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Lysosomal targeting of enzymes, and uses thereof
US10556015B2 · US · B2
| Field | Value |
|---|---|
| Publication number | US-10556015-B2 |
| Application number | US-201515521130-A |
| Country | US |
| Kind code | B2 |
| Filing date | Oct 23, 2015 |
| Priority date | Oct 24, 2014 |
| Publication date | Feb 11, 2020 |
| Grant date | Feb 11, 2020 |
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Abstract
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The invention provides compositions and methods for effective lysosomal targeting mediated by PCSK9. In particular, the compositions and methods provided by the invention may be used to treat lysosomal storage diseases such as Pompe Disease and Sanfilippo Syndrome Type B, and they may be used for targeting lysosomal enzymes to the various muscles of the human body.
First claim
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We claim: 1. A targeted therapeutic fusion protein comprising a lysosomal enzyme fused to a lysosomal targeting moiety comprising a proprotein convertase subtilisin kexin type 9 (PCSK9) protein comprising amino acid substitutions S386A and F379A. 2. The targeted therapeutic fusion protein of claim 1 , wherein the lysosomal enzyme is an acid alpha glucosidase (GAA) protein, comprising an amino acid sequence at least 80% identical to SEQ ID NO: 1. 3. The targeted therapeutic fusion protein of claim 1 , wherein the lysosomal enzyme is an alpha-N-acetylglucosaminidase (Naglu) protein comprising an amino acid sequence at least 80% identical to SEQ ID NO: 4. 4. The targeted therapeutic fusion protein of claim 1 , wherein the lysosomal targeting moiety and the lysosomal enzyme are fused via a linker. 5. The targeted therapeutic fusion protein of claim 4 , wherein the linker comprises a sequence of GAPGGGGGAAAAAGGGGGGAPGGGGGAAAAAGGGGGGAPG GGGGAAAAAGGGGGGAP, which is SEQ ID NO: 13.
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Classifications
Dibasic site splicing serine proteases, e.g. kexin (3.4.21.61); furin (3.4.21.75) and other proprotein convertases · CPC title
Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent (peptidic linkers A61K47/65) · CPC title
Stabilising an enzyme by forming an adduct or a composition; Forming enzyme conjugates · CPC title
DNA sequences coding for fusion proteins · CPC title
hydrolysing O- and S- glycosyl compounds (3.2.1) · CPC title
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- What does patent US10556015B2 cover?
- The invention provides compositions and methods for effective lysosomal targeting mediated by PCSK9. In particular, the compositions and methods provided by the invention may be used to treat lysosomal storage diseases such as Pompe Disease and Sanfilippo Syndrome Type B, and they may be used for targeting lysosomal enzymes to the various muscles of the human body.
- Who is the assignee on this patent?
- Shire Human Genetic Therapies, Criteo S A
- What technology area does this patent fall under?
- Primary CPC classification A61K47/65. Mapped technology areas include Human Necessities.
- When was this patent published?
- Publication date Tue Feb 11 2020 00:00:00 GMT+0000 (Coordinated Universal Time) (B2). Legal status and post-grant events are not shown on this page.
- What related patents are in patentsdb?
- We list 8 related publications on this page (citations in our corpus or others sharing the same primary CPC).