Tuesday, 4 July 2017




Novel crystalline forms I, II and III of ponesimod . Useful as a selective sphingosine-1-phosphate receptor-1 (S1P1) receptor agonist, for the treatment of psoriasis. Appears to be first filing from Crystal Pharmatech claiming ponesimod. Johnson & Johnson , following its acquisition of Actelion , is developing ponesimod (phase III clinical trial), a S1P1 agonist, for the treatment of autoimmune disorders. 

Applicants:CRYSTAL PHARMATECH CO., LTD. [CN/CN]; B4-101, Biobay, 218 Xinghu Street,
Suzhou Industrial Park Suzhou, Jiangsu 215123 (CN)
Inventors:CHEN, Minhua; (CN).
ZHANG, Yanfeng; (CN).
LI, Jiaoyang; (CN).
ZHANG, Xiaoyu; (CN)

Most of the family members of the product case ( WO2005054215 ) of ponesimod expire in European countries until November, 2023 and in the US by December, 2024 with US154 extension.

Disclosed are crystalline forms 1, 2, and 3 of a selective S1P1 receptor agonist, namely Ponesimod, and a method for preparing the same. An X-ray powder diffraction pattern of the crystalline form 1 has characteristic peaks at 2 theta values of 18.1° ± 0.2°, 14.6° ± 0.2°, and 11.3° ± 0.2°. An X-ray powder diffraction pattern of the crystalline form 2 has characteristic peaks at 2 theta values of 3.8° ± 0.2°, 10.8° ± 0.2°, and 6.1° ± 0.2°. An X-ray powder diffraction pattern of the crystalline form 3 has characteristic peaks at 2 theta values of 12.2° ± 0.2°, 6.2° ± 0.2°, and 5.6° ± 0.2°. Compared with existing crystalline forms, the present invention has better stability and a greatly increased solubility, and is more suitable for development of a pharmaceutical preparation containing Ponesimod

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Ponesimod (compound of formula I) is a selective S1P1 receptor antagonist developed by Actelion. The drug was used to treat moderate to severe chronic plaque psoriasis in the two medium-term trial was successful, and will carry out the treatment of psoriasis in 3 clinical trials.

The present invention discloses a process for the preparation of a compound of formula I, which is disclosed in patent CN 102177144B, which is an amorphous form prepared by the process of CN100567275C, and discloses a process for the preparation of a compound of formula I, crystalline form C, crystalline form III, Type II. The results show that the crystallinity of crystalline form III is poor and it is converted to crystalline form II at room temperature. The crystalline form II is difficult to repeat and prepare a certain amount of propionic acid. The thermodynamics stability of crystalline form A is inferior to that of crystal form C. In contrast, For the crystal form suitable for the development of the drug, the solubility of the crystalline form C is not ideal.

Example 1
Preparation of Ponesimod Form 1:
48.1 mg of Ponesimod was added to 0.40 mL of 1,4-dioxane and the filtrate was filtered. To the solution was stirred at room temperature, 1.20 mL of n-heptane was added dropwise to precipitate the crystals and stirred overnight. The supernatant was filtered off by centrifugation Liquid to obtain Ponesimod crystal form 1.

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    Follow "'2014' Suzhou International Elite Entrepreneurship Week" with interest Over 88 billion venture capital investment helps your pioneering dreams come true

    Since 2009, there have been 1267 overseas high-level talent projects settled in Suzhou through International Elite Entrepreneurship Week and 54 talents have been introduced and fostered for the national "Thousand Talents Plan". Among these 53 talents, Dr. Chen Minhua, the founder of Suzhou Crystal Pharmatech Co., Ltd., was deeply impressed by thoughtful services in Suzhou for innovative pioneering talents when he recalled the development in Suzhou. "Investment and financing services are placed with particular importance. Everything is thoroughly considered for fear that enterprise
      In 2010, Chen Minhua quitted his job in a well-known pharmaceutical company in the United States and returned with his core 4-people R&D team. He founded Crystal Pharmatech Co., Ltd. in Suzhou Biobay through the Entrepreneurship Week. Till 2013, Crystal Pharmatech has made profits year by year. The yearly output value in 2013 reached 18 million Yuan, while the profits reached as high as 4 million Yuan. His clients involve half of top 20 pharmaceutical companies globally. Chen Minhua longs to fill the vacancy of drug crystals in China and take the lead in the international drug crystal research. Chen Minhua introduced that government service is an integral part to his growth. "Since it was settled down, Suzhou public sector organized several investment and financing activities and offered training and services in various aspects like the mode of financing, finance docking and enterprise strategic investment, which laid a solid foundation for Crystal Pharmatech's capital expansion", said by Chen Minhua.

      To help high-level talents solve financial difficulty, Suzhou lays stress on the docking of science & technology and finance. The person in charge of the Municipal Science and Technology Bureau said that Suzhou guides and integrates social capital for equity investment of hi-tech enterprises at the start-up stage via the guiding funds set up by the government and follow-up investment, etc, thus evolving the venture capital investment cluster based on Shahu Equity Investment Center. After the national "Thousand Talents Plan" venture capital investment center was set up, pioneering talents and venture capital are further converging here. As of the end of 2013, there are 270 effective organizations engaged in various venture capital investment in Suzhou that manage the funds in excess of 88 billion Yuan. 30 million Yuan will be appropriated from the municipal science and technology fund budget for the newly established FOF of Angel Investment this year, so as to take avail of social capital for the development of small and medium-sized hi-tech enterprises.

      Meanwhile, Suzhou sets up the special compensation fund against credit risks and offers "Kedaitong" with "low threshold and low interest rate", so as to solve financial difficulty of small and medium-sized hi-tech enterprises and create favorable financing environment for the pioneering work of talents and corporate development. At present, the fund of credit risk pool has reached 500 million Yuan and "Kedaitong" loans of 8.52 billion Yuan have been granted for 1023 small and medium-sized hi-tech enterprises. Particularly, 120 pioneering enterprises that feature independent intellectual property, high content of technology and light assets were backed up with 1.314 billion Yuan, the special risk compensation fund of "Kedaitong", thus vigorously supporting innovation and pioneering work of leading talents in the science and technology community in Suzhou.

      Reporter Qian Yi
      Quoted from Suzhou Daily on July 6, 2014


Monday, 3 July 2017

Imigliptin dihydrochloride, Xuanzhu Pharma Co Ltd, NEW PATENT, WO 2017107945

Imigliptin dihydrochloride, Xuanzhu Pharma Co Ltd, NEW PATENT, WO 2017107945
Applicants:XUANZHU PHARMA CO.,LTD. [CN/CN]; 2518, Tianchen Street, National High-tech Development Zone Jinan, Shandong 250101 (CN)
Inventors:SHU, Chutian; (CN).
WANG, Zhenhua; (CN)
The present invention relates to a crystalline form of benzoate of a dipeptidyl peptidase-IV inhibitor, a method for preparing the same, a pharmaceutical composition,and a use thereof. Specifically, the present invention relates to a crystalline form of benzoate of a compound used as a dipeptidyl peptidase-IV inhibitor and represented by formula (1), namely (R)-2-((7-(3-aminopiperidine-1-yl)-3,5-dimethyl-2-oxo-2,3-dihydro-1H-imidazo(4,5-b)pyridine-1-yl)methyl)benzonitrile, a method for preparing the same, a pharmaceutical composition, and a use thereof.
Novel crystalline form I of imigliptin dihydrochloride as dipeptidyl peptidase IV inhibitor (DPP-IV) for the treatment of and/or prevention of non-insulin dependent diabetes, hyperglycemia and hyperlipidemia. In June 2017, KBP Biosciences and Xuanzhu Pharma , subsidiaries of Sihuan Pharmaceutical , are developing an imigliptin dihydrochloride (phase II clinical trial), a DPP-IV inhibitor and a hypoglycemic agent,, for the treatment of type II diabetes. Follows on from WO2013007167 , claiming similar composition.
Dipeptidyl peptidase-IV (DPP-IV) inhibitor is a new generation of oral type 2 diabetes treatment drugs, by enhancing the role of intestinal insulin to play a role, non-insulin therapy drugs. Compared with conventional drugs for the treatment of diabetes, DPP-IV inhibitors do not have weight gain and edema and other adverse reactions.
The compound (R) -2 - ((7- (3-aminopiperidin-1-yl) -3,5-dimethyl-2-oxo-2,3-dihydro- 1H-imidazo [4,5-b] pyridin-1-yl) methyl) benzonitrile (described in the specification as a compound of formula (1), as described in patent application PCT / CN2011 / 000068) Inhibitors of compounds, DPP-IV has a strong inhibitory effect and a high selectivity.

The study of crystal form plays an important role in drug development process. Application No. PCT / CN2012 / 078294 discloses the dihydrochloride crystal form I of the compound of formula (1), in order to meet the requirements of formulation, production and transportation , We further studied the crystal form of the compound of formula (1) in order to find a better crystal form.
Example 1 Preparation of benzoate form I of compound of formula (1)
40 g (0.1 mol) of the compound of the formula (1) was added to a 2 L round bottom flask, suspended in 1428 mL of acetonitrile, and the temperature was raised to 60 ° C. The free solution was dissolved, 14.3 g (0.1 mol) of benzoic acid was added, The precipitate was dried at 60 ° C for 1 hour and then allowed to stand at room temperature. The filter cake was dried in vacuo at 40 ° C for 10 hours and weighed 51.6 g in 97.4% yield. By XRPD test, for the benzoate crystal type Ⅰ.

////////////////Imigliptin dihydrochloride, Xuanzhu Pharma Co Ltd, NEW PATENT, WO 2017107945
CFDA Granted Approval of Phase II/III Clinical Trials for Imigliptin Hydrochloride
2016-08-04 15:25:37 Author:admin
        Phase II/ III Clinical Trials of Imigliptin Hydrochloride (KBP-3853) have been approved by CFDA; the Clinical Approval Numbers are 2016L05997 and 2016L06137.
        As we know, in Phase I study both single and multiple doses of Imigliptin Hydrochloride were safe and well tolerated in healthy volunteers and in Type 2 diabetes patients. Imigliptin Hydrochloride demonstrated good pharmacokinetic (PK) characteristics and exhibited dose-proportional plasma exposure. The potent and long duration inhibition of DPP-4 was validated in the PK/PD study. The results of Phase I study of Imigliptin Hydrochloride warranted its long-term safety and efficacy studies in Phase II/ III.
        Currently, the Imigliptin Hydrochloride team has completed the production of clinical trial drug product, as well as finalized the clinical protocols and the study sites. Phase II clinical trial of Imigliptin Hydrochloride will begin in the near future.
       The approval of Imigliptin Hydrochloride for the phase II/ III clinical trials represents another milestone in the SiHuan/ XuanZhu’s new drug discovery history. We enter into a new clinical stage of the development process, and we have many works remaining before us. It is still an urgent task for us to accelerate the clinical development, and to launch the drug product in the China market as soon as possible.

Wednesday, 29 March 2017

QUILSECONAZOLE, VT 1129, New Patent, WO, 2017049080, Viamet

CAS 1809323-18-9

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VT 1129

1340593-70-5 CAS
MF C22 H14 F7 N5 O2, MW 513.37
2-Pyridineethanol, α-(2,4-difluorophenyl)-β,β-difluoro-α-(1H-tetrazol-1-ylmethyl)-5-[4-(trifluoromethoxy)phenyl]-, (αR)-
Viamet, in collaboration with Therapeutics for Rare and Neglected diseases, is investigating quilseconazole benzenesulfonate (VT-1129), a small-molecule lanosterol demethylase (CYP51) inhibitor, developed using the company's Metallophile technology, for treating fungal infections, including Cryptococcus neoformans meningitis.

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Wednesday, 15 March 2017

How to Apply for an International Patent

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How to Apply for an International Patent


Determining the Patentability of your InventionImage titled Apply for an International Patent Step 1

  1. 1Determine if you have a patentable invention. U.S. law sets forth the following requirements for something that can be patented:
    • It must be invented or discovered by a person;
    • It must be a new and useful process, machine, manufacture, or composition of matter; or
    • If not new, it must be an improvement on a useful process, machine, manufacture, or composition of matter.[1]
     Image titled Apply for an International Patent Step 2
    2Verify your invention is not already patented. If your invention meets the requirements for a patentable invention, you must conduct a search to determine whether your idea has already been patented. The US Patent and Trademark Office recommends you follow the following seven steps to search for a patent:
    • Brainstorm terms that are related to your invention. When coming up with terms, think about words relevant to your inventions purpose, make-up, and use.
    • Search for your terms on the USPTO website at: http://www.uspto.gov. You should conduct your search in the following format "CPC Scheme [plus keywords(s) describing invention]." This search should help you locate the invention’s Cooperative Patent Classification (CPC).
    • Once you have located the CPC, review the linked definition to make sure that the definition fits your invention.
    • Search the USPTO patent database, http://appft.uspto.gov, for all patents matching your CPC. After identifying the patents, quickly skim the first page of each patent to determine whether it matches your own invention. If there is a similarity, read the documents more closely including descriptions of the intended use of the invention and any drawings of the invention.
    • If your initial search does not turn up any similar patents, expand your search by performing a key word search on the http://appft.uspto.gov website. You can also search additional databases at http://worldwide.espacenet.com and http://www.uspto.gov/ptrc.[2]
    Image titled Apply for an International Patent Step 3
    3Hire a patent lawyer. Once you have conducted your initial search and found no matching patents, you should hire a patent lawyer. The filing of domestic and international patents requires significant paperwork, legal knowledge of patent law, and experience. While you can attempt to complete the filings yourself, it is strongly advised that you hire someone who has previously applied for patents. This attorney should be able to streamline the process, ensure that you don’t miss any deadlines, and prepare your paperwork so that it meets the requirements.
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Applying for a Patent in Your RegionImage titled Apply for an International Patent Step 4

  1. Determine if you are applying for a provisional or non-provisional patent. A provisional application is essentially a placeholder where you begin to protect your invention before it is a fully formed or completed idea. If you file a provisional application, you will eventually need to file a non-provisional application within one-year of filing the provisional application.
    • A provisional application may be right for you if you are unsure of the commercial value of your invention but you want to protect your invention. It is less expensive to file a a provisional application and you have 12 months to determine if you want to move forward with the cost and time of filing a non-provisional application.
    • If you have already determined the commercial value of your invention and intend to move forward with the production of the product, you should apply for a non-provisional patent and save yourself the time of completing two applications.[3]
    Image titled Apply for an International Patent Step 5
    2Draft a provisional patent application. The provisional patent application provides a less expensive means for applicants filing for U.S. patents. A provisional patent means that the patent is pending. You can file a provisional application without a formal patent claim, oath, declaration, or an information disclosure statement.[4] A provisional patent application must include:
    Image titled Apply for an International Patent Step 6
    3Draft a non-provisional patent application. Unlike the provisional patent application, a patent officer examines a non-provisional patent application and if it meets all of the requirements, a patent will be issued. In order to submit a complete non-provisional patent application, your application must include:
    • A Utility Patent Application Transmittal Form, which lists the required documents for the application and contains the inventor(s) signature or the signature of the inventor’s attorney.
    • A Fee Transmittal Form that specifies the fees that are being submitted with the application.
    • A signed Application Data Sheet that lists inventor and/or applicant information, an address for correspondence, a description of the domestic benefit, and any foreign priority or assignee information.
    • A certification of small and micro entity status, if applicable. If you qualified as a small and micro entity, you must submit one of the following forms: Certification based on gross income or Certification based on institution of higher learning.
    • Any specification documents, which are documents that describe the invention and how it is used. For a full list of specification requirements visit: http://www.uspto.gov/web/offices/pac/mpep/s608.html#d0e44589.
    • All drawings that are necessary to understand the invention.[7]
    • The inventor’s oath or declaration that states the application was made by or on behalf of the inventor, that the invention is believed to be an original invention, and an acknowledgement that any false statement is punishable under the law and by imprisonment. The inventor must sign the document.[8]
    • You can find a link to patent forms at: http://www.uspto.gov/patent/patents-forms.
    Image titled Apply for an International Patent Step 7
    4File your patent with the USPTO. Both provisional and non-provisional applications for patents can be filed in the following ways:

Applying for an International PCT Patent

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Overview of the PCT System
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Comparison of Paris and PCT Route
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Patent Cooperation Treaty (PCT) filing flowchart
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Image titled Apply for an International Patent Step 8

  1. Be mindful of the 12-month deadline for filing an international patent under the Patent Cooperation Treaty. The PCT is an international treaty that allows member countries to file a single international patent application that would be recognized by the other 148 member countries. This patent application must be filed within twelve months of the date that you filed your provisional or non-provisional application with the USTPO.
    Image titled Apply for an International Patent Step 9
    Check foreign country deadlines. Typically, once you submit your PCT patent application you will have between 18 and 30 months to then file your patent in individual countries. This is called “nationalizing” your patent and is discussed below. Before you file your PCT patent, you should be aware of the deadlines so that you can plan your patent application timeline accordingly.[10]
    Image titled Apply for an International Patent Step 10
    Draft a PCT patent application. The PCT patent application requires a number of documents and information for it to be deemed complete. You should consider hiring an attorney that specializes in patent law and is experienced in PCT patents to assist you in drafting your application. Your PCT application must include the following:
    • A PCT Request form that sets forth many of the requirements of the PCT application. The request contains: a petition that the application be processed; the title of the invention; the name of the inventor and/or agent; the inventor’s residence and address; and the inventor’s choice of which international searching agencies he or she wants to conduct the international patent search. The form is located at: http://www.wipo.int/pct/en/forms/
    • The Description must explain the invention in a clear and complete manner. The description should include the following parts: “Technical Field,” “Background Art,” “Disclosure of Invention,” “Brief Description of Drawings,” “Best Mode for Carrying Out the Invention” or, where appropriate “Mode(s) for Carrying Out the Invention,” “Industrial Applicability,” and, if applicable, “Sequence Listing” and “Sequence Listing Free Text.”
    • The Claims section must define the protection that is being sought for the invention.
    • The Drawings section include any technical drawings, perspectives, sections, cross-sections, or other diagrams that are necessary for a reviewer to understand the invention. [11]
    • For applications filed via EFS-Web the application must be in PDF format and on paper size A4.
    • All documents must have a minimum resolution of 300 dpi.[12]
    Image titled Apply for an International Patent Step 11
    File PCT patent application. A PCT patent application can be filed with the International Bureau of the World Intellectual Property Organization (WIPO) in the following ways:
    • Electronically via the ePCT system located at https://pct.wipo.int/LoginForms/epct.jsp; or on the PCT-SAFE system located at http://www.wipo.int/pct-safe/en/.
    • By fax to (41-22) 910 06 10 (or (41-22) 338 70 60 in case of transmission difficulties). You must forward the original document within 14 days to the address listed below.
    • By mail or hand delivery to: International Bureau of WIPO, PCT Receiving Office Section, 34, chemin des Colombettes, 1211 Geneva 20, Switzerland.
    Image titled Apply for an International Patent Step 12
    Pay required fees. In order got your patent application to be reviewed, you must pay the required fees.
    Image titled Apply for an International Patent Step 13
    Wait for international patent search to be conducted. Once you have submitted your PCT application, one of the international patent search companies will perform a patent search and write a report as to the patentability of your invention. If your patent is accepted, your application will be published along with the patentability opinion. You also have the option to withdraw your application.[14]
    Image titled Apply for an International Patent Step 14
    Nationalize your foreign patent. Once you have submitted your application and received a favorable opinion on patentability, you must “nationalize” your PCT application in any country that you want to grant you a patent. For example, if you want France and China to grant you a patent, you must submit your PCT application to each of those countries.
    • As discussed above, each jurisdiction has specific deadlines for when you must nationalize your application. You must file your application before the deadline passes.
    • Typically for nationalization you will have to pay a fee, submit some documentation and potentially translate your application. Since each country has different rules, it is wise to hire a local attorney in the country that you are seeking patent protection. Your U.S. attorney should be able to set up this arrangement and work with local lawyers to ensure the application is filed correctly.
    • You want to nationalize your application where you have expected or actual sales of your invention. The cost for nationalization can run between $4000 and $7000 per country.[15]
    Image titled Apply for an International Patent Step 15
    8  Enforce your patent. If someone uses your patented invention without permission. This is called patent infringement. In order to secure the right to sue for patent infringement, you must have nationalized your patent in the foreign jurisdiction where your patent was used unlawfully.
    • Even though countries may allow a lawsuit for patent infringement, not all countries have the legal mechanisms in place to actually enforce the decision.
    • Certain international treaties, such as the North American Free Trade Agreement (NAFTA) or the International treaties such as the North American Free Trade Agreement (NAFTA) and the Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS), have provisions to enforce patents and provide remedies for patent infringement. However, these treaties are only relevant if the country where the infringement occurred is a party to the treaty.[16]
    • If you believe that your patent was infringed, ask your domestic attorney speak with the local attorney who you used for the nationalization process. They should be able to help you bring a patent enforcement case.

Sources and Citations

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