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Небесная энциклопедия

Космические корабли и станции, автоматические КА и методы их проектирования, бортовые комплексы управления, системы и средства жизнеобеспечения, особенности технологии производства ракетно-космических систем

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Мониторинг СМИ

Мониторинг СМИ и социальных сетей. Сканирование интернета, новостных сайтов, специализированных контентных площадок на базе мессенджеров. Гибкие настройки фильтров и первоначальных источников.

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Форма поиска

Поддерживает ввод нескольких поисковых фраз (по одной на строку). При поиске обеспечивает поддержку морфологии русского и английского языка
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Применить Всего найдено 74. Отображено 71.
20-01-2022 дата публикации

Orthogonal protein heterodimers

Номер: US20220017579A1
Принадлежит: UNIVERSITY OF WASHINGTON

Disclosed herein are designed heterodimer proteins, monomeric polypeptides capable of forming heterodimer proteins, protein scaffolds including such polypeptides, and methods for using the heterodimer proteins and subunit polypeptides for designing logic gates.

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10-03-2022 дата публикации

De novo design of protein switches for tunable control of protein degradation

Номер: US20220073565A1

Disclosed herein are non-naturally occurring cage polypeptides, kits and degron LOCKRs including the cage polypep-tides, and uses thereof, wherein the cage polypeptides include (a) a helical bundle, comprising between 2 and 7 alpha-helices, wherein the helical bundle includes: (i) a structural region; and (ii) a latch region, wherein the latch region composes a degron located within the latch region, wherein the structural region interacts with the latch region to prevent activity of the degron; and (b) amino acid linkers connecting each alpha helix

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31-03-2022 дата публикации

ORTHOGONAL PROTEIN HETERODIMERS

Номер: US20220098250A1
Принадлежит:

Disclosed herein are designed heterodimer proteins, monomeric polypeptides capable of forming heterodimer proteins, protein scaffolds including such polypeptides, and methods for using the heterodimer proteins and subunit polypeptides for designing logic gates. 1116-. (canceled)117. A cell comprising a designed protein logic gate , wherein: [ (A) each of the dimerizers comprises a fusion of two monomer subunits from different designed heterodimers connected by a polypeptide linker, wherein each of the monomer subunits comprises a binding interface; and', '(B) each of the dimerizers comprises a plurality of hydrophobic residues forming substantially hydrophobic interaction surfaces that regulate the association of the binding interfaces with each other;, '(i) one or more designed dimerizers, wherein, (A) a first effector polypeptide domain; and', '(B) one or more subunits, each subunit comprising a binding interface; and, '(ii) a first designed target monomer comprising, (A) a second effector polypeptide domain, and', '(B) one or more subunits, each subunit comprising a binding interface;, '(iii) a second designed target monomer comprising], '(a) the designed protein logic gate comprises(b) each binding interface of the one or more dimerizers is capable of a binding interaction via its binding interface to the binding interface of (i) another dimerizer, (ii) the first target monomer, or (iii) the second target monomer, wherein the interaction is by an asymmetric hydrogen bond network, to collectively and cooperatively effect gate activation and thereby effect control over a biological function of the cell.118. The cell of wherein the protein logic gate consists essentially of:(i) two dimerizers and the first and second designed target monomers; or(iii) three dimerizers and the first and second designed target monomers.119. The cell of wherein in the absence of binding the first and/or second designed target monomers:(i) each of the one or more dimerizers is in a ...

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12-05-2022 дата публикации

DE NOVO DESIGN OF TUNABLE PH-DRIVEN CONFORMATIONAL SWITCHES

Номер: US20220144895A1
Принадлежит:

Disclosed herein are polypeptides or polypeptide oligomers, including a buried hydrogen bond network that includes at least (1, 2, 3, 4, 5, 6, 7, 8, or 9) pH sensitive amino acids located (i) at an intra-chain interface between different: structural elements in one polypeptide, or (it) at an inter-chain interface between structural elements present in different chains of a polypeptide oligomer, wherein the polypeptide or polypeptide oligomer is stable above a given pH, and wherein the polypeptide or polypeptide oligomer undergoes a conformational transition when subjected to a pH at or below the given pH. 1. A non-naturally occurring polypeptide or polypeptide oligomer , comprising a buried hydrogen bond network that comprises at least 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , or 9 pH sensitive amino acids located (i) at an intra-chain interface between different structural elements in one polypeptide , or (ii) at an inter-chain interface between structural elements present in different chains of a polypeptide oligomer , wherein the polypeptide or polypeptide oligomer is stable above a given pH , and wherein the polypeptide or polypeptide oligomer undergoes a conformational transition when subjected to a pH at or below the given pH.26.-. (canceled)7. The polypeptide or polypeptide oligomer of claim 1 , wherein the buried hydrogen-bond network comprises one or more histidine-containing layers claim 1 , wherein each histidine Nε and Nδ atoms are hydrogen-bonded across the one or more interfaces.89.-. (canceled)10. A non-naturally occurring pH-responsive polypeptide claim 1 , or polypeptide oligomer claim 1 , comprising an oligomeric helical bundle comprising at least four alpha-helical subunits claim 1 , wherein the oligomeric helical bundle comprisesone or more interfaces; andone or more histidine-containing layers that participate in buried hydrogen bond networks, wherein each histidine Ne and NS atoms are hydrogen-bonded across the one or more interfaces;wherein the ...

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08-04-2021 дата публикации

Polypeptides Capable of Forming Homo-Oligomers with Modular Hydrogen Bond Network-Mediated Specificity and Their Design

Номер: US20210101945A1
Принадлежит: UNIVERSITY OF WASHINGTON

Methods and apparatus for identifying and screening hydrogen bond networks are provided. A computing device can determine a search space for hydrogen bond networks related to one or more molecules, where the search space can include a plurality of energy terms related to a plurality of residues related to the hydrogen bond networks. The computing device can search the search space to identify one or more hydrogen bond networks based on the plurality of energy terms. The computing device can screen the identified hydrogen bond networks to identity one or more screened hydrogen bond networks based on scores for the identified hydrogen bond networks. An output can be generated that is related to the one or more screened hydrogen bond networks. Also provided are polypeptides that can form homo-oligomers with modular hydrogen bond network-mediated specificity.

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18-04-2019 дата публикации

Polypeptides Capable of Forming Homo-Oligomers with Modular Hydrogen Bond Network-Mediated Specificity and Their Design

Номер: US20190112345A1

Methods and apparatus for identifying and screening hydrogen bond networks are provided. A computing device can determine a search space for hydrogen bond networks related to one or more molecules, where the search space can include a plurality of energy terms related to a plurality of residues related to the hydrogen bond networks. The computing device can search the search space to identify one or more hydrogen bond networks based on the plurality of energy terms. The computing device can screen the identified hydrogen bond networks to identity one or more screened hydrogen bond networks based on scores for the identified hydrogen bond networks. An output can be generated that is related to the one or more screened hydrogen bond networks. Also provided are polypeptides that can form homo-oligomers with modular hydrogen bond network-mediated specificity.

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01-09-2022 дата публикации

Ultraspecific Cell Targeting Using De Novo Designed Co-Localization Dependent Protein Switches

Номер: US20220273711A1
Принадлежит:

Disclosed am protein switches that can sequester bioactive peptides and/or binding domains, holding them in an inactive (“off”) state, until combined with a second designed polypeptide called die key, which induces a conformational change that activates (“on”) the bioactive peptide or binding domain only when the protein switch components are co-localized when bound to their targets, components of such protein switches, and their use. 1. A method of increasing selectivity of a cell in vitro , ex vivo , or in vivo comprising(a) contacting cells with a first cage polypeptide fused to a first binding domain, wherein the first cage polypeptide comprises (i) a structural region and (ii) a latch region further comprising one or more bioactive peptides, wherein the structural region interacts with the latch region to prevent activity of the one or more bioactive peptides in the absence of colocalization with a key polypeptide and wherein the first binding domain is capable of binding to a first cell moiety present on or within a cell; and(b) contacting the cell with a first key polypeptide fused to a second binding domain, wherein upon colocalization with the first cage polypeptide, the first key polypeptide is capable of binding to the cage structural region to activate the one or more bioactive peptides, wherein the second binding domain is capable of binding to a second cell moiety present on or within the cell,wherein the first cell moiety and the second cell moiety are different or the same.2. The method of claim 1 , wherein the first cell moiety and the second cell moiety are different.3. The method of claim 1 , wherein the first cell moiety and the second cell moiety are the same.4. The method of claim 3 , wherein the colocalization of the first cage polypeptide and the first key polypeptide increases selectivity of an effector toward a cell comprising the first cell moiety and the second cell moiety.5. The method of any one of to claim 3 , wherein the contacting (a ...

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30-07-2020 дата публикации

De novo design of protein switches

Номер: US20200239524A1
Принадлежит: UNIVERSITY OF WASHINGTON

Disclosed are protein switches that can sequester bioactive peptides and/or binding domains, holding them in an inactive (“off”) state, until combined with a second designed polypeptide called the key, which induces a conformational change that activates (“on”) the bioactive peptide or binding domain, components of such protein switches, and their use.

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07-10-2021 дата публикации

Novel Recombinant Cell Surface Markers

Номер: US20210309717A1
Принадлежит: Lyell Immunopharma, Inc.

The present disclosure relates to EGFR-derived polypeptides containing short juxtamembrane sequences, nucleic acids encoding them, and methods of using them to improve cell surface expression of truncated EGFR markers. 1. A recombinant polypeptide comprising an extracellular region , a transmembrane region , and an intracellular region , whereinthe extracellular region comprises a human epidermal growth factor receptor (EGFR) Domain III sequence, andthe intracellular region (i) comprises a juxtamembrane domain that is net-neutral or net-positively charged in the first at least three amino acids (ii) but lacks an active EGFR tyrosine kinase domain.2. The recombinant polypeptide of claim 1 , wherein more than half of the amino acids of the juxtamembrane domain are glycine claim 1 , serine claim 1 , arginine claim 1 , lysine claim 1 , threonine claim 1 , asparagine claim 1 , glutamine claim 1 , aspartic acid claim 1 , glutamic acid claim 1 , tyrosine claim 1 , tryptophan claim 1 , histidine claim 1 , and/or proline.3. The recombinant polypeptide of claim 1 , wherein the amino acid at each position of the juxtamembrane domain is selected according to Table 1.4. The recombinant polypeptide of claim 1 , wherein the juxtamembrane domain comprises RRRHIVRKR (SEQ ID NO:16) claim 1 , RRRHIVRK (SEQ ID NO:17) claim 1 , RRRHIVR (SEQ ID NO:18) claim 1 , RRRHIV (SEQ ID NO:19) claim 1 , RRRHI (SEQ ID NO:20) claim 1 , RRRH (SEQ ID NO:21) claim 1 , RRR claim 1 , RKR claim 1 , or RR.5. The recombinant polypeptide of any one of the preceding claims claim 1 , wherein the intracellular region does not contain any residue that is phosphorylated.6. The recombinant polypeptide of any one of the preceding claims claim 1 , wherein the Domain III sequence comprises SEQ ID NO:2.7. The recombinant polypeptide of any one of the preceding claims claim 1 , wherein the extracellular region further comprises claim 1 , C-terminal to the Domain III sequence claim 1 , (i) a sequence derived from EGFR ...

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25-11-2021 дата публикации

Transmembrane polypeptides

Номер: US20210363214A1
Принадлежит:

De novo designed multi-pass transmembrane polypeptides are described, that include 2 or more transmembrane domains that are each between 15 and 35 amino acids in length, include one or more polar residues, and include at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, or more hydrophobic amino acid residues. 1. A non-naturally occurring polypeptide comprising the general formula X1-TM1-X2-TM2-X3 , whereinX1 is an optional first peptide domainTM1 is a first transmembrane peptide of between 15 and 35 amino acids in length and capable of spanning a biological membrane, wherein (a) the first residue of TM1 is R or K; (b) the last residue of TM1 is W, Y, or L; and (c) at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, or more of the internal residues are hydrophobic;X2 comprises a first connecting peptide;TM2 is a second transmembrane peptide of between 15 and 35 amino acids in length and capable of spanning a biological membrane, wherein (a) the first residue of TM2 is W, T, Q, or Y; (b) the last residue of TM2 is R or K; and (c) at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, or more of the internal residues are hydrophobic; andX3 is an optional second peptide domain;wherein TM1 includes at least a first interior polar amino acid residue that is capable of forming a hydrogen bond with a first interior polar amino acid residue present in TM2.2. The polypeptide of claim 1 , wherein TM1 and TM2 each include at least two interior polar amino acid residues capable of hydrogen bonding with interior amino acids of the other TM domain.35.-. (canceled)6. The polypeptide of claim 1 , wherein TM1 comprises the internal amino acid sequence XXXXX (SEQ ID NO: 1) claim 1 , wherein “X” is any hydrophobic amino acid claim 1 , or wherein TM1 comprises the internal amino acid sequence IFAIVL (SEO ID NO: 2).7. (canceled)9. (canceled)10. The polypeptide of claim 1 , wherein TM2 comprises the amino acid sequence XL(L/V)XXI(L/M)XLVXXI(V/I)X (SEQ ID NO: 15) claim 1 , wherein X is any hydrophobic amino acid ...

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22-03-2023 дата публикации

Chimeric antigen receptor spacers

Номер: EP4149968A1
Принадлежит: Lyell Immunopharma Inc

The present disclosure related to chimeric antigen receptors (CARs) comprising immunoglobulin (Ig) derived spacers, e.g., hinge or loop regions, fragments thereof, or combinations thereof. Ig derived spacer confers improved properties to the CARs, e.g., increased cytokine release with respect the CARs with spacers not derived from hinge regions and fragments thereof, loop regions from constant domains and fragments thereof, and combinations thereof. Also provided are cells expressing CARs comprising Ig derived spacers regions and methods to use the CARs to treat diseases or disorders, e.g., cancer. Some of the disclosed Ig derived spacers are fragments from, e.g., IgA1, IgA2, IgD, IgE, IgG1, IgG2, IgG3, IgG4, or IgM. In some aspects, the disclosed Ig derived spacers are derived from non-human immunoglobulins, e.g., mouse immunoglobulins such IgG2A. Other Ig derived spacer disclosed are modular constructs comprising several concatenated Ig hinges or fragments thereof.

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13-07-2023 дата публикации

Il-12 affinity variants

Номер: WO2023133540A1
Принадлежит: Lyell Immunopharma, Inc., Outpace Bio, Inc.

The present disclosure provides IL-12 affinity variants, pharmaceutical compositions comprising the variants, therapeutic cells expressing the variants, and methods or uses of the same for the treatment or prevention of a disease or disorder.

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29-07-2021 дата публикации

Chimeric polypeptides

Номер: WO2021151006A2
Принадлежит: Outpace Bio, Inc.

The preset disclosure provides chimeric polypeptides comprising a cage polypeptide comprising a degron, wherein the degron is sequestered or caged. Upon activation by a key polypeptide, the degron becomes active. The degron can recruit an ubiquitin ligase and a lysine in the degron or surrounding sequence be ubiquitinated. The ubiquitinated chimeric polypeptide is marked for degradation, together with any biologically active molecule attached to the chimeric polypeptide. The chimeric polypeptides of the present disclosure can be incorporated, for example, to chimeric antigen receptors (CAR). Accordingly, in response to the administration of a key polypeptide or endogenous expression of a key polypeptide mediated, for example, by an inducible promoter, the amount of CAR expressed on the surface of an immune cell can be modulated.

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21-03-2023 дата публикации

CHIMERIC ANTIGEN RECEPTOR SPACERS

Номер: BR112022022953A2
Принадлежит: Lyell Immunopharma Inc

ESPAÇADORES DE RECEPTORES DE ANTÍGENOS QUIMÉRICOS. A presente invenção refere-se a receptores de antígenos quiméricos (CARs) compreendendo espaçadores derivados de imunoglobulina (Ig), por exemplo, regiões de dobradiça ou alça, fragmentos dos mesmos ou combinações dos mesmos. O espaçador derivado de Ig confere propriedades melhoradas aos CARs, por exemplo, elevada liberação de citocinas em relação aos CARs com espaçadores não derivados de regiões de dobradiça e fragmentos dos mesmos, regiões de alça de domínios constantes e fragmentos das mesmas e combinações dos mesmos. Também são fornecidas células que expressam CARs compreendendo regiões de espaçadores derivados de Ig e métodos para usar os CARs para tratar doenças ou distúrbios, por exemplo, câncer. Alguns dos espaçadores derivados de Ig divulgados são fragmentos de, por exemplo, IgA1, IgA2, IgD, IgE, IgG1, IgG2, IgG3, IgG4 ou IgM. Em alguns aspectos, os espaçadores derivados de Ig divulgados são derivados de imunoglobulinas não humanas, por exemplo, imunoglobulinas de camundongo, tal como IgG2A. Outros espaçadores derivados de Ig divulgados são construtos modulares compreendendo várias dobradiças de Ig concatenadas ou fragmentos das mesmas.

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03-01-2024 дата публикации

Ror1 targeting chimeric antigen receptor

Номер: EP4298120A1
Принадлежит: Lyell Immunopharma Inc

The present disclosure relates to polynucleotides encoding a chimeric polypeptide comprising a c-Jun polypeptide, a ROR1-binding protein, and a truncated EGF receptor. Also provided are cells (e.g., T cells) expressing CARs comprising a ROR1-binding protein and overexpressing a c-Jun polypeptide. Overexpression of c-Jun in CAR T cells confers improved properties, e.g., reducing or preventing exhaustion.

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19-11-2020 дата публикации

Ultraspecific cell targeting using de novo designed co-localization dependent protein switches

Номер: WO2020232441A1
Принадлежит: UNIVERSITY OF WASHINGTON

Disclosed am protein switches that can sequester bioactive peptides and/or binding domains, holding them in an inactive (''off'') state, until combined with a second designed polypeptide called die key, which induces a conformational change that activates ("on") the bioactive peptide or binding domain only when the protein switch components are co-localized when bound to their targets, components of such protein switches, and their use.

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20-01-2022 дата публикации

Sars-cov-2 inhibitors

Номер: WO2022015418A1

Polypeptide inhibitors of SARS-CoV-2 are disclosed comprising an amino acid sequence at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence selected from the group consisting of SEQ ID NOS: 1-17, 19-21, 23-34 and 100-101, and their use for treating and limiting development of SARS-CoV-2 infection.

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17-08-2023 дата публикации

Small molecule-regulated cell signaling expression system

Номер: AU2022214455A1
Принадлежит: Outpace Bio Inc

The disclosure provides a first fusion protein comprising a chimeric polypeptide (e.g., a chimeric antigen receptor) and a dimerization domain and a second fusion protein comprising a signaling domain and a dimerization domain, wherein the dimerization domains are capable of forming a dimer and wherein small molecule regulators (e.g., inducers and inhibitors) are capable of altering the state of the dimer to alter the activity of the CAR. Small molecule regulators, cells expressing the fusion proteins of the disclosure, and compositions comprising the proteins, small molecules and cells of the disclosure are provided. Methods of treating or preventing disease or disorders in a subject by providing a composition of the disclosure are described.

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20-07-2023 дата публикации

Designed cytokine compositions and methods of use

Номер: WO2023137346A2
Принадлежит: Outpace Bio, Inc.

The disclosure provides a designed cytokine comprising alpha helices H1, H2, H3, and H4, wherein, from an amino terminus to a carboxy terminus, a first loop (L1) connects H1 and H4; a second loop (L2) connects H4 and H2; a third loop (L3) connects H2 and H3; and wherein the polypeptide binds to IL-2 receptor βγ (IL-2Rβγ).

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13-12-2022 дата публикации

Nuevos marcadores de superficie celular recombinantes.

Номер: MX2022011673A
Принадлежит: Lyell Immunopharma Inc

La presente divulgación se refiere a los polipéptidos derivados del EGFR que contienen secuencias cortas de yuxtamembrana, a los ácidos nucleicos que los codifican, y a los métodos para usarlos con el fin de mejorar la expresión en la superficie celular de los marcadores de EGFR truncados.

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25-01-2024 дата публикации

De novo design of obligate ABC heterotrimeric proteins

Номер: US20240029824A1
Принадлежит: UNIVERSITY OF WASHINGTON

Disclosed are polypeptides having an amino acid sequence at least 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence selected from the group consisting of the amino acid sequences listed in Tables 1, 2, and 3, and heteropolymers formed from such polypeptides.

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06-02-2019 дата публикации

Polypeptides capable of forming homo-oligomers with modular hydrogen bond network-mediated specificity and their design

Номер: EP3436470A1
Принадлежит: UNIVERSITY OF WASHINGTON

Methods and apparatus for identifying and screening hydrogen bond networks are provided. A computing device can determine a search space for hydrogen bond networks related to one or more molecules, where the search space can include a plurality of energy terms related to a plurality of residues related to the hydrogen bond networks. The computing device can search the search space to identify one or more hydrogen bond networks based on the plurality of energy terms. The computing device can screen the identified hydrogen bond networks to identity one or more screened hydrogen bond networks based on scores for the identified hydrogen bond networks. An output can be generated that is related to the one or more screened hydrogen bond networks. Also provided are polypeptides that can form homo-oligomers with modular hydrogen bond network-mediated specificity.

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01-06-2022 дата публикации

モジュラー水素結合ネットワーク介在特異性を有するホモオリゴマーを形成することができるポリペプチドおよびその設計

Номер: JP2022082471A
Принадлежит: UNIVERSITY OF WASHINGTON

【課題】ホモオリゴマーポリペプチドの設計方法を提供する。【解決手段】コンピューティングデバイスは、1または複数の分子に関連する水素結合ネットワークの探索空間を決定し、探索空間は、水素結合ネットワークに関連する複数の残基に関連している複数のエネルギー項を含むことができる。これらの複数のエネルギー項に基づいて、探索空間を探索して1または複数の水素結合ネットワークを特定することができる。特定された水素結合ネットワークのスコアに基づいて、コンピューティングデバイスは、特定された1または複数の水素結合ネットワークを選別し、1または複数の選別された水素結合ネットワークを特定する。1または複数の選別された水素結合ネットワークに関連する出力を生成することができる。また、モジュラー水素結合ネットワーク介在特異性を有するホモオリゴマーを形成することができるポリペプチドを提供する。【選択図】図1

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05-10-2017 дата публикации

Polypeptides capable of forming homo-oligomers with modular hydrogen bond network-mediated specificity and their design

Номер: WO2017173356A1
Принадлежит: UNIVERSITY OF WASHINGTON

Methods and apparatus for identifying and screening hydrogen bond networks are provided. A computing device can determine a search space for hydrogen bond networks related to one or more molecules, where the search space can include a plurality of energy terms related to a plurality of residues related to the hydrogen bond networks. The computing device can search the search space to identify one or more hydrogen bond networks based on the plurality of energy terms. The computing device can screen the identified hydrogen bond networks to identity one or more screened hydrogen bond networks based on scores for the identified hydrogen bond networks. An output can be generated that is related to the one or more screened hydrogen bond networks. Also provided are polypeptides that can form homo-oligomers with modular hydrogen bond network-mediated specificity.

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17-11-2021 дата публикации

De novo design of protein switches for tunable control of protein degradation

Номер: EP3908592A1

Disclosed herein are non-naturally occurring cage polypeptides, kits and degron LOCKRs including the cage polypeptides, and uses thereof, wherein the cage polypeptides include (a) a helical bundle, comprising between 2 and 7 alpha-helices, wherein the helical bundle includes: (i) a structural region; and (ii) a latch region, wherein the latch region composes a degron located within the latch region, wherein the structural region interacts with the latch region to prevent activity of the degron; and (b) amino acid linkers connecting each alpha helix

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13-12-2023 дата публикации

Synthetic degrader system for targeted protein degradation

Номер: EP4288529A2
Принадлежит: Outpace Bio Inc

A fusion protein is provided having a binding element and a degradation initiator, where the binding element selectively binds a target molecule, and the degradation initiator has a sequence isolated or derived from an E3 ligase. A composition is provided comprising: (a) a first fusion protein comprising a first binding element; and (b) a second fusion protein comprising a second binding element; wherein: (1) the first fusion protein further comprises a degradation initiator or a functional variant thereof and the second fusion protein further comprises a target molecule; or (2) the first fusion protein further comprises a target molecule and the second fusion protein further comprises a degradation initiator or a functional variant thereof. The fusion proteins and compositions may be used for the targeted degradation of endogenous and exogenous proteins, optionally, in a cell or in vivo, for the treatment or prevention of a disease or disorder.

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07-05-2020 дата публикации

Orthogonal protein heterodimers

Номер: CA3117841A1
Принадлежит: UNIVERSITY OF WASHINGTON

Disclosed herein are designed heterodimer proteins, monomeric polypeptides capable of forming heterodimer proteins, protein scaffolds including such polypeptides, and methods for using the heterodimer proteins and subunit polypeptides for designing logic gates.

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20-05-2021 дата публикации

Orthogonal protein heterodimers

Номер: AU2019371462A1
Принадлежит: UNIVERSITY OF WASHINGTON

Disclosed herein are designed heterodimer proteins, monomeric polypeptides capable of forming heterodimer proteins, protein scaffolds including such polypeptides, and methods for using the heterodimer proteins and subunit polypeptides for designing logic gates.

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08-09-2021 дата публикации

Orthogonal protein heterodimers

Номер: EP3873919A1
Принадлежит: UNIVERSITY OF WASHINGTON

Disclosed herein are designed heterodimer proteins, monomeric polypeptides capable of forming heterodimer proteins, protein scaffolds including such polypeptides, and methods for using the heterodimer proteins and subunit polypeptides for designing logic gates.

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21-11-2023 дата публикации

Orthogonal protein heterodimers

Номер: US11820800B2
Принадлежит: UNIVERSITY OF WASHINGTON

Disclosed herein are designed heterodimer proteins, monomeric polypeptides capable of forming heterodimer proteins, protein scaffolds including such polypeptides, and methods for using the heterodimer proteins and subunit polypeptides for designing logic gates.

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07-05-2020 дата публикации

Orthogonal protein heterodimers

Номер: WO2020093043A1

Disclosed herein are designed heterodimer proteins, monomeric polypeptides capable of forming heterodimer proteins, protein scaffolds including such polypeptides, and methods for using the heterodimer proteins and subunit polypeptides for designing logic gates.

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01-12-2020 дата публикации

De novo design of protein switches

Номер: US10851135B2
Принадлежит: UNIVERSITY OF WASHINGTON

Disclosed are protein switches that can sequester bioactive peptides and/or binding domains, holding them in an inactive (“off”) state, until combined with a second designed polypeptide called the key, which induces a conformational change that activates (“on”) the bioactive peptide or binding domain, components of such protein switches, and their use.

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16-07-2020 дата публикации

De novo design of protein switches for tunable control of protein degradation

Номер: WO2020146260A1

Disclosed herein are non-naturally occurring cage polypeptides, kits and degron LOCKRs including the cage polypeptides, and uses thereof, wherein the cage polypeptides include (a) a helical bundle, comprising between 2 and 7 alpha-helices, wherein the helical bundle includes: (i) a structural region; and (ii) a latch region, wherein the latch region composes a degron located within the latch region, wherein the structural region interacts with the latch region to prevent activity of the degron; and (b) amino acid linkers connecting each alpha helix

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16-09-2021 дата публикации

Chimeric polypeptides

Номер: WO2021151006A3
Принадлежит: Outpace Bio, Inc.

The preset disclosure provides chimeric polypeptides comprising a cage polypeptide comprising a degron, wherein the degron is sequestered or caged. Upon activation by a key polypeptide, the degron becomes active. The degron can recruit an ubiquitin ligase and a lysine in the degron or surrounding sequence be ubiquitinated. The ubiquitinated chimeric polypeptide is marked for degradation, together with any biologically active molecule attached to the chimeric polypeptide. The chimeric polypeptides of the present disclosure can be incorporated, for example, to chimeric antigen receptors (CAR). Accordingly, in response to the administration of a key polypeptide or endogenous expression of a key polypeptide mediated, for example, by an inducible promoter, the amount of CAR expressed on the surface of an immune cell can be modulated.

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22-10-2020 дата публикации

Amantadine binding protein

Номер: WO2020214679A1
Принадлежит: UNIVERSITY OF WASHINGTON

Disclosed herein are amantadine binding polypeptides, fusion proteins thereof, and uses of such polypeptides and fusion proteins.

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22-02-2023 дата публикации

Espaciadores de receptores de antígenos quiméricos (car).

Номер: MX2022014203A
Принадлежит: Lyell Immunopharma Inc

La presente descripción se refiere a receptores de antígenos quiméricos (CAR) que comprenden espaciadores derivados de inmunoglobulina (Ig), por ejemplo, regiones bisagra o bucle, fragmentos de estas o combinaciones de estas. El espaciador derivado de Ig otorga propiedades mejoradas a los CAR, por ejemplo, mayor liberación de citocinas con respecto a los CAR con espaciadores no derivados de regiones bisagra y fragmentos de estas, regiones de bucle de dominios constantes y fragmentos de estas, y combinaciones de estas. También se proporcionan células que expresan CAR que comprenden regiones espaciadoras derivadas de Ig y métodos para usar los CAR para tratar enfermedades o trastornos, por ejemplo, cáncer. Algunos de los espaciadores derivados de Ig descritos son fragmentos de, por ejemplo, IgA1, IgA2, IgD, IgE, IgG1, IgG2, IgG3, IgG4 o IgM. En algunos aspectos, los espaciadores derivados de Ig descritos derivan de inmunoglobulinas no humanas, por ejemplo, inmunoglobulinas de ratón tales como IgG2A. Otros espaciadores derivados de Ig descritos son construcciones modulares que comprenden varias bisagras de Ig concatenadas o fragmentos de estas.

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19-08-2021 дата публикации

Caged-degron-based molecular feedback circuits and methods of using the same

Номер: AU2020206675A1

Provided are molecular feedback circuits employing caged-degrons. Aspects of such circuits include the use of a caged-degron to modulate the output of a signaling pathway in a feedback-controlled manner. Also provided are nucleic acids encoding molecular circuits and cells containing such nucleic acids. Methods of using caged-degron-based molecular feedback circuits are also provided, including e.g., methods of modulating a signaling pathway of a cell that include genetically modifying the cell with a caged-degron-based molecular feedback circuit.

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16-12-2021 дата публикации

Amantadine binding protein

Номер: AU2020257185A1
Принадлежит: UNIVERSITY OF WASHINGTON

Disclosed herein are amantadine binding polypeptides, fusion proteins thereof, and uses of such polypeptides and fusion proteins.

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23-02-2022 дата публикации

Amantadine binding protein

Номер: EP3956344A1
Принадлежит: UNIVERSITY OF WASHINGTON

Disclosed herein are amantadine binding polypeptides, fusion proteins thereof, and uses of such polypeptides and fusion proteins.

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20-04-2022 дата публикации

De novo design of phosphorylation inducible protein switches (phospho-switches)

Номер: EP3983428A1
Принадлежит: UNIVERSITY OF WASHINGTON

The present disclosure provides a chimeric polypeptide comprising a helical bundle which comprises between about two and about seven alpha-helices and a bioactive peptide, wherein one or more of the alpha helices form one or more inter-helix hydrogen bonds and comprise at least one phosphorylation site and wherein the bioactive peptide is conformationally placed inside the helical bundle so that the bioactive peptide is not activated or exposed. The disclosure also provides a nucleotide sequence encoding the chimeric polypeptide, a vector comprising the nucleotide sequence, a cell comprising the nucleotide sequence, and method of making, using, or designing the chimeric polypeptide.

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19-05-2023 дата публикации

Chimeric antigen receptors

Номер: CA3238005A1
Принадлежит: Outpace Bio Inc

Provided herein are chimeric antigen receptors (CAR) that include a spacer sequence that provides for a cell-to-cell distance between a cell expressing the CAR and a target cell. Embodiments are provided in which an extracellular element of CARs include a spacer sequence, wherein, when the CAR is expressed on the surface of a cell, a cell-to-cell distance between the CAR expressing cell and a target expressing cell is between about 17 nm to about 25 nm, inclusive of the endpoints.

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23-01-2020 дата публикации

De novo design of protein switches

Номер: WO2020018935A2
Принадлежит: UNIVERSITY OF WASHINGTON

Disclosed are protein switches that can sequester bioactive peptides and/or binding domains, holding them in an inactive ("off"') state, until combined with a second designed polypeptide called the key, which induces a conformational change that activates ("on") the bioactive peptide or binding domain, components of such protein switches, and their use.

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05-01-2023 дата публикации

SARS-CoV-2 inhibitors

Номер: AU2021308208A1

Polypeptide inhibitors of SARS-CoV-2 are disclosed comprising an amino acid sequence at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence selected from the group consisting of SEQ ID NOS: 1-17, 19-21, 23-34 and 100-101, and their use for treating and limiting development of SARS-CoV-2 infection.

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29-09-2022 дата публикации

Synthetic degrader system for targeted protein degradation

Номер: WO2022169913A3
Принадлежит: Outpace Bio, Inc.

A fusion protein is provided having a binding element and a degradation initiator, where the binding element selectively binds a target molecule, and the degradation initiator has a sequence isolated or derived from an E3 ligase. A composition is provided comprising: (a) a first fusion protein comprising a first binding element; and (b) a second fusion protein comprising a second binding element; wherein: (1) the first fusion protein further comprises a degradation initiator or a functional variant thereof and the second fusion protein further comprises a target molecule; or (2) the first fusion protein further comprises a target molecule and the second fusion protein further comprises a degradation initiator or a functional variant thereof. The fusion proteins and compositions may be used for the targeted degradation of endogenous and exogenous proteins, optionally, in a cell or in vivo, for the treatment or prevention of a disease or disorder.

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30-05-2024 дата публикации

Chimeric antigen receptors

Номер: AU2022384253A1
Принадлежит: Outpace Bio Inc

Provided herein are chimeric antigen receptors (CAR) that include a spacer sequence that provides for a cell-to-cell distance between a cell expressing the CAR and a target cell. Embodiments are provided in which an extracellular element of CARs include a spacer sequence, wherein, when the CAR is expressed on the surface of a cell, a cell-to-cell distance between the CAR expressing cell and a target expressing cell is between about 17 nm to about 25 nm, inclusive of the endpoints.

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06-12-2023 дата публикации

Small molecule-regulated cell signaling expression system

Номер: EP4284822A1
Принадлежит: Outpace Bio Inc

The disclosure provides a first fusion protein comprising a chimeric polypeptide (e.g., a chimeric antigen receptor) and a dimerization domain and a second fusion protein comprising a signaling domain and a dimerization domain, wherein the dimerization domains are capable of forming a dimer and wherein small molecule regulators (e.g., inducers and inhibitors) are capable of altering the state of the dimer to alter the activity of the CAR. Small molecule regulators, cells expressing the fusion proteins of the disclosure, and compositions comprising the proteins, small molecules and cells of the disclosure are provided. Methods of treating or preventing disease or disorders in a subject by providing a composition of the disclosure are described.

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16-11-2023 дата публикации

Designed cytokine compositions and methods of use

Номер: WO2023137346A3
Принадлежит: Outpace Bio, Inc.

The disclosure provides a designed cytokine comprising alpha helices H1, H2, H3, and H4, wherein, from an amino terminus to a carboxy terminus, a first loop (L1) connects H1 and H4; a second loop (L2) connects H4 and H2; a third loop (L3) connects H2 and H3; and wherein the polypeptide binds to IL-2 receptor βγ (IL-2Rβγ).

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17-11-2021 дата публикации

Caged-degron-based molecular feedback circuits and methods of using the same

Номер: EP3908329A1

Provided are molecular feedback circuits employing caged-degrons. Aspects of such circuits include the use of a caged-degron to modulate the output of a signaling pathway in a feedback-controlled manner. Also provided are nucleic acids encoding molecular circuits and cells containing such nucleic acids. Methods of using caged-degron-based molecular feedback circuits are also provided, including e.g., methods of modulating a signaling pathway of a cell that include genetically modifying the cell with a caged-degron-based molecular feedback circuit.

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24-05-2023 дата публикации

Sars-cov-2 inhibitors

Номер: EP4182027A1

Polypeptide inhibitors of SARS-CoV-2 are disclosed comprising an amino acid sequence at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence selected from the group consisting of SEQ ID NOS: 1-17, 19-21, 23-34 and 100-101, and their use for treating and limiting development of SARS-CoV-2 infection.

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20-01-2022 дата публикации

Sars-cov-2 inhibitors

Номер: CA3181996A1
Принадлежит: Individual

Polypeptide inhibitors of SARS-CoV-2 are disclosed comprising an amino acid sequence at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence selected from the group consisting of SEQ ID NOS: 1-17, 19-21, 23-34 and 100-101, and their use for treating and limiting development of SARS-CoV-2 infection.

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21-04-2022 дата публикации

Caged-degron-based molecular feedback circuits and methods of using the same

Номер: US20220119467A1

Provided are molecular feedback circuits employing caged-degrons. Aspects of such circuits include the use of a caged-degron to modulate the output of a signaling pathway in a feedback-controlled manner. Also provided are nucleic acids encoding molecular circuits and cells containing such nucleic acids. Methods of using caged-degron-based molecular feedback circuits are also provided, including e.g., methods of modulating a signaling pathway of a cell that include genetically modifying the cell with a caged-degron-based molecular feedback circuit.

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19-11-2020 дата публикации

Ultraspecific cell targeting using de novo designed co-localization dependent protein switches

Номер: CA3140172A1
Принадлежит: UNIVERSITY OF WASHINGTON

Disclosed am protein switches that can sequester bioactive peptides and/or binding domains, holding them in an inactive (''off'') state, until combined with a second designed polypeptide called die key, which induces a conformational change that activates ("on") the bioactive peptide or binding domain only when the protein switch components are co-localized when bound to their targets, components of such protein switches, and their use.

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23-03-2022 дата публикации

Ultraspecific cell targeting using de novo designed co-localization dependent protein switches

Номер: EP3969483A1
Принадлежит: UNIVERSITY OF WASHINGTON

Disclosed am protein switches that can sequester bioactive peptides and/or binding domains, holding them in an inactive (''off'') state, until combined with a second designed polypeptide called die key, which induces a conformational change that activates ("on") the bioactive peptide or binding domain only when the protein switch components are co-localized when bound to their targets, components of such protein switches, and their use.

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20-02-2020 дата публикации

De novo design of protein switches

Номер: WO2020018935A3
Принадлежит: UNIVERSITY OF WASHINGTON

Disclosed are protein switches that can sequester bioactive peptides and/or binding domains, holding them in an inactive ("off"') state, until combined with a second designed polypeptide called the key, which induces a conformational change that activates ("on") the bioactive peptide or binding domain, components of such protein switches, and their use.

Подробнее
22-04-2021 дата публикации

De novo design of protein switches

Номер: US20210115090A1
Принадлежит: UNIVERSITY OF WASHINGTON

Disclosed are protein switches that can sequester bioactive peptides and/or binding domains, holding them in an inactive (“off”) state, until combined with a second designed polypeptide called the key, which induces a conformational change that activates (“on”) the bioactive peptide or binding domain, components of such protein switches, and their use.

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24-12-2020 дата публикации

De novo design of phosphorylation inducible protein switches (phospho-switches)

Номер: WO2020257225A1
Принадлежит: UNIVERSITY OF WASHINGTON

The present disclosure provides a chimeric polypeptide comprising a helical bundle which comprises between about two and about seven alpha-helices and a bioactive peptide, wherein one or more of the alpha helices form one or more inter-helix hydrogen bonds and comprise at least one phosphorylation site and wherein the bioactive peptide is conformationally placed inside the helical bundle so that the bioactive peptide is not activated or exposed. The disclosure also provides a nucleotide sequence encoding the chimeric polypeptide, a vector comprising the nucleotide sequence, a cell comprising the nucleotide sequence, and method of making, using, or designing the chimeric polypeptide.

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26-10-2023 дата публикации

Synthetic degrader system for targeted protein degradation

Номер: WO2023150649A3
Принадлежит: Outpace Bio, Inc.

A decoy polypeptide is provided having a dimerization domain binding element that binds to a DHD polypeptide and, optionally, a degradation initiator, where the binding element selectively binds a target molecule, and the degradation initiator. Decoy polypeptides may be used with one or more fusion proteins or compositions comprising same to target endogenous or exogenous proteins in a cell.

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28-03-2024 дата публикации

Orthogonal protein heterodimers

Номер: US20240101615A1
Принадлежит: UNIVERSITY OF WASHINGTON

Disclosed herein are designed heterodimer proteins, monomeric polypeptides capable of forming heterodimer proteins, protein scaffolds including such polypeptides, and methods for using the heterodimer proteins and subunit polypeptides for designing logic gates.

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06-01-2022 дата публикации

Ultraspecific cell targeting using de novo designed co-localization dependent protein switches

Номер: AU2020276307A1
Принадлежит: UNIVERSITY OF WASHINGTON

Disclosed am protein switches that can sequester bioactive peptides and/or binding domains, holding them in an inactive (''off'') state, until combined with a second designed polypeptide called die key, which induces a conformational change that activates ("on") the bioactive peptide or binding domain only when the protein switch components are co-localized when bound to their targets, components of such protein switches, and their use.

Подробнее
23-09-2021 дата публикации

De novo design of protein switches for tunable control of protein degradation

Номер: AU2020207211A9

Disclosed herein are non-naturally occurring cage polypeptides, kits and degron LOCKRs including the cage polypeptides, and uses thereof, wherein the cage polypeptides include (a) a helical bundle, comprising between 2 and 7 alpha-helices, wherein the helical bundle includes: (i) a structural region; and (ii) a latch region, wherein the latch region composes a degron located within the latch region, wherein the structural region interacts with the latch region to prevent activity of the degron; and (b) amino acid linkers connecting each alpha helix

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16-07-2020 дата публикации

De novo design of protein switches for tunable control of protein degradation

Номер: CA3125912A1

Disclosed herein are non-naturally occurring cage polypeptides, kits and degron LOCKRs including the cage polypeptides, and uses thereof, wherein the cage polypeptides include (a) a helical bundle, comprising between 2 and 7 alpha-helices, wherein the helical bundle includes: (i) a structural region; and (ii) a latch region, wherein the latch region composes a degron located within the latch region, wherein the structural region interacts with the latch region to prevent activity of the degron; and (b) amino acid linkers connecting each alpha helix

Подробнее
22-07-2021 дата публикации

De novo design of protein switches for tunable control of protein degradation

Номер: AU2020207211A1

Disclosed herein are non-naturally occurring cage polypeptides, kits and degron LOCKRs including the cage polypeptides, and uses thereof, wherein the cage polypeptides include (a) a helical bundle, comprising between 2 and 7 alpha-helices, wherein the helical bundle includes: (i) a structural region; and (ii) a latch region, wherein the latch region composes a degron located within the latch region, wherein the structural region interacts with the latch region to prevent activity of the degron; and (b) amino acid linkers connecting each alpha helix

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19-11-2020 дата публикации

Lockr-mediated recruitment of car t cells

Номер: CA3140064A1

Disclosed are protein switches that can sequester bioactive peptides and/or binding domains, holding them in an inactive ("off") state, until combined with a second designed polypeptide called the key, which induces a conformational change that activates ("on") the bioactive peptide or binding domain only when the protein switch components are co/localized when bound to their targets, components of such protein switches, and their use.

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11-07-2024 дата публикации

Targeted il-12 affinity variants

Номер: WO2024148369A1
Принадлежит: Lyell Immunopharma, Inc., Outpace Bio, Inc.

The present disclosure provides targeted IL-12 affinity variants, pharmaceutical compositions comprising the variants, therapeutic cells expressing the variants, and methods or uses of the same for the treatment or prevention of a disease or disorder.

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10-08-2023 дата публикации

SARS-COV-2 inhibitors

Номер: US20230250134A1

Polypeptide inhibitors of SARS-COV-2 are disclosed comprising an amino acid sequence at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence selected from the group consisting of SEQ ID NOS: 1-17, 19-21, 23-34 and 100-101, and their use for treating and limiting development of SARS-COV-2 infection.

Подробнее
22-10-2020 дата публикации

De novo design of tunable ph-driven conformational switches

Номер: WO2020215054A1
Принадлежит: UNIVERSITY OF WASHINGTON

Disclosed herein are polypeptides or polypeptide oligomers, including a buried hydrogen bond network that includes at least (1, 2, 3, 4, 5, 6, 7, 8, or 9) pH sensitive amino acids located (i) at an intra-chain interface between different: structural elements in one polypeptide:, or (it) at an inter-chain interface between structural elements present in different chains of a polypeptide oligomer, wherein the polypeptide or polypeptide oligomer is stable above a given pH, and wherein the polypeptide or polypeptide oligomer undergoes a conformational transition when subjected to a pH at or below the given pH.

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06-09-2019 дата публикации

Transmembrane polypeptides

Номер: WO2019169071A1
Принадлежит: UNIVERSITY OF WASHINGTON

De novo designed multi-pass transmembrane polypeptides are described, that include 2 or more transmembrane domains that are each between 15 and 35 amino acids in length, include one or more polar residues, and include at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, or more hydrophobic amino acid residues.

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29-08-2024 дата публикации

Designed cytokine compositions and methods of use

Номер: AU2023208031A1
Принадлежит: Outpace Bio Inc

The disclosure provides a designed cytokine comprising alpha helices H1, H2, H3, and H4, wherein, from an amino terminus to a carboxy terminus, a first loop (L1) connects H1 and H4; a second loop (L2) connects H4 and H2; a third loop (L3) connects H2 and H3; and wherein the polypeptide binds to IL-2 receptor βγ (IL-2Rβγ).

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06-08-2024 дата публикации

Recombinant cell surface markers

Номер: US12054531B2
Принадлежит: Lyell Immunopharma Inc

The present disclosure relates to EGFR-derived polypeptides containing short juxtamembrane sequences, nucleic acids encoding them, and methods of using them to improve cell surface expression of truncated EGFR markers.

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23-09-2024 дата публикации

Composiciones de citocinas dise?adas y metodos de uso.

Номер: MX2024008642A
Принадлежит: Outpace Bio Inc

La divulgación proporciona una citocina diseñada que comprende hélices alfa H1, H2, H3 y H4, en donde, desde un extremo amino hasta un extremo carboxi, un primer bucle (L1) conecta H1 y H4; un segundo bucle (L2) conecta H4 y H2; un tercer bucle (L3) conecta H2 y H3; y en donde el polipéptido se une al receptor de IL-2 ß? (IL-2Rß?).

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