How a Special Enzyme Helps Deliver Immune Drugs Under the Skin

This patent describes a specific, modified human hyaluronidase enzyme that helps the body absorb immune globulin drugs when injected just under the skin, making treatments easier for patients.

What it covers

The patent claims a method for boosting a subject's immune system by injecting immune globulin (IG) and a special soluble hyaluronidase enzyme under the skin. This specific hyaluronidase is a "soluble neutral active human hyaluronidase glycoprotein" (sHASEGP) that works well at the body's neutral pH. It has at least one sugar molecule attached to an asparagine amino acid and is a shortened version of a larger natural enzyme, specifically containing amino acids 36-464 of SEQ ID NO: 1, but truncated at its C-terminus at specific points like amino acid 477 or 483. This enzyme helps the IG spread and absorb better. For example, a patient needing a large dose of immune globulin can receive it as a less painful subcutaneous injection instead of an intravenous infusion, thanks to this enzyme.

What it doesn't cover

• —Does not cover administering hyaluronidase and immune globulin through methods other than subcutaneous injection (e.g., intravenous infusion).
• —Does not cover using this specific hyaluronidase to deliver therapeutic molecules other than immune globulin for immune system modulation.
• —Does not cover hyaluronidase enzymes that contain the complete, full-length amino acid sequence of SEQ ID NO: 1.
• —Does not cover hyaluronidase enzymes that lack the specific asparagine-linked sugar moiety required by the claims.
• —Does not cover hyaluronidase polypeptides with C-terminal truncations outside the specified amino acid residues (e.g., 477-494 of SEQ ID NO: 1) or with less than 95% sequence identity to the claimed truncated forms.

The clever bit

The novelty lies in identifying and engineering a specific, truncated, and glycosylated human hyaluronidase that remains soluble and active at neutral pH, making it ideal for co-administration with other drugs to enhance their subcutaneous absorption.

Why it matters

This technology is important because it makes it possible to deliver large volumes of drugs, like immune globulin, through a simple injection under the skin rather than a lengthy intravenous infusion. This significantly improves convenience and quality of life for patients who require regular treatments. Halozyme, the assignee, has built a platform around this type of enzyme to enable subcutaneous delivery for many different therapeutic areas.

Real-world examples

• 1.Halozyme's ENHANZE drug delivery technology platform
• 2.Herceptin Hylecta (trastuzumab and hyaluronidase-zzxf)
• 3.Phesgo (pertuzumab, trastuzumab, and hyaluronidase-zzxf)
• 4.Darzalex Faspro (daratumumab and hyaluronidase-fihj)
• 5.Hyqvia (immune globulin infusion 10% with recombinant human hyaluronidase)