By a News Reporter-Staff News Editor at Pharma Business Week -- From Washington, D.C., NewsRx journalists report that a patent application by the inventors MA, Xinghang (Dublin, CA); XIANG, Jun (Pleasant Hill, CA), filed on August 16, 2017, was made available online on March 8, 2018 (see also Bayer Healthcare LLC).
The patent's assignee is Bayer Healthcare LLC.
News editors obtained the following quote from the background information supplied by the inventors: "The present disclosure relates generally to antibody and other protein formulations that are isosmotic and of low viscosity, including formulations that are useful for injection and general administration.
"Hemophilia patients have bleeding disorders that result in delayed blood clotting after an injury or surgery. Prolonged bleeding is caused by a genetic deficiency in one or more blood clotting factor. Two common types of hemophilia are known--hemophilia A and hemophilia B. Hemophilia A is caused by a deficiency in factor VIII whereas hemophilia B is caused by a deficiency in factor IX. About 75-80% of total hemophilia patients have hemophilia A.
"Tissue factor pathway inhibitor (TFPI) is a human inhibitor of the extrinsic pathway of blood coagulation and functions in anticoagulation. Antibodies that are directed against TFPI, including anti-TFPI monoclonal antibodies (aTFPI mAb), are being developed in an effort to block TFPI function. One such aTFPI mAb is a human IgG2 anti-TFPI mAb. that is being developed for the treatment of hemophilia A and B patients.
"Antibody and other proteins may be administrated to patients via intravenous, intramuscular, and/or subcutaneous injection. To ensure patient compliance, it is desirable that subcutaneous injection dosage forms be isotonic and include small injection volumes (<2.0 ml per injection site). To reduce injection volume, proteins are often administered within the range of 1 mg/ml to 150 mg/ml.
"While both liquid and lyophilized dosage forms are used for currently marketed antibody and other protein-based drug products, lyophilized forms are more frequently used for protein and antibody drug products having high protein concentrations.
"A protein and antibody dosage form may present many challenges in formulation development, especially for liquid formulation. For formulations in which the protein concentration is near its apparent solubility limit, phase separation can occur through precipitation, gelation, and/or crystallization. At high protein concentration, the stability of an antibody or other protein can become problematic due to the formation of soluble and insoluble protein-protein aggregates. Highly concentrated protein formulations are frequently highly viscous, which presents difficulties for processing, such as ultrafiltration and sterile filtration, and for injection of the dosage solution. And at protein concentrations that are desirable for formulations intended for intramuscular or subcutaneous administration, high concentrations of stabilizers, such as sucrose and sodium chloride, are required to achieve long-term protein stability. The resulting hypertonic solutions often cause injection pain due to tissue damage. Therefore, it is critical to balance the amount of stabilizers for stability and osmolality of the high protein concentration formulation.
"For these reasons, there is a need in the art for antibody and other protein-based therapeutic formulations in liquid form that exhibit high protein concentrations without the problem of significantly increased protein aggregation, osmolality, or viscosity and/or decreased protein stability. It is, therefore, desirable that antibody and other protein-based formulations contain limited amounts of excipients and small volumes for ease of therapeutic administration or delivery. It is further desirable that antibody and other protein-based therapeutic formulations be amenable to lyophilization to enhance protein stability under prolonged storage conditions."
As a supplement to the background information on this patent application, NewsRx correspondents also obtained the inventors' summary information for this patent application: "The present disclosure provides liquid and lyophilized antibody and protein-based formulations that are substantially isotonic and low viscosity and that contain substantially no inorganic salt. The antibody and other protein formulations presented herein contain from about 0 mM to about 30 mM histidine; from about 50 ppm to about 200 ppm of a non-ionic surfactant such as, for example, polysorbate (Tween.RTM.) 80 or polysorbate (Tween.RTM.) 20; from about 88 mM to about 292 mM of a sugar or sugar alcohol such as, for example, mannitol, dextrose, glucose, trehalose, and/or sucrose; from about 0 mM to about 50 mM arginine; from about 0 mM to about 50 mM lysine; from about 0 mM to about 133 mM glycine or alanine; from about 0 mM to about 10 mM methionine; and from about 1 mg/ml to about 150 mg/ml of a protein at a pH from about pH 4.0 to about pH 6.0. The formulations disclosed herein exhibit a viscosity ranging from about 1 mPa-S to about 20 mPa-S at 22.degree. C., or from about 1 mPa-S to about 15 mPa-S at 22.degree. C., or from about 1 mPa-S to about 10 mPa-S at 22.degree. C. or from about 1 mPa-S to about 8 mPa-S at 22.degree. C. or from about 1 mPa-S to about 6 mPa-S at 22.degree. C. and osmolality ranging from about 240 to about 380 mmol/kg.
"Within further aspects, the present disclosure provides methods for the treatment of a disorder in a patient, comprising the administration to the patient of a therapeutically effective amount of one or more formulations described herein. For example, provided are methods for the treatment of a disorder in a patient, comprising the administration to the patient of a therapeutically effective amount of an antibody or other protein formulation as described in greater detail herein.
"These and other features of the present teachings are set forth herein."
For additional information on this patent application, see: MA, Xinghang; XIANG, Jun. Antibody and Protein Formulations. Filed August 16, 2017 and posted March 8, 2018. Patent URL: http://appft.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PG01&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.html&r=1&f=G&l=50&s1=%2220180055940%22.PGNR.&OS=DN/20180055940&RS=DN/20180055940
Keywords for this news article include: Antibodies, Business, Hemophilia, Immunology, Bayer Group, Therapeutics, Blood Proteins, Immunoglobulins, Drugs and Therapies, Health and Medicine, Bayer Healthcare LLC, Healthcare Companies, Subcutaneous Injections, Hematologic Diseases and Conditions.
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