Author Archives: David Rucando

Trippy Synthesis of Salvinorin A Analog

September 15, 2017

Scripps and USC researchers report a 10-step synthesis of 20-norsalvinorin A.

Improved synthesis should help chemists to invent new salvinorin A analogs to sidestep its psychoactive effects while preserving its analgesic effects. Salvinorin A, a hallucinogen produced by the plant Salvia divinorum, is promising for treating itch and pain by activating the kappa-opioid receptor while avoiding the mu-opioid receptor, which has been associated with opioid abuse.

So far Scripps has a few patents and applications directed to other classes of Kappa Opioid ligands.

US9,682,966 Kappa Opioid Ligands
US9,345,703 Kappa Opioid Receptor Effectors and Uses Thereof
US2016/0257685 Kappa Opioid Receptor Effectors and Uses Thereof
US2015/0210673 Kappa Opioid Ligands

Probably a few new patent applications are in the works. I haven’t seen any patent publications yet.

Salvinorin A & 20-Norsalvinorin

Salvinorin A & 20-Norsalvinorin

Link to C&E News Science Concentrated Article:

“Synthetic simplification of hallucinogen pays off” 

Onglyza® and Kombiglyze® XR (saxagliptin) Patent Survives Challenge from Mylan

September 12, 2017

Mylan and other generic manufacturers petitioned the Patent Trial and Appeal Board (PTAB) to institute an inter partes review of AstraZeneca’s patent claiming compositions including saxagliptin. AstraZeneca markets saxagliptin as Onglyza® and Kombiglyze® XR for diabetes.

Case IPR2015-01340 / Patent RE44,186 E

The PTAB’s Administrative Patent Judges (APJ) decided that the petitioners did not show with preponderance of the evidence that the claims of Reissue RE44,186 of U.S. Patent No. 6,395,767 would have been obvious to a skilled artisan.  Particularly, saxagliptin was not obvious over “compound 25.”

Saxagliptin:

Saxagliptin Structure

Saxagliptin Structure

Prior art: “Compound 25”

Structure of Prior Art "Compound-25"

Structure of “Compound-25”

State of the Art:

Experienced medicinal chemists (Persons of Ordinary Skill in the Art [PHOSITA]) knew saxagliptin bound to DP 4.  But they did not have detailed knowledge of DP 4’s active site for guidance in designing inhibitors because DP 4’s crystalline structure was unknown. At the time of invention, knowledge of DP 4’s binding requirements came from structure-activity relationship (“SAR”) studies.

Lead Compound Analysis:

Petitioners cited a publication by Ashworth containing Compound-25, which they argued would have been selected as a lead compound. (Ashworth et al., 2-“Cyanopyrrolidides as Potent, Stable Inhibitors of Dipeptidyl Peptidase IV,” 6(10) Bioorganic &Med. Chem. Lett., 1163–66 (1996)).

“Compound-25” would not have been selected as a lead compound

The PTAB reasoned that a medicinal chemist would not have selected compound 25 as a lead compound because, among other reasons, (i) Compound 25 was only one of several other similar compounds (ii) Compound 25 only had in vitro data obtained using non-physiological conditions, (ii) there were two much more advanced compounds in clinical trials (i.e., NVP-DPP728 & P32/98) and (iii) Ashworth’s subsequent publication focused on different series of compounds.

NVP-DPP728 & P32/98

Clinical Compounds NVP-DPP728 & P32/98

The PTAB’s analysis could have ended there. But even accepting Petitioners’ assertion that a skilled artisan would have chosen compound 25 as a lead compound, the PTAB determined that the Petitioners didn’t demonstrate that a skilled artisan would have had reason to modify compound 25 with a reasonable expectation of success to arrive at the claimed saxagliptin.

Check out PatentDocs’s Post for further discussion:

http://www.patentdocs.org/2017/09/mylan-pharm-v-astrazeneca-ab-ptab-2017.html

 

 

The Fastest USPTO Technology Center is 1620 – Organic Chemistry!

August 15, 2017

USPTO Technology Center 1620 has the shortest delay before sending an Office Action.

According to the Official Gazette, TC1620 has a <18-month delay.*

* Numbers include RCE reworks that substantially reduce the delay of organic chemistry patent applications.

The Average filing date for an organic chemistry patent application receiving an office action in the last 3-months is November 15, 2015.†

† Report last updated on June 30, 2017.

See also: PatentlyO Post

 

Velcade® Patent Validated by CAFC

August 8, 2017

Millennium Pharmaceuticals, Inc. v. Sandoz Inc. (Fed. Cir. 2017)

A Court of Appeals for the Federal Circuit (CAFC) panel reversed the district court’s holding that Millennium’s licensed patent, U.S. Patent No. 6,713,446 (“the ‘446 Patent”) was invalid for being obvious. The ‘446 Patent claimed a lyophilized mannitol ester prodrug of Bortezomib (See Claim 20). Claim 20 was not obvious according to the panel because, among other reasons, the inventors unexpectedly “discovered that the reason for the dramatic improvement in dissolution and stability for this formulation was the formation of a new chemical compound during lyophilization: the claimed ester of bortezomib and mannitol.”

  • Claim 20:  The lyophilized compound D-mannitol N-(2-pyrazine)carbonyl-L-phenylalanine-L-leucine boronate.

Earlier, the district court concluded that the new compound was obvious reasoning that Bortezomib was already known (U.S. Patent No. 5,780,454), Lyophilization is already known known, and that the claimed compound is “the inherent result of an allegedly obvious process” of  lyophilizing bortezomib and mannitol together.

  • There was no evidence that anyone “foresaw, or expected, or would have intended, the reaction between bortezomib and mannitol, or that the resulting ester would have the long-sought properties and advantages”
  • “The district court did not find that the prior art taught or suggested that the claimed new compound would be formed, or taught or suggested making the claimed new compound by any method, or taught or suggested that this new compound would have the properties of stability, solubility, and dissociability that it exhibited.”
  • “No reference taught or suggested reacting bortezomib with mannitol, and no reference hinted that such an esterification reaction might occur during lyophilization.”
  • “No reference taught or suggested that the product of such lyophilization would be a new chemical compound that would solve the problems that had inhibited development of bortezomib in oncology.”
IP Watchdog Post by Jay Pattumudi:
http://www.ipwatchdog.com/2017/08/10/inherent-obviousness-motivation-modify-lead-compound-surprising-unexpected-results/id=86661/
Patent Docs Post:
http://www.patentdocs.org/2017/07/millennium-pharmaceuticals-inc-v-sandoz-inc-fed-cir-2017.html
Dilworth IP Post:
http://www.dilworthip.com/nonobviousness-push-back-millennium-pharma-v-sandoz/
VELCADE® Prescribing Information:
http://www.velcade.com/Files/PDFs/VELCADE_PRESCRIBING_INFORMATION.pdf
VELCADE® (bortezomib) Official Website:
http://www.velcade.com/

SCOTUS Opinion on Patent Exhaustion

June 2, 2017

The Supreme Court Tuesday issued its decision on patent exhaustion on Tuesday May 30, 2017. (Impression Products, Inc. v. Lexmark International, Inc.)

Below are a few blog posts for reading.

Supreme Court Holds Patent Exhaustion is Not Limited to U.S. Sales

Supreme Court Holds that Any Sale of a Patented Product Exhausts Patent Holder’s Rights

U.S. Supreme Court Significantly Restricts Patent Owners’ Ability to Control Resale of Patented Items

 

Carbon Black

For the Interesting Patents file:

C&EN recently published an interesting article on Orion Engineered Carbons GbmH and its strategy of making and selling the most sophisticated grades of carbon black it can.

Carbon Black is a is a material produced by the incomplete combustion of heavy petroleum products. It is widely used as reinforcing filler material for rubber.   [Tires, tire treads, cable sheathing, hoses, drive belts, conveyor belts, roll coverings, shoe soles, sealing rings, profiles, and damping elements.]  Carbon black is also used as a pigment. That’s not surprising given its name.

A recent carbon black patent issued to Orion is US 8,735,488.

US 8,735,488

Claim 1.  A carbon black, characterized in that the CTAB surface area is from 100 to 160 m2/g, the quartile ratio is greater than 1.60, and the FP index is >0.

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