Log in
E-mail
Password
Remember
Forgot password ?
Become a member for free
Sign up
Sign up
Settings
Settings
Dynamic quotes 

4-Traders Homepage  >  Equities  >  Nasdaq  >  Regeneron Pharmaceuticals Inc    REGN

Delayed Quote. Delayed  - 08/26 10:00:00 pm
402.97 USD   +0.68%
08/22 S&P 500 MOVERS : Mro, regn
08/22 REGENERON PHARM : Announces Agreement with BARDA for the Manufacturi..
08/05DJREGENERON PHARM : Revenue Jumps on Sales of Eye Treatment Eylea -- U..
SummaryQuotesChartsNewsAnalysisCalendarCompanyFinancialsConsensusRevisions 
News SummaryMost relevantAll newsSector news 
The feature you requested does not exist. However, we suggest the following feature:

Regeneron Pharmaceuticals : Patent Issued for Stable Liquid Formulations of Dimer VEGF Antagonists (USPTO 9416167)

share with twitter share with LinkedIn share with facebook
share via e-mail
0
08/25/2016 | 11:07pm CEST

By a News Reporter-Staff News Editor at Angiogenesis Weekly -- A patent by the inventors Dix, Daniel (LaGrangeville, NY); Frye, Kelly (Mendham, NJ); Kautz, Susan (Albany, NY), filed on November 21, 2014, was published online on August 16, 2016, according to news reporting originating from Alexandria, Virginia, by NewsRx correspondents (see also Regeneron Pharmaceuticals, Inc.).

Patent number 9416167 is assigned to Regeneron Pharmaceuticals, Inc. (Tarrytown, NY).

The following quote was obtained by the news editors from the background information supplied by the inventors: "The present invention is directed to pharmaceutical formulations comprising agents capable of inhibiting vascular endothelial growth factor (VEGF), and to methods for making and using such formulations. The invention includes pharmaceutical formulations having increased stability.

"Vascular endothelial growth factor (VEGF) expression is nearly ubiquitous in human cancer, consistent with its role as a key mediator of tumor neoangiogenesis. Blockade of VEGF function, by binding to the molecule or its VEGFR-2 receptor, inhibits growth of implanted tumor cells in multiple different xenograft models (see, for example, Gerber et al. (2000) Cancer Res. 60:6253-6258). A soluble VEGF-specific fusion protein antagonist, termed a 'VEGF trap' has been described (Kim et al. (2002) Proc. Natl. Acad. Sci. USA 99:11399-404; Holash et al. (2002) Proc. Natl. Acad. Sci. USA 99:11393-8), which references are specifically incorporated by reference in their entirety.

"Lyophilization (freeze drying under controlled conditions) is commonly used for long term storage of proteins. The lyophilized protein is substantially resistant to degradation, aggregation, oxidation, and other degenerative processes while in the freeze-dried state (see, for example, U.S. Pat. No. 6,436,897)."

In addition to the background information obtained for this patent, NewsRx journalists also obtained the inventors' summary information for this patent: "Stable formulations of a VEGF-specific fusion protein antagonist are herein provided. The pharmaceutically acceptable formulations of the invention comprise the VEGF 'trap' antagonist with a pharmaceutically acceptable carrier. In specific embodiments, liquid and freeze-dried, or lyophilized formulations are provided.

"In a first aspect, the invention features a stable liquid formulation of a VEGF-specific fusion protein antagonist, comprising a fusion protein comprising a receptor component consisting essentially of an immunoglobulin-like (Ig) domain 2 of a first VEGF receptor and Ig domain 3 of a second VEGF receptor, and a multimerizing component, one or more buffers, and one or more thermal stabilizers. In a specific embodiment of the VEGF-specific fusion protein antagonist, the first VEGF receptor is Flt1 and the second VEGF receptor is Flk1 or Flt4. In a more specific embodiment the fusion protein has the amino acid sequence of SEQ ID NO:2 or SEQ ID NO:4. In one embodiment, the buffer is a phosphate buffer and/or citrate. More preferably, the buffers are phosphate and citrate. In one embodiment, the thermal stabilizers are NaCl and/or sucrose. More preferably, the thermal stabilizers are both NaCl and sucrose.

"In a specific embodiment, the stable liquid formulation of a VEGF-specific fusion protein antagonist comprises 1-10 mM phosphate buffer, 1-10 mM citrate, 25-150 mM NaCl, 5-30% sucrose, 10-50 mg/ml of the fusion protein, at a pH of about 6-6.5. In a more specific embodiment, the stable liquid formulation comprises 5 mM phosphate buffer, 5 mM citrate buffer, 100 mM NaCl, 20% sucrose, 25 mg/ml of the fusion protein, at a pH of about 6.0. Additionally, polysorbate may be present, for example 0.05-0.15% polysorbate 20. The stable liquid formulation of the VEGF-specific fusion protein antagonist of the invention exhibits little or no precipitation after storage of a 25 mg/ml VEGF formulation for about 6 months at -80.degree. C. and little or no precipitation after storage for 6 months at 5.degree. C.

"In a second aspect, the invention features a high concentration stable liquid formulation of a VEGF antagonist comprising 1-50 mM histidine, 25-150 mM NaCl, 5-30% sucrose, 50-100 mg/ml of the fusion protein, at a pH of about 6-6.5, and either 0.1-0.5% polysorbate or 1-5% PEG. In a more specific embodiment, the high concentration stable liquid formulation comprises 10 mM histidine, 50 mM NaCl, 5-20% sucrose, 50-100 mg/ml of the fusion protein, at a pH of about 6.0-6.5, with either 0.1% polysorbate (e.g., polysorbate 20) or 3% PEG (e.g., PEG 3350). The high concentration stable liquid formulation of the VEGF-specific fusion protein antagonist of the invention exhibits less than about 3% degradation after 15 months of storage at 5.degree. C. (75 or 100 mg/ml VEGF trap protein) or less than about 1.5% degradation after 24 months (50 mg/ml).

"In a third aspect, the invention features a pre-lyophilized formulation of a vascular endothelial growth factor (VEGF)-specific fusion protein antagonist, comprising a (i) fusion protein comprising a receptor component consisting essentially of an immunoglobulin-like (Ig) domain 2 of a first VEGF receptor and Ig domain 3 of a second VEGF receptor, and a multimerizing component, (ii) a buffer, (iii) an organic co-solvent or bulking agent, and (iv) one or more lyoprotectants. In various embodiments, the buffer is histidine, the organic co-solvent or bulking agent is PEG, and the lyoprotectant(s) is at least one of glycine and sucrose. In one embodiment, the pre-lyophilized formulation of the invention does not contain a preservative.

"In one embodiment of the pre-lyophilized formulation of the invention, the formulation comprises 5-50 mM histidine, 0.1-3.0% PEG, 0.25-3.0% glycine, 0.5-6.0% sucrose, and 5-75 mg/ml of the fusion protein, at a pH of about 6.0-6.5. In any embodiment, the pre-lyophilized formulation may further comprise up to 0.05 mM citrate and/or 0.003-0.005% polysorbate. The polysorbate present may be, for example, polysorbate 20.

"In a more specific embodiment, the pre-lyophilized formulation comprises about 10 mM histidine, about 1.5% PEG 3350, about 0.75% glycine, about 2.5% sucrose, and about 12.5 to 75 mg/ml VEGF-specific fusion protein, at a pH of about 6.25. In specific embodiments, the fusion protein comprises the protein sequence of SEQ ID NO:4, present as a multimer, e.g., a dimer. In separate embodiments, the reconstituted formulation is 2 times the concentration of the pre-lyophilized formulation, e.g., a 20 mg fusion protein/ml pre-lyophilized formulation is reconstituted to a final formulation of 60 mg fusion protein/ml. Generally, the lyophilized formulation is reconstituted with sterile water suitable for injection. In one embodiment, the reconstitution liquid may be bacteriostatic water.

"In a preferred embodiment, the pre-lyophilized formulation consists essentially of about 10 mM histidine, about 1.5% PEG 3350, about 0.75% glycine, about 2.5% sucrose, and about 50 mg/ml of the fusion protein having the sequence of SEQ ID NO:4 as a dimer, at a pH of about 6.25. Citrate (less than or equal to about 0.02 mM) and/or polysorbate (less than or equal to about 0.0005%) may be present. Optionally, the pre-lyophilized formulation does not contain a preservative, a phosphate buffer, and/or more than trace amounts of NaCl. In one embodiment, the pre-lyophilized formulation consists of about 10 mM histidine, about 1.5% PEG 3350, about 0.75% glycine, about 2.5% sucrose, and about 50 mg/ml of the VEGF trap protein (SEQ ID NO:4), pH 6.3, and upon reconstitution contains 20 mM histidine, 3% PEG, 1.5% glycine, about 5% sucrose, and about 100 mg/ml VEGF trap protein.

"In a fourth aspect, the invention features a method of producing a lyophilized formulation of a VEGF-specific fusion protein antagonist, comprising subjecting the pre-lyophilized formulation of the invention to lyophilization to generate a lyophilized formulation. The lyophilized formulation may be lyophilized by any method known in the art for lyophilizing a liquid.

"In a fifth related aspect, the invention features a method of producing a reconstituted lyophilized formulation of a VEGF-specific fusion protein antagonist, comprising reconstituting the lyophilized formulation of the invention to a reconstituted formulation. In one embodiment, the reconstituted formulation is twice the concentration of the pre-lyophilized formulation, e.g., the method of the invention comprises: (a) producing a pre-lyophilized formulation of a VEGF-specific fusion protein antagonist, (b) subjecting the pre-lyophilized formulation of step (a) to lyophilization; and © reconstituting the lyophilized formulation of step (b).

"In specific embodiments of the method of producing a reconstituted lyophilized formulation, a pre-lyophilized solution is present in a vial as a 25 mg VEGF-specific fusion protein antagonist per ml solution of pre-lyophilized formulation, which is lyophilized and reconstituted to an 50 mg/ml solution. In another embodiment, a 30 mg/ml pre-lyophilized solution is lyophilized and reconstituted to a 60 mg/ml solution. In another embodiment, a 40 mg/ml pre-lyophilized solution is lyophilized and reconstituted to a 80 mg/ml solution. In another embodiment, a 12.5 mg/ml pre-lyophilized solution is lyophilized and reconstituted to a 25 mg/ml solution. In another embodiment, a 50 mg/ml pre-lyophilized solution is lyophilized and reconstituted to a 100 mg/ml solution. In another embodiment, a 75 mg/ml pre-lyophilized solution is lyophilized and reconstituted to a 150 mg/ml solution. Preferably, the reconstituted lyophilized formulation does not contain a preservative.

"Other objects and advantages will become apparent from a review of the ensuing detailed description."

URL and more information on this patent, see: Dix, Daniel; Frye, Kelly; Kautz, Susan. Stable Liquid Formulations of Dimer VEGF Antagonists. U.S. Patent Number 9416167, filed November 21, 2014, and published online on August 16, 2016. Patent URL: http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=9416167.PN.&OS=PN/9416167RS=PN/9416167

Keywords for this news article include: VEGF, Pharmaceutical Company, Regeneron Pharmaceuticals Inc., Anions, Glycine, Alcohols, Histidine, Phosphates, Polysorbates, Fusion Proteins, Protein Kinases, Phosphoric Acids, Membrane Proteins, Organic Chemicals, Cyclic Amino Acids, Angiogenic Proteins, Phosphotransferases, Polyethylene Glycols, Essential Amino Acids.

Our reports deliver fact-based news of research and discoveries from around the world. Copyright 2016, NewsRx LLC

(c) 2016 NewsRx LLC, source Health Newsletters

share with twitter share with LinkedIn share with facebook
share via e-mail
0
Latest news on REGENERON PHARMACEUTICALS
08/25 REGENERON PHARMACEUTICALS : Patent Issued for Stable Liquid Formulations of Dime..
08/25 REGENERON PHARMACEUTICALS : Patent Application Titled "Aseptic Drug Delivery Sys..
08/25 REGENERON PHARMACEUTICALS : Researchers Submit Patent Application, "Shoulder Ada..
08/25 REGENERON PHARMACEUTICALS : Patent Issued for Methods and Compositions for Gener..
08/22 S&P 500 MOVERS : Mro, regn
08/22 REGENERON PHARMACEUTICALS : Announces Agreement with BARDA for the Manufacturing..
08/18 REGENERON PHARMACEUTICALS : Findings from Regeneron Pharmaceuticals Inc. Update ..
08/18 REGENERON PHARMACEUTICALS : U.S. Patents Awarded to Inventors in New Jersey (Aug..
08/18 REGENERON PHARMACEUTICALS : Patent Issued for Promoter-Regulated Differentiation..
08/18 REGENERON PHARMACEUTICALS : Patent Issued for Methods of Inhibiting Tumor Growth..
More news
Sector news : Bio Therapeutic Drugs
08/24DJAMGEN : FDA Rejects Amgen Hormonal-Imbalance Treatment
08/24DJAMGEN : FDA Rejects Amgen Hormonal-Imbalance Treatment
08/23DJDeal for Medivation Is the Latest In a Line of Similar Acquisitions -- WSJ
08/23DJPFIZER : to Acquire Key Drug -- WSJ
08/22DJPfizer's Medivation Deal Latest in Long Line of Similar Acquisitions
More sector news : Bio Therapeutic Drugs
News from SeekingAlpha
08/25 88 Stock Picks For The Next 30 Years (Or More)
08/25 Shocked! Mylan, Biotechs Swoon After Hillary's Statement
08/23 Who's Next After Medivation?
08/22 Amgen undeterred with cholesterol fighter Repatha; 11 abstracts on tap for up..
08/22 Regeneron inks development deal with BARDA for MERS treatment candidates
Advertisement
Financials ($)
Sales 2016 5 062 M
EBIT 2016 1 819 M
Net income 2016 731 M
Finance 2016 961 M
Yield 2016 -
P/E ratio 2016 66,19
P/E ratio 2017 45,41
EV / Sales 2016 8,19x
EV / Sales 2017 6,81x
Capitalization 42 431 M
More Financials
Chart REGENERON PHARMACEUTICALS
Duration : Period :
Regeneron Pharmaceuticals  Technical Analysis Chart | REGN | US75886F1075 | 4-Traders
Full-screen chart
Technical analysis trends REGENERON PHARMAC...
Short TermMid-TermLong Term
TrendsNeutralBullishBearish
Technical analysis
Income Statement Evolution
More Financials
Consensus
Sell
Buy
Mean consensus OUTPERFORM
Number of Analysts 26
Average target price 467 $
Spread / Average Target 16%
Consensus details
EPS Revisions
More Estimates Revisions
Managers
NameTitle
Leonard S. Schleifer President, Chief Executive Officer & Director
P. Roy Vagelos Chairman
Robert E. Landry Chief Financial Officer & Senior VP-Finance
George Damis Yancopoulos Director & Chief Scientific Officer
Neil Stahl Executive VP-Research & Development
More about the company
Sector and Competitors
1st jan.Capitalization (M$)
REGENERON PHARMACEUTIC..-25.77%42 431
AMGEN, INC.5.94%128 696
GILEAD SCIENCES, INC.-21.17%105 269
CELGENE CORPORATION-9.16%84 325
VERTEX PHARMACEUTICALS..-22.84%24 057
ACTELION LTD17.62%18 205
More Results