The invention disclosed concerns a fixed dose combination (FDC) of pertuzumab, trastuzumab, and, optionally, recombinant human hyaluronidase (rHuPH20), which is administered subcutaneously to patients. The final efficacy and safety data for the FeDeriCa clinical trial, United States Prescribing Information (USPI) (including home-use) methods, and primary analysis of the PHranceSCa clinical trial are disclosed and claimed.

The object of the present invention relates to the new and surprising use of sulfated hyaluronic acid (HAS) as regulator agent of the cytokine activity (pro- and anti-inflammatory) and consequently the use of HAS for the preparation of a new medicine for topic use in the prevention and treatment of pathologies associated with the activation and/or deficiency of cytokines of a pro- and anti-inflammatory nature. The Applicant has in fact discovered the exclusive capacity of HAS in modulating the activity of these particular proteins, it has studied the action mechanism and demonstrated the substantial difference between the different sulfated types known in the state of the art, but above all it has demonstrated an unexpectedly high activity of HAS vs different types and strains of Herpes virus, Cytomegalovirus and the virus of vesicular stomatitis. Finally, a further object of the present invention is the use of HAS as a skin absorption promoter of drugs of an anti-inflammatory nature.

The current invention is a method of treating, preventing, reducing and/or abolishing edema and/or intracranial pressure in a subject by the administration of hyaluronidase. The edema in the brain and intracranial pressure can be the result of a traumatic event, disease or condition including but not limited to a traumatic brain injury, a stroke, a brain tumor, and post-operative swelling.

Disclosed herein are novel compounds, pharmaceutical compositions comprising such compounds and related methods of their use. The compounds described herein are useful, e.g., as liposomal delivery vehicles to facilitate the delivery of encapsulated polynucleotides to target cells and subsequent iransfection of said target cells, and in certain embodiments are characterized as having one or more properties that afford such compounds advantages relative to other similarly classified lipids.

Methods, compositions, and kits are provided for rapidly analyzing microbial growth and/or number in a plurality of water-in-oil emulsion droplets.

Aspects of the disclosure include telomerase inhibitor compositions formulated for subcutaneous administration. Compositions according to certain embodiments include a hyaluronidase enzyme and a telomerase inhibitor having an oligonucleotide and a lipid moiety linked to the 5′ and/or 3′ end of the oligonucleotide. Methods for subcutaneously administering the telomerase inhibitor compositions, such as in the treatment of a neoplasm are also described. Kits having or not having a subcutaneous injector are also provided.

Provided are soluble neutral active Hyaluronidase Glycoproteins (sHASEGP's), methods of manufacture, and their use to facilitate administration for in vitro fertilization, as well as administration of molecules, or to alleviate glycosaminoglycan associated pathologies. Minimally active polypeptide domains of the soluble, neutral active sHASEGP domains are described that include asparagine-linked sugar moieties required for a functional neutral active hyaluronidase domain. Included are modified amino-terminal leader peptides that enhance secretion of sHASEGP. Sialated and pegylated forms of the sHASEGPs also are provided. Methods of treatment by administering sHASEGPs and modified forms thereof also are provided.

The present disclosure provides a method of treating edema in a subject in need thereof, comprising the step of administering a composition that comprises a protein having hyaluronidase activity to a region of the subject having edema.

Modified PH20 hyaluronidase polypeptides, including modified polypeptides that exhibit increased stability and/or increased activity, are provided. Also provided are compositions and formulations and uses thereof.

Disclosed are novel PH20 variants or fragments thereof with improved thermal stability and enzymatic activity of human hyaluronidase, which is an enzyme that hydrolyzes hyaluronic acid, and more particularly novel PH20 variants or fragments thereof including one or more amino acid residue substitutions in the variant having the amino acid sequence of SEQ ID NO: 3, wherein one or more amino acid residues at the N-terminus and/or the C-terminus are optionally further deleted.