(US10563193) Multivalent glycopeptides that tightly bind to target proteins 机翻标题: 暂无翻译,请尝试点击翻译按钮。

源语言标题
(US10563193) Multivalent glycopeptides that tightly bind to target proteins
公开号/公开日
US10563193 US20160304628 / 2020-02-18 2016-10-20
申请号/申请日
US15/101,221 / 2014-12-02
发明人
KRAUSS ISAAC JHORIYA SATORU;
申请人
BRANDEIS UNIVERSITY;
主分类号
IPC分类号
A61K-039/00 A61K-039/21 C07K-016/10 C07K-019/00 C12N-015/10 G01N-033/68
摘要
(US10563193) The invention relates to a glycopolypeptide that includes one or more modified amino acid residues having a sidechain comprising a monosaccharide or an oligosaccharide, wherein the glycopolypeptide binds specifically to a carbohydrate-binding monoclonal antibody with an affinity of less than 100 nM. Immunogenic conjugates that include the glycopolypeptide, and pharmaceutical compositions that include the glycopolypeptide or the immunogenic conjugate are also disclosed. Various method of using the glycopolypeptides, immunogenic conjugates, and pharmaceutical compositions are disclosed, including inducing an immune response, inhibiting viral or bacterial infection, treating a cancerous condition, and detecting a neutralizing antibody.
机翻摘要
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地址
代理人
(US10563193) Pepper Hamilton LLP
代理机构
;
优先权号
2013US-61910710 2014US-15101221 2014WO-US68195
主权利要求
(US10563193) What is claimed: 1. A glycopolypeptide comprising 10 to 80 amino acids, said amino acids including one to ten modified amino acid residues having a sidechain comprising a branched oligosaccharide comprising nine mannose moieties, and said amino acids including the amino acid sequence of XxSIPxYTY (SEQ ID NO: 2) wherein each x at positions 2 and 6 is optional and can be any natural amino acid, and X at position 1 is one of said modified amino acid residues, wherein the glycopolypeptide binds specifically to carbohydrate-binding monoclonal antibody 2G12 with a Kd of less than 100 nM and wherein each modified amino acid residue comprises a linker molecule between the polypeptide chain and the branched oligosaccharide, the linker molecule comprising wherein each of R1 and R2 is optionally a direct link or independently selected from the group consisting of a linear or branched C1 to C18 hydrocarbon that is saturated or mono- or poly-unsaturated, optionally interrupted by one or more non-adjacent —O—, —C(═O)—, or —NR4—; a substituted or unsubstituted C3 to C10 cycloalkanediyl, a substituted or unsubstituted aryl diradical; a substituted or unsubstituted heteroaryl diradical; a monosaccharide diradical; and a disaccharide diradical;   R3 is optional and can be —O—, —S—, or —NR4—; and   R4 is H or a C1 to C10 alkyl. 2. The glycopolypeptide according to claim 1, wherein the glycopolypeptide comprises from 15 to 70 amino acids. 3. The glycopolypeptide according to claim 1, wherein the glycopolypeptide comprises from 2 to 5 of said modified amino acid residues. 4. The glycopolypeptide according to claim 1, wherein the glycopolypeptide binds specifically to the carbohydrate-binding monoclonal antibody with an affinity that is substantially the same as or lower than the affinity of the carbohydrate-binding monoclonal antibody to its naturally occurring binding partner. 5. The glycopolypeptide according to claim 1, wherein the carbohydrate-binding monoclonal antibody is neutralizing against a pathogen. 6. The glycopolypeptide according to claim 1, wherein said glycopolypeptide comprises one of the following sequences:  SequenceSEQ ID NO: XDTLHLKQIGGXPNCITQQDVRXTSIPYTYTWP 3 XRSTLNSLEYRXQYATEDPRIRXASIPYTYWWP 5 ATKTNCKREKTXDNHVTIXRSIPWYTYRWLPN 6 XATKTNFKREKTXDNHVTIXRSIPWYTYRWLPN 7 XATRTNCKREKTXDNHVTIXRSIPWYTYRWLPN 8 XATKTSCKREKTXDNHVTIXRSIPWYTYRWLPN 9 XVLPTIISTNVNPFRXLSIPTYTYLXPITWGEI10 XTSIPYTYLNRSLWTNYRVNSWSXSKNVNVXPL11 XERPSLXCGLSXLTSGGTQSSVXRSIPFYTYWW12 XATKTNSKREKTXDNHVTIXRSIPWYTYRWLPN53 XATKTNSKREKTXDNHVTIXRSIPWYTYRWLPN54 XRSIPWYTYRWLPN55 XDTLHLKQIGGXPNSITQQDVRXTSIPYTYTWP62  wherein each X is one of said modified amino acid residues to which the branched oligosaccharide is linked. 7. A glycopolypeptide comprising 10 to 80 amino acids, said amino acids including one to ten modified amino acid residues having a sidechain comprising a branched oligosaccharide comprising nine mannose moieties, wherein the glycopeptide binds specifically to carbohydrate-binding, neutralizing monoclonal antibody 2G12 with a Kd of less than 100 nM and wherein the glycopolypeptide comprises the amino acid sequence:  SequenceSEQ ID NO:  XLLKXVDQSRLXPVPGIGVTLHXRSIPYSYLPI4 XHPYNTSRTSAXXAALKXQVTDXYALALFHRIL13XSPHLPVLLCKXVLNDGRRIVQXSCELPXVRRS14 XLXFIRIYPTRXQYVYHAPLLTXVRXSPTGPLI15 XCYVTVIPAXNXPEARLGIVCHXPGIRRGKALY16 XSPHLPVLLSKXVLNDGRRIVQXSSELPXVRRS52 XXAALKXQVTDXYALALFHRIL56  wherein each X is one of said modified amino residues to which the branched oligosaccharide is linked. 8. An immunogenic conjugate comprising a glycopolypeptide according to claim 1 covalently or non-covalently bound to an immunogenic carrier molecule. 9. The immunogenic conjugate according to claim 8, wherein the immunogenic carrier molecule is selected from the group consisting of bovine serum albumin, chicken egg ovalbumin, keyhole limpet hemocyanin, tetanus toxoid, diphtheria toxoid, thyroglobulin, a pneumococcal capsular polysaccharide, CRM 197, and a meningococcal outer membrane protein. 10. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a glycopolypeptide according to claim 1. 11. The pharmaceutical composition according to claim 10, wherein the glycopolypeptide is present in the form of an immunogenic conjugate comprising the glycopolypeptide covalently or non-covalently bound to an immunogenic carrier molecule. 12. The pharmaceutical composition according to claim 10 further comprising an adjuvant. 13. The pharmaceutical composition according to claim 12, wherein the adjuvant comprises aluminum hydroxide, aluminum phosphate, aluminum potassium sulfate, beryllium sulfate, silica, kaolin, carbon, water-in-oil emulsions, oil-in-water emulsions, muramyl dipeptide, bacterial endotoxin, lipid, Quil A, non-infective Bordetella pertussis, QS-21, monophosphoryl lipid A, an alpha-galactosylceramide derivative, or PamCys-type lipids. 14. A glycopolypeptide comprising one or more modified amino acid residues having a sidechain linked to a branched oligosaccharide comprising nine mannose moieties, wherein the glycopolypeptide binds specifically to monoclonal antibody 2G12 with a Kd of less than 100 nM and wherein said glycopolypeptide comprises one of the following sequences:  Sequence  SEQ ID NO:  XDTLHLKQIGGXPNCITQQDVRXTSIPYTYTWP3XLLKXVDQSRLXPVPGIGVTLHXRSIPYSYLPI4XRSTLNSLEYRXQYATEDPRIRXASIPYTYWWP5ATKTNCKREKTXDNHVTIXRSIPWYTYRWLPN6XATKTNFKREKTXDNHVTIXRSIPWYTYRWLPN7XATRTNCKREKTXDNHVTIXRSIPWYTYRWLPN8XATKTSCKREKTXDNHVTIXRSIPWYTYRWLPN9XVLPTIISTNVNPFRXLSIPTYTYLXPITWGEI10XTSIPYTYLNRSLWTNYRVNSWSXSKNVNVXPL11XERPSLXCGLSXLTSGGTQSSVXRSIPFYTYWW12XHPYNTSRTSAXXAALKXQVTDXYALALFHRIL13XSPHLPVLLCKXVLNDGRRIVQXSCELPXVRRS14XLXFIRIYPTRXQYVYHAPLLTXVRXSPTGPLI15XCYVTVIPAXNXPEARLGIVCHXPGIRRGKALY16XSPHLPVLLSKXVLNDGRRIVQXSSELPXVRRS52XXAALKXQVTDXYALALFHRIL56XDTLHLKQIGGXPNSITQQDVRXTSIPYTYTWP62  wherein each X is one of said modified amino acid residues to which the branched oligosaccharide is linked. 15. An immunogenic conjugate comprising a glycopolypeptide according to claim 14 covalently or non-covalently bound to an immunogenic carrier molecule. 16. The immunogenic conjugate according to claim 15, wherein the immunogenic carrier molecule is selected from the group consisting of bovine serum albumin, chicken egg ovalbumin, keyhole limpet hemocyanin, tetanus toxoid, diphtheria toxoid, thyroglobulin, a pneumococcal capsular polysaccharide, CRM 197, and a meningococcal outer membrane protein. 17. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a glycopolypeptide according to claim 7. 18. The pharmaceutical composition according to claim 17, wherein the glycopolypeptide is present in the form of an immunogenic conjugate comprising the glycopolypeptide covalently or non-covalently bound to an immunogenic carrier molecule. 19. The pharmaceutical composition according to claim 17 further comprising an adjuvant. 20. The pharmaceutical composition according to claim 19, wherein the adjuvant comprises aluminum hydroxide, aluminum phosphate, aluminum potassium sulfate, beryllium sulfate, silica, kaolin, carbon, water-in-oil emulsions, oil-in-water emulsions, muramyl dipeptide, bacterial endotoxin, lipid, Quil A, non-infective Bordetella pertussis, QS-21, monophosphoryl lipid A, an alpha-galactosylceramide derivative, or PamCys-type lipids.
法律状态
GRANTED
专利类型码
B2 A1
国别省市代码
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