US2022017586A1PendingUtilityA1
Exposed collagen-targeted fusion cytokine for immune modulation in invasive cancers and lesions of infections
Assignee: COUNTERPOINT BIOMEDICA LLCPriority: Jan 25, 2017Filed: Jan 19, 2021Published: Jan 20, 2022
Est. expiryJan 25, 2037(~10.5 yrs left)· nominal 20-yr term from priority
A61K 38/193A61K 38/37C07K 14/78C07K 14/56C07K 14/52C07K 2319/21C07K 14/535C07K 2319/01C07K 2319/02C12N 2800/22C07K 14/55C07K 2319/33C12N 15/85A61P 35/00C07K 14/755
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Claims
Abstract
Provided herein are new compositions and methods to target pharmaceutical agents to pathological areas by utilizing fusion polypeptides. These fusion polypeptides contain two or more domains: (i) aptamer sequences that bind to exposed collagenous (XC-) proteins present in pathological areas, including cancerous and viral lesions, (ii) immunomodulators, such as cytokines, and optionally (iii) at least one linker joining the two domains or at the terminus of the polypeptide. In some cases, the linker is a rigid linker, e.g., a rigid helical linker. Also provided herein are methods of treating cancer and/or infectious diseases using the new fusion polypeptides.
Claims
exact text as granted — not AI-modified1 - 84 . (canceled)
85 . A method of treating an infection in a subject comprising administering to a subject in need of such treatment a fusion polypeptide comprising an amino acid sequence selected from the group consisting of:
APARSPSPSTQPWEHVNAIQEARRLLNLSRDTAAEMNETVEVISEMFDLQEPTCLQTRLE LYKQGLRGSLTKLKGPLTMMASHYKQHCPPTPETSCATQIITFESFKENLKDFLLVIPFDC WEPVQEGAEAAAKEAAAKAGARRGVRVAWREPGRMELNMPHGQE (SEQ ID NO: 17); APARSPSPSTQPWEHVNAIQEARRLLNLSRDTAAEMNETVEVISEMFDLQEPTCLQTRLE LYKQGLRGSLTKLKGPLTMMASHYKQHCPPTPETSCATQIITFESFKENLKDFLLVIPFDC WEPVQEGSAGSAAGSGARRGVRVAWREPGRMELNMPHGQE (SEQ ID NO: 18); METDTLLLWVLLLWVPGSTGREEFEEEFEHREEFEFEENLYFQGAPARSPSPSTQPWEHVNAIQE ARRLLNLSRDTAAEMNETVEVISEMFDLQEPTCLQTRLELYKQGLRGSLTKLKGPLTMM ASHYKQHCPPTPETSCATQIITFESFKENLKDFLLVIPFDCWEPVQEGAEAAAKEAAAKA GARRGVRVAWREPGRMELNMPHGQE (SEQ ID NO: 19); 1VIETDTLLLWVLLLWVPGSTGREEFEEEFEHREEFEFEENLYFQGAPARSPSPSTQPWEHVNAIQE ARRLLNLSRDTAAEMNETVEVISEMFDLQEPTCLQTRLELYKQGLRGSLTKLKGPLTMM ASHYKQHCPPTPETSCATQIITFESFKENLKDFLLVIPFDCWEPVQEGSAGSAAGSGARR GVRVAWREPGRMELNMPHGQE (SEQ ID NO: 40); METDTLLLWVLLLWVPGSTGREEFEEEFEHREEFEHENLYFQGARRGVHVGWREPGRMELN MPHGGAEAAAKEAAAKAGAPARSPSPSTQPWEHVNAIQEARRLLNLSRDTAAEMNET VEVISEMFDLQEPTCLQTRLELYKQGLRGSLTKLKGPLTMMASHYKQHCPPTPETSCAT QIITFESFKENLKDFLLVIPFDCWEPVQE (SEQ ID NO: 36); and RRGVHVGWREPGRMELNMPHGGAEAAAKEAAAKAGAPARSPSPSTQPWEHVNAIQEA RRLLNLSRDTAAEMNETVEVISEMFDLQEPTCLQTRLELYKQGLRGSLTKLKGPLTMMA SHYKQHCPPTPETSCATQIITFESFKENLKDFLLVIPFDCWEPVQE (SEQ ID NO: 39) in an amount sufficient to treat the infection.
86 . The method of claim 85 , wherein the fusion polypeptide further comprises a purification tag or an export signal peptide.
87 . The method of claim 85 , wherein fusion polypeptide comprises the amino acid sequence:
(SEQ ID NO: 17)
APARSPSPSTQPWEHVNAIQEARRLLNLSRDTAAEMNETVEVISEMFDL
QEPTCLQTRLELYKQGLRGSLTKLKGPLTMMASHYKQHCPPTPETSCAT
QIITFESFKENLKDFLLVIPFDCWEPVQEGAEAAAKEAAAKAGARRGVR
VAWREPGRMELNMPHGQE.
88 . The method of claim 87 , wherein the fusion polypeptide further comprises a purification tag or an export signal peptide.
89 . The method of claim 85 , wherein fusion polypeptide comprises the amino acid sequence:
(SEQ ID NO: 18)
APARSPSPSTQPWEHVNAIQEARRLLNLSRDTAAEMNETVEVISEMFDL
QEPTCLQTRLELYKQGLRGSLTKLKGPLTMMASHYKQHCPPTPETSCAT
QIITFESFKENLKDFLLVIPFDCWEPVQEGSAGSAAGSGARRGVRVAWR
EPGRMELNMPHGQE.
90 . The method of claim 89 , wherein the fusion polypeptide further comprises a purification tag or an export signal peptide.
91 . The method of claim 85 , wherein fusion polypeptide comprises the amino acid sequence:
(SEQ ID NO: 19)
METDTLLLWVLLLWVPGSTGHHHHHHHHHHENLYFQGAPARSPSPSTQPW
EHVNAIQEARRLLNLSRDTAAEMNETVEVISEMFDLQEPTCLQTRLELYK
QGLRGSLTKLKGPLTMIVIASHYKQHCPPTPETSCATQIITFESFKENLK
DFLLVIPFDCWEPVQEGAEAAAKEAAAKAGARRGVRVAWREPGRMELNMP
HGQE.
92 . The method of claim 91 , wherein the fusion polypeptide further comprises a purification tag or an export signal peptide.
93 . The method of claim 85 , wherein fusion polypeptide comprises the amino acid sequence:
(SEQ ID NO: 40)
METDTLLLWVLLLWVPGSTGHHHHHHHHHHENLYFQGAPARSPSPSTQP
WEHVNAIQEARRLLNLSRDTAAEMNETVEVISEWDLQEPTCLQTRLELY
KQGLRGSLTKLKGPLTMMASHYKQHCPPTPETSCATQIITFESFKENLK
DFLLVIPFDCWEPVQEGSAGSAAGSGARRGVRVAWREPGRMELNMPHGQ
E.
94 . The method of claim 93 , wherein the fusion polypeptide further comprises a purification tag or an export signal peptide.
95 . The method of claim 85 , wherein fusion polypeptide comprises the amino acid sequence:
(SEQ ID NO: 36)
METDTLLLWVLLLWVPGSTGHHHHHHHHHHENLYFQGARRGVHVGWREP
GRMELNMPHGGAEAAAKEAAAKAGAPARSPSPSTQPWEHVNAIQEARRL
LNLSRDTAAEMNETVEVISEMFDLQEPTCLQTRLELYKQGLRGSLTKLK
GPLTMMASHYKQHCPPTPETSCATQIITFESFKENLKDFLLVIPFDCWE
PVQE.
96 . The method of claim 95 , wherein the fusion polypeptide further comprises a purification tag or an export signal peptide.
97 . The method of claim 85 , wherein fusion polypeptide comprises the amino acid sequence:
(SEQ ID NO: 39)
RRGVHVGWREPGRMELNMPHGGAEAAAKEAAAKAGAPARSPSPSTQPWE
HVNAIQEARRLLNLSRDTAAEMNETVEVISEWDLQEPTCLQTRLELYKQ
GLRGSLTKLKGPLTMMASHYKQHCPPTPETSCATQIITFESFKENLKDF
LLVIPFDCWEPVQE.
98 . The method of claim 97 , wherein the fusion polypeptide further comprises a purification tag or an export signal peptide.
99 . The method of claim 85 , wherein the infection is selected from the group consisting of a viral infection, a bacterial infection, a protozoal infection, and a fungal infection.
100 . The method of claim 99 , wherein the infection is a viral infection and the virus is selected from the group consisting of hepatitis, human immunodeficiency virus (HIV, e.g., HIV-1), and herpesvirus (e.g., HHV-8).
101 . The method of claim 99 , wherein the infection is a bacterial infection and the bacteria is tuberculosis.
102 . The method of claim 99 , wherein the infection is a protozoal infection and the protozoa is mycoplasma or chlamydia.
103 . The method of claim 99 , wherein the infection is a fungal infection and the fungus is aspergillus.
104 . A method of treating cancer in a subject comprising administering to a subject in need of such treatment a fusion polypeptide comprising an amino acid sequence selected from the group consisting of:
APARSPSPSTQPWEHVNAIQEARRLLNLSRDTAAEMNETVEVISEMFDLQEPTCLQTRLE LYKQGLRGSLTKLKGPLTMMASHYKQHCPPTPETSCATQIITFESFKENLKDFLLVIPFDC WEPVQEGAEAAAKEAAAKAGARRGVRVAWREPGRMELNMPHGQE (SEQ ID NO: 17); APARSPSPSTQPWEHVNAIQEARRLLNLSRDTAAEMNETVEVISEMFDLQEPTCLQTRLE LYKQGLRGSLTKLKGPLTMMASHYKQHCPPTPETSCATQIITFESFKENLKDFLLVIPFDC WEPVQEGSAGSAAGSGARRGVRVAWREPGRMELNMPHGQE (SEQ ID NO: 18); METDTLLLWVLLLWVPGSTGEEFEHTEHTIEEHTEHENLYFQGAPARSPSPSTQPWEHVNAIQE ARRLLNLSRDTAAEMNETVEVISEWDLQEPTCLQTRLELYKQGLRGSLTKLKGPLTMM ASHYKQHCPPTPETSCATQIITFESFKENLKDFLLVIPFDCWEPVQEGAEAAAKEAAAKA GARRGVRVAWREPGRMELNMPHGQE (SEQ ID NO: 19); METDTLLLWVLLLWVPGSTGEEFEHTEHTIRFEFEHENLYFQGAPARSPSPSTQPWEHVNAIQE ARRLLNLSRDTAAEMNETVEVISEWDLQEPTCLQTRLELYKQGLRGSLTKLKGPLTMM ASHYKQHCPPTPETSCATQIITFESFKENLKDFLLVIPFDCWEPVQEGSAGSAAGSGARR GVRVAWREPGRMELNMPHGQE (SEQ ID NO: 40); METDTLLLWVLLLWVPGSTGEEFEHTEHTIRFEFEHENLYFQGARRGVHVGWREPGRMELN MPHGGAEAAAKEAAAKAGAPARSPSPSTQPWEHVNAIQEARRLLNLSRDTAAEMNET VEVISEMFDLQEPTCLQTRLELYKQGLRGSLTKLKGPLTMMASHYKQHCPPTPETSCAT QIITFESFKENLKDFLLVIPFDCWEPVQE (SEQ ID NO: 36); and RRGVHVGWREPGRMELNMPHGGAEAAAKEAAAKAGAPARSPSPSTQPWEHVNAIQEA RRLLNLSRDTAAEMNETVEVISEWDLQEPTCLQTRLELYKQGLRGSLTKLKGPLTMMA SHYKQHCPPTPETSCATQIITFESFKENLKDFLLVIPFDCWEPVQE (SEQ ID NO: 39) in an amount sufficient to treat the cancer.
105 . The method of claim 104 , wherein the fusion polypeptide further comprises a purification tag or an export signal peptide.
106 . The method of claim 104 , wherein fusion polypeptide comprises the amino acid sequence:
(SEQ ID NO: 17)
APARSPSPSTQPWEHVNAIQEARRLLNLSRDTAAEMNETVEVISEMFDL
QEPTCLQTRLELYKQGLRGSLTKLKGPLTMMASHYKQHCPPTPETSCAT
QIITFESFKENLKDFLLVIPFDCWEPVQEGAEAAAKEAAAKAGARRGVR
VAWREPGRMELNMPHGQE.
107 . The method of claim 106 , wherein the fusion polypeptide further comprises a purification tag or an export signal peptide.
108 . The method of claim 104 , wherein fusion polypeptide comprises the amino acid sequence:
(SEQ ID NO: 18)
APARSPSPSTQPWEHVNAIQEARRLLNLSRDTAAEMNETVEVISEMFDL
QEPTCLQTRLELYKQGLRGSLTKLKGPLTMMASHYKQHCPPTPETSCAT
QIITFESFKENLKDFLLVIPFDCWEPVQEGSAGSAAGSGARRGVRVAWR
EPGRMELNMPHGQE.
109 . The method of claim 108 , wherein the fusion polypeptide further comprises a purification tag or an export signal peptide.
110 . The method of claim 104 , wherein fusion polypeptide comprises the amino acid sequence:
(SEQ ID NO: 19)
METDTLLLWVLLLWVPGSTGHHHHHHHHHHENLYFQGAPARSPSPSTQP
WEHVNAIQEARRLLNLSRDTAAEMNETVEVISEWDLQEPTCLQTRLELY
KQGLRGSLTKLKGPLTIMMASHYKQHCPPTPETSCATQIITFESFKENL
KDFLLVIPFDCWEPVQEGAEAAAKEAAAKAGARRGVRVAWREPGRMELN
MPHGQE.
111 . The method of claim 110 , wherein the fusion polypeptide further comprises a purification tag or an export signal peptide.
112 . The method of claim 104 , wherein fusion polypeptide comprises the amino acid sequence:
(SEQ ID NO: 40)
METDTLLLWVLLLWVPGSTGRHHHHHHHHHHENLYFQGAPARSPSPSTQ
PWEHVNAIQEARRLLNLSRDTAAEMNETVEVISEWDLQEPTCLQTRLEL
YKQGLRGSLTKLKGPLTMMASHYKQHCPPTPETSCATQIITFESFKENL
KDFLLVIPFDCWEPVQEGSAGSAAGSGARRGVRVAWREPGRMELNMPHG
QE.
113 . The method of claim 112 , wherein the fusion polypeptide further comprises a purification tag or an export signal peptide.
114 . The method of claim 104 , wherein fusion polypeptide comprises the amino acid sequence:
(SEQ ID NO: 36)
METDTLLLWVLLLWVPGSTGEHHHHHHHHHHEENLYFQGARRGVHVGWR
EPGRMELNMPHGGAEAAAKEAAAKAGAPARSPSPSTQPWEHVNAIQEAR
RLLNLSRDTAAEMNETVEVISEMFDLQEPTCLQTRLELYKQGLRGSLTK
LKGPLTMMASHYKQHCPPTPETSCATQIITFESFKENLKDFLLVIPFDC
WEPVQE.
115 . The method of claim 114 , wherein the fusion polypeptide further comprises a purification tag or an export signal peptide.
116 . The method of claim 104 , wherein fusion polypeptide comprises the amino acid sequence:
(SEQ ID NO: 39)
RRGVHVGWREPGRMELNMPHGGAEAAAKEAAAKAGAPARSPSPSTQPWE
HVNAIQEARRLLNLSRDTAAEMNETVEVISEWDLQEPTCLQTRLELYKQ
GLRGSLTKLKGPLTMMASHYKQHCPPTPETSCATQIITFESFKENLKDF
LLVIPFDCWEPVQE.
117 . The method of claim 116 , wherein the fusion polypeptide further comprises a purification tag or an export signal peptide.Join the waitlist — get patent alerts
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