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。

公开号/公开日
US2016304628 A1 2016-10-20 [US20160304628] / 2016-10-20
申请号/申请日
2014US-15101221 / 2014-12-02
发明人
KRAUSS ISAAC J;HORIYA SATORU;
申请人
BRANDEIS UNIVERSITY;
主分类号
IPC分类号
A61K-039/21C07K-016/10C07K-019/00G01N-033/68
摘要
(US20160304628) 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
代理机构
;
优先权号
2013US-61910710 2013-12-02 2014US-15101221 2014-12-02 2014WO-US68195 2014-12-02
主权利要求
(US20160304628) 1. A glycopolypeptide comprising 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. 2-4. (canceled) 5. The glycopolypeptide according to claim 1, wherein the glycopolypeptide comprises about 10 to about 80 amino acids. 6. (canceled) 7. The glycopolypeptide according to claim 1, wherein the glycopolypeptide comprises from 2 to 5 of said modified amino acid residues. 8-12. (canceled) 13. The glycopolypeptide according to claim 1, wherein the modified amino acid residues comprise a sidechain containing a branched or unbranched oligosaccharide that comprises at least about 3 saccharide moieties. 14-16. (canceled) 17. The glycopolypeptide according to claim 1, wherein modified amino acid comprises a linker molecule between the polypeptide chain and the monosaccharide or 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(.dbd.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; or a disaccharide diradical;   R3 is optional and can be  -- O -- ,  -- S -- , or  -- NR4 -- ; and   R4 iS H or a C1 to C10 alkyl. 18. (canceled) 19. 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. 20. The glycopolypeptide according to claim 1, wherein the carbohydrate-binding monoclonal antibody is neutralizing against a pathogen. 21-22. (canceled) 23. The glycopolypeptide according to claim 1, wherein the carbohydrate-binding monoclonal antibody is cytotoxic against a cancer cell. 24-25. (canceled) 26. The glycopolypeptide according to claim 20, wherein the carbohydrate-binding, neutralizing monoclonal antibody is 2G12 and the glycopolypeptide comprises the sequence XXSIPXYTY (SEQ ID NO: 2) where X is optional and can be any amino acid and X is the modified amino acid residue to which the oligosaccharide is linked. 27. The glycopolypeptide according to claim 26, wherein said glycopolypeptide comprises the sequence:    SequenceSEQ ID NO:XDTLHLKQIGGXPNCITQQDVRXTSIPYTYTWP 3XLLKXVDQSRLXPVPGIGVTLHXRSIPYSYLPI 4XRSTLNSLEYRXQYATEDPRIRXASIPYTYWWP 5ATKTNCKREKTXDNHVTIXRSIPWYTYRWLPN 6XATKTNFKREKTXDNHVTIXRSIPWYTYRWLPN 7XATRTNCKREKTXDNHVTIXRSIPWYTYRWLPN 8XATKTSCKREKTXDNHVTIXRSIPWYTYRWLPN 9XVLPTIISTNVNPFRXLSIPTYTYLXPITWGEI10XTSIPYTYLNRSLWTNYRVNSWSXSKNVNVXPL11XERPSLXCGLSXLTSGGTQSSVXRSIPFYTYWW12XATKTN KREKTXDNHVTIXRSIPWYTYRWLPN53XATKTN KREKTXDNHVTIXRSIPWYTYRWLPN54XRSIPWYTYRWLPN55XDTLHLKQIGGXPN ITQQDVRXTSIPYTYTWP62 28. The glycopolypeptide according to claim 20, wherein the carbohydrate-binding, neutralizing monoclonal antibody is 2G12 and the glycopolypeptide comprises the sequence:    SequenceSEQ ID NO:XHPYNTSRTSAXXAALKXQVTDXYALALFHRIL13XSPHLPVLLCKXVLNDGRRIVQXSCELPXVRRS14XLXFIRIYPTRXQYVYHAPLLTXVRXSPTGPLI15XCYVTVIPAXNXPEARLGIVCHXPGIRRGKALY16XSPHLPVLL KXVLNDGRRIVQXS ELPXVRRS52XXAALKXQVTDXYALALFHRIL56wherein X is the modified amino residue to which the oligosaccharide is linked. 29. A glycopolypeptide comprising from three to five modified amino acid residues having a sidechain comprising a branched oligosaccharide containing 9 mannose moieties, wherein the glycopolypeptide binds specifically to HIV neutralizing monoclonal antibody 2G12 with an affinity that is substantially the same as or lower than the affinity of the 2G12 antibody to gp120. 30-33. (canceled) 34. An immunogenic conjugate comprising a glycopolypeptide according to claim 1 covalently or non-covalently bound to an immunogenic carrier molecule. 35. The immunogenic conjugate according to claim 34, 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. 36. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a glycopolypeptide according to claim 1. 37. The pharmaceutical composition according to claim 36, wherein the glycopolypeptide is present in the form of an immunogenic conjugate comprising the glycopolvpeptide covalently or non-covalently bound to an immunogenic carrier molecule. 38. (canceled) 39. The pharmaceutical composition according to claim 36 further comprising an adjuvant. 40. The pharmaceutical composition according to claim 39, 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 41-43. (canceled) 44. A method of inducing an immune response in an individual comprising: administering to an individual a glycopolypeptide according to claim 1, wherein said administering is effective to induce an immune response against the glycopolypeptide. 45-96. (canceled)
法律状态
(US20160304628) LEGAL DETAILS FOR US2016304628  Actual or expected expiration date=2034-12-02    Legal state=ALIVE    Status=PENDING     Event publication date=2014-12-02  Event code=US/APP  Event indicator=Pos  Event type=Examination events  Application details  Application country=US US15101221  Application date=2014-12-02  Standardized application number=2014US-15101221     Event publication date=2016-08-26  Event code=US/AS  Event type=Change of name or address  Event type=Reassignment  Assignment OWNER: BRANDEIS UNIVERSITY, MASSACHUSETTS ASSIGNMENT OF ASSIGNORS INTEREST ASSIGNORS:KRAUSS, ISAAC J. HORIYA, SATORU SIGNING DATES FROM 20160818 TO 20160822 REEL/FRAME:039845/0376     Event publication date=2016-10-20  Event code=US/A1  Event type=Examination events  Application published  Publication country=US  Publication number=US2016304628  Publication stage Code=A1  Publication date=2016-10-20  Standardized publication number=US20160304628
专利类型码
A1
国别省市代码
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