Back to results
US 2014/0154282 A1Published application
Conjugates utilizing platform technology for stimulating immune response
OwnerRobert S. Hodges, Kathryn V. Holmes +4inventors
InventorsRobert S. Hodges, Kathryn V. Holmes, Zhe Yan, Wendy Jeanne Hartsock, Zhaohui Qian, Brooke Elizabeth Bishop Hirsch
Life of this patent
Estimating the term…
Abstract
Templated conjugates created from naturally-occurring protein sequences found in pathogens, such as viruses, are disclosed. The sequences are “templated” into a consensus coiled-coil sequence in a platform in order to form a two-stranded antigen suitable for immunization of a subject.
Claims18
A conjugate, comprising:
- two templated alpha helical polypeptides of approximately equal length, wherein each polypeptide comprises at least two heptad repeats, and wherein the polypeptides are derived from at least one virus;
- a covalent linkage between the two polypeptides;
- and
- a carrier protein covalently linked to one of the polypeptides;
- wherein the first polypeptide comprises the form:
- [I-b1i-c1i-L-e1i-f1i-g1i]n,
- where [I-b1i-c1i-L-e1i-f1i-g1i] is a pattern that repeats n times in the sequence of the first polypeptide, giving rise to at least two discrete seven-amino-acid segments,
- where I in each segment is isoleucine,
- L in each segment is leucine,
- n is an integer of at least 2;
- i is an integer from 1 to n, wherein the value of i is determined by the position of the segment in which it appears, such that the N-terminal segment which appears first in the sequence is assigned a value of i=1, i is incremented by one for each additional segment, and the C-terminal segment is assigned a value of i=n;
- where each b, c, e, f, and g in each of the n segments is selected independently of each b, c, e, f, and g amino acid in all other segments of the first polypeptide, and of all segments of the second polypeptide;
- the b, c, e, f, and g amino acids are selected from an epitope;
- the second polypeptide comprises the form:
- [I-b2i-c2i-L-e2i-f2i-g2i]n,
- where [I-b2i-c2i-L-e2i-f2i-g2i] is a pattern that repeats n times in the sequence of the second polypeptide, giving rise to at least two discrete seven-amino-acid segments,
- where I in each segment is isoleucine,
- L in each segment is leucine,
- n is an integer of at least 2 and is the same as n for the first polypeptide;
- i is an integer from 1 to n, wherein the value of i is determined by the position of the segment in which it appears, such that the N-terminal segment which appears first in the sequence is assigned a value of i=1, i is incremented by one for each additional segment, and the C-terminal segment is assigned a value of i=n;
- where each b, c, e, f, and g in each of the n segments is selected independently of each b, c, e, f, and g amino acid in all other segments of the second polypeptide, and of all segments of the first polypeptide;
- the b, c, e, f, and g amino acids are selected from an epitope which is different from the epitope of the first polypeptide;
- wherein the conjugate has the form:
- [Carrier Moiety]-[Linker A]-[Linker B1]-[Templated Epitope 1]-[Epitope 1 Modifier]
- [Modifier B2]-[Templated Epitope 2]-[Epitope 2 Modifier]
- where Carrier Moiety, Linker A, Linker B 1, Modifier B2, Epitope 1 Modifier, and Epitope 2 Modifier are optionally present;
- and
- optionally comprising an additional covalent Linker C between Templated Epitope 1 and Templated Epitope 2;
- optionally comprising an additional covalent Linker D between Epitope 1 Modifier and Epitope 2 Modifier, or
- optionally comprising an additional covalent Linker C between Templated Epitope 1 and Templated Epitope 2 and an additional covalent Linker D between Epitope 1 Modifier and Epitope 2 Modifier, wherein the Epitope 1 Modifier and the Epitope 2 Modifier are present and are selected from hydrophilic, polar, and charged amino acids, wherein the [Linker A] moiety is present, wherein the [Linker B1] moiety is present;
- with the proviso that either both Epitope 1 Modifier and Epitope 2 Modifier are present, or Linker C is present, or Linker D is present.
28 more elements
Dependencies are inferred from the claim text.