
     
         249 . A polypeptide comprising:
 a first Fc fragment of IgG and a second Fc fragment of IgG, the first and the second Fc fragments of IgG being attached in a series;   the first Fc fragment of IgG comprising a full-length hinge region and a full-length CH3 domain;   the second Fc fragment of IgG comprising a full-length CH3 domain;   wherein the hinge region of the first Fc fragment of IgG is the N-terminus of the first Fc fragment of IgG and wherein the N-terminus of the first Fc fragment of IgG is the N-terminus of the polypeptide; and   wherein the CH3 domain of the second Fc fragment of IgG is the C-terminus of the second fragment of IgG and wherein the C-terminus of the second Fc fragment of IgG is the C-terminus of the polypeptide.   
     
     
         250 . A polypeptide comprising:
 a first Fc fragment of IgG and a second Fc fragment of IgG, the first and the second Fc fragments of IgG being attached in a series;   the first Fc fragment of IgG consisting of a full-length hinge region, a full-length CH3 domain, and a CH2 domain positioned intermediate to the hinge and CH3 domain;   the second Fc fragment of IgG consisting of a CH2 domain and a full-length CH3 domain;   wherein the hinge region of the first Fc fragment of IgG is the N-terminus of the first Fc fragment of IgG and wherein the N-terminus of the first Fc fragment of IgG is the N-terminus of the peptide;   wherein the CH3 domain of the second Fc fragment of IgG is the C-terminus of the second Fc fragment of IgG and wherein the C-terminus of the second Fc fragment of IgG is the C-terminus of the polypeptide.   
     
     
         251 . The polypeptide of  claim 250 , wherein the first Fc fragment of IgG and the second Fc fragment of IgG form a chain and said polypeptide comprises two said chains in dimeric form. 
     
     
         252 . The polypeptide of  claim 250 , wherein the first Fc fragment of IgG and the second Fc fragment of IgG form a chain and said polypeptide comprises multiple said chains in multimeric form. 
     
     
         253 . The polypeptide of  claim 250 , wherein the first Fc fragment of IgG and the second Fc fragment of IgG are each selected from one of a group consisting of an Fc fragment of murine IgG, an Fc fragment of rabbit IgG, and an Fc fragment of human IgG. 
     
     
         254 . The polypeptide of  claim 251 , wherein the polypeptide comprising two chains in dimeric form is configured to bind and cross-link at least two Fc-gamma receptors on a stimulated cell. 
     
     
         255 . A polypeptide comprising:
 a first Fc fragment of IgG and a second Fc fragment of IgG, the first and the second Fc fragments of IgG being attached in a series;   the first Fc fragment of IgG consisting of a full-length hinge region, a full-length CH3 domain, and a full-length CH2 domain positioned intermediate to the hinge region and CH3 domain;   the second Fc fragment of IgG consisting of a full-length hinge region, a full-length CH3 domain, and a full-length CH2 domain positioned intermediate to the hinge region and CH3 domain;   wherein the hinge region of the first Fc fragment of IgG is the N-terminus of the first Fc fragment of IgG and wherein the N-terminus of the first Fc fragment of IgG is the N-terminus of the polypeptide;   wherein the CH3 domain of the second Fc fragment of IgG is the C-terminus of the second Fc fragment of IgG and wherein the C-terminus of the second Fc fragment of IgG is the C-terminus of the polypeptide; wherein the first Fc fragment of IgG and the second Fc fragment of IgG are bound through one hinge region, the one hinge region being the hinge region of the second Fc fragment of IgG;   wherein the first Fc fragment of IgG and the second Fc fragment of IgG form a chain and said polypeptide comprises two said chains in dimeric form configured to bind and cross-link at least two Fc-gamma receptors on a stimulated cell.   
     
     
         256 . The polypeptide of  claim 255 , wherein the first Fc fragment of IgG and the second Fc fragment of IgG are each selected from one of a group consisting of an Fc fragment of murine IgG, an Fc fragment of rabbit IgG, and an Fc fragment of human IgG. 
     
     
         257 . The polypeptide of  claim 255 , wherein the first Fc fragment of IgG and the second Fc fragment of IgG are Fc fragments of human IgG. 
     
     
         258 . The polypeptide of  claim 257 , wherein the Fc fragments of human IgG are selected from a group consisting of Fc fragments of human IgG1, Fc fragments of human IgG2, Fc fragments of human IgG3 and Fc fragments of human IgG4. 
     
     
         259 . A polypeptide comprising:
 a first Fc fragment of IgG and a second Fc fragment of IgG, the first and the second Fc fragments of IgG being attached in a series;   the first Fc fragment of IgG consisting of a full-length hinge region, a full-length CH3 domain, and a full-length CH2 domain positioned intermediate to the hinge region and CH3 domain;   the second Fc fragment of IgG consisting of a full-length hinge region, a full-length CH3 domain, and a full-length CH2 domain positioned intermediate to the hinge region and CH3 domain;   wherein the hinge region of the first Fc fragment of IgG is the N-terminus of the first Fc fragment of IgG and wherein the N-terminus of the first Fc fragment of IgG is the N-terminus of the polypeptide;   wherein the CH3 domain of the second Fc fragment of IgG is the C-terminus of the second Fc fragment of IgG and wherein the C-terminus of the second Fc fragment of IgG is the C-terminus of the polypeptide;   wherein the first Fc fragment of IgG and the second Fc fragment of IgG are bound through one hinge region, the one hinge region being the hinge region of the second Fc fragment of IgG;   wherein the first Fc fragment of IgG and the second Fc fragment of IgG form a chain and said polypeptide comprises multiple said chains in multimeric form configured to bind and cross-link at least two Fc-gamma receptors on a stimulated cell.

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