# US 8,784,833 B2 · Prenatal enzyme replacement therapy for hypophosphatasia

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- Number: US 8,784,833 B2
- Document ID: US8784833B2
- Status: Granted
- Kind: B2
- Application number: 13/007,772
- Filed: 2011-01-17
- Published: 2011-12-08
- Granted: 2014-07-22
- Earliest claimed: 2006-06-27
- Assignees: Saint Louis University
- Applicants: William S. Sly; Jeffrey H. Grubb; Shunjl Tomatsu; Adriana Maria Monta{umlaut over (n)}o Suarez; Hirotaka Oikawa
- Inventors: William S. Sly; Jeffrey H. Grubb; Shunjl Tomatsu; Adriana Maria Monta{umlaut over (n)}o Suarez; Hirotaka Oikawa
- Web page: https://patentgrep.com/patent/US8784833B2

## CPC

- C07K 19/00: Hybrid peptides {, i.e. peptides covalently bound to nucleic acids, or non-covalently bound protein-protein complexes}
- A61K 38/43: Enzymes; Proenzymes; Derivatives thereof
- A61P 3/00: Drugs for disorders of the metabolism (of the blood or the extracellular fluid A61P7/00)
- C12N 9/14: Hydrolases (3)
- C12N 9/2402: {hydrolysing O- and S- glycosyl compounds (3.2.1)}
- C12Y 302/01031: Beta-glucuronidase (3.2.1.31)
- A61K 38/00: Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00)
- C07K 2319/00: Fusion polypeptide
- C07K 2319/30: Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
- Y10S 424/809: involving immunoglobulin or antibody fragment, e.g. fab', fv, fc, heavy chain or light chain
- Y10S 530/866: involving immunoglobulin or antibody fragment, e.g. fab', fab, fv, fc, heavy chain or light chain
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- C12Y: ENZYMES
- Y10S: TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS

## Abstract

Transplacental enzyme replacement therapy (ERT) is disclosed for deficiency of a polypeptide such as a tissue-nonspecific alkaline phosphatase (TNSALP) by administering a pharmaceutical composition that comprises a water-soluble TNSALP portion, e.g., C-terminus-truncated TNSALP peptide-bonded to an IgG1 antibody Fc portion, to a pregnant animal whose fetus or embryo is in need of such therapy. Also contemplated is a method for treating a metabolic disorder, such as HPP, in a fetus or embryo where a fusion protein that comprises a Fc fragment of an IgG1 antibody peptide-bonded to TNSALP is administered to a pregnant mother. The protein crosses the placenta of the mother and enters the fetal blood stream. The protein is taken up into fetal tissue such that the TNSALP restores normal metabolic activity in the fetus.

## Claims

### Claim 1

A method for treating hypophosphatasia in a fetus or embryo comprising the step of parenterally delivering a fusion protein having the sequence as set forth in SEQ ID NO:2 to a pregnant mother, wherein said fusion protein comprises a Fc fragment of an IgG antibody and a tissue-nonspecific alkaline phosphatase enzyme, and wherein said fusion protein crosses a placenta of said mother and enters said fetus's or embryo's blood stream, and wherein said fusion protein is taken up into fetal or embryonic tissue such that said enzyme restores normal mineralization activity in said fetus or embryo.

### Claim 2 (depends on 1)

The method of claim 1, wherein said fusion protein is delivered intraperitoneally or subcutaneously.