echemi logo
Product
  • Product
  • Supplier
  • Inquiry
    Home > Active Ingredient News > Drugs Articles > Brief Analysis of Patent Protection of Drug Crystal Forms

    Brief Analysis of Patent Protection of Drug Crystal Forms

    • Last Update: 2021-06-28
    • Source: Internet
    • Author: User
    Search more information of high quality chemicals, good prices and reliable suppliers, visit www.echemi.com
    Drug crystal form research is extremely important in both the development of innovative drugs and generic drugs.




    This mode of operation of the substantive examination actually puts the burden of proof on the applicant more, and the applicant provides evidence to show that the application is novel compared to the comparative documents
    .
    When performing novelty estimation, instruments, testing conditions, purity, solvent residues, etc.
    will all have an impact on the obtained spectrum parameters.
    How to determine whether it is an error or a true difference? When the examiner and the applicant have different opinions, the original Currently, there is no uniform judgment standard in the field, and case analysis is required, combined with common knowledge evidence
    .

    In the re-examination stage, the principles and methods for determining novelty are basically the same as those in the actual examination stage, and the burden of proof remains with the applicant
    .
    The applicant can prove that the crystal protected by this application is different from the crystal disclosed in the comparative document by submitting comparative experimental data
    .

    In the invalidation stage, the judgment principle adopted is different from the actual examination and reexamination.
    The standard of “cannot prove the same, then explain the difference” is adopted.
    In the trial process, the principle of “who asserts, who provides evidence” is adopted.
    If you provide sufficient evidence to support yourself, you need to prove that an invalid patent cannot distinguish another crystal.
    This burden of proof is very difficult, unless you have prepared all the characteristic peaks in the patent you want to invalidate and are protected by the patent.
    Different crystal types of crystals
    .
    Such a difficult burden of proof makes the use of novelty to invalidate the possibility of success
    .

    creativity

    Article 22 of the "Patent Law" stipulates: "Inventiveness" means that compared with the prior art, the invention has outstanding substantive features and significant progress, and the utility model has substantive features and progress
    .


    The "Patent Examination Guidelines" provides general judgment standards for prominent substantive features and judgment standards for significant progress
    .


    Judgment of prominent substantive features: To judge whether an invention has prominent substantive features, it is to judge whether the claimed invention is obvious to those skilled in the art relative to the prior art
    .
    If the claimed invention is obvious compared to the prior art, it does not have prominent substantive features; otherwise, it has prominent substantive features
    .

    Judgment of significant progress: When evaluating whether an invention has made significant progress, the main consideration should be whether the invention has beneficial technical effects
    .


    Three steps to judge creativity

    The three-step method is a general rule for the examination criteria of the inventive step of a chemical invention, which is completed through the following three steps:

    1.
    Determine the closest existing technology;

    2.
    Determine the distinguishing technical features of the invention and the technical problems actually solved by the invention;

    3.
    To determine whether the claimed invention is obvious to those skilled in the art, and if there is enlightenment, it is necessary to determine whether the new technology has produced unexpected technical effects
    .

    Specifically in the field of crystals, different crystals of the same compound may have different physical and chemical properties, including solubility, stability, bioavailability, and so on
    .
    The development of different crystals or amorphous products, hydrates, etc.
    of known compounds to obtain products that are more conducive to industrial production or more suitable for the preparation of pharmaceutical preparations is a common demand in this field, usually through the use of conventional means or the closest existing The similar methods disclosed in the technology can be used to prepare the desired crystal form.
    Although there may be difficulties, the above work can be completed through conventional methods and a limited number of experiments.
    Therefore, those skilled in the art are motivated to develop new crystals.
    Preparation, its technical effect is also predictable
    .
    Therefore, when it comes to the creativity of preparing crystals, it is generally considered to be obvious for combining enlightenment
    .
    To sum up, using the three-step method to determine creativity is actually very likely to ultimately be necessary to determine whether an unexpected technical effect has been produced
    .

    Unexpected technical effects and uses

    The "Patent Examination Guidelines" stipulates that the inventive step of compounds in the chemical field requires that compounds that are structurally similar to known compounds must have unexpected uses or effects
    .
    The unexpected use or effect may be a use different from the known use of the known compound; or it may be a substantial improvement or enhancement of a known effect of the known compound; or it may not be in common knowledge.
    Uses or effects that are clear or cannot be deduced from common sense
    .

    Although it is unpredictable whether a certain compound has a crystal form, how many crystal forms there are, and what kind of crystal form there is, it does exist objectively, and crystals are generally inevitable products obtained by using known crystallization methods for known compounds, namely As long as a certain compound does exist, a crystal can be obtained by using a known crystallization method.
    If a person skilled in the art wants to obtain a crystal of the compound, he does not need to pay creative work to obtain it, unless the compound crystal has unexpected technical effects
    .

    In summary, it can be seen that the key point and difficulty in judging the inventiveness of a drug crystal form patent is actually judging whether the technical effect and use have reached an unpredictable level
    .


    The "Patent Examination Guidelines" stipulates that: Compared with the existing technology, the invention has a "qualitative" change in its technical effect and has new properties; or a "quantity" change that exceeds people's expectations
    .
    Such changes in "quality" and "quantity" cannot be predicted or inferred in advance by those skilled in the art
    .

    Compared with oily or amorphous crystals, they have advantages in terms of taking, weighing, preparing, drying, etc.
    , and the crystal itself is a relatively stable form.
    Therefore, the crystal has better stability and is a well-known crystal in the art.
    Characters, statements of technical effects based on improved stability, generally cannot be considered to have achieved unexpected technical effects
    .
    Secondly, most of the crystals are crystallized from the solution.
    Crystals can further reduce the impurities in the product and improve the purity.
    This is also well-known.
    Therefore, the application of the compound based on the purity is generally not an unexpected technical effect.

    .

    Pharmaceutical crystals can bring about stability, purity, good bioavailability, solubility, storage durability and other technical effects that are known in the art
    .
    When judging whether the above technical effect can reach the "unexpected", it should be fully searched to judge whether the above technical effect has reached the level of significant "quantitative change" that cannot be expected and reasonably introduced for those skilled in the art
    .
    If the technical effect of the crystal is a property other than the common characteristics of conventional crystals, it can be directly judged that the compound crystal has produced a technical effect of "qualitative change", thus possessing creativity
    .
    The description of the above technical effects largely relies on experimental data, so the requirements for experimental data in drug crystal patent applications are generally higher
    .

    For pharmaceutical companies, when applying for a drug crystal form patent, if it is a new compound, it needs to pay attention to the confirmation and preparation of the crystal product, and the requirements for technical effects are relatively low; if it is a compound with a structure that is similar to the known compound in the prior art Close compound", you need to pay attention to the description of the effect of crystal technology
    .


    The key to the success of the creative invalidation request is to find good evidence as the closest existing technology, which makes the patentee need to provide definite evidence to prove that the patent has "unexpected technical effects" in order to successfully defend the rights
    .
    For patentees, this is more difficult, because the technical effects of most crystal patents will not exceed the common technical effects of crystal products
    .
    Therefore, in invalidity, the success rate of choosing creativity as a reason for invalidity is greater than novelty
    .

    Fully open

    Article 26 of the "Patent Law" stipulates that: the specification shall provide a clear and complete description of the invention or utility model, and shall be subject to the realization of the technical personnel in the relevant technical field; when necessary, there shall be drawings
    .


    Sufficient disclosure needs to satisfy the three requirements at the same time, and those skilled in the art can realize the technical solution to solve the technical problem and produce the expected effect according to the content disclosed in the specification
    .


    The specification should describe the composition and crystal structure of the compound crystal, and should record the corresponding physical and chemical parameters that can prove the material composition and microstructure of the crystal; at the same time, the specification should also record at least one preparation method of the compound crystal, so that Those skilled in the art can implement
    .
    If a person skilled in the art cannot confirm the material composition or microstructure of the compound crystal according to the information disclosed in the specification, or cannot be sure whether the compound crystal can be obtained according to the preparation method disclosed in the specification, the specification discloses the compound crystal Not to the extent that those skilled in the art can achieve
    .

    When judging whether the disclosure of the specification is sufficient, the starting point of the judgment is based on the technical solution claimed in the claims to see if the claimed crystalline compound can be obtained
    .
    When there are restrictions on the water content, particle size, melting point, purity, distribution, etc.
    of the crystalline compound in the claims, it is not only necessary to determine whether the preparation method disclosed in the specification can prepare all crystalline products, but also to pay attention to the limited water and other products.
    Materialized state
    .

    In terms of specification disclosure, the most classic example is the disclosure of the embodiment of seed crystal preparation.
    If a seed crystal is used when preparing a new crystal form, but the method of obtaining the seed crystal is not reflected in the specification, in this case, it can be judged Insufficient disclosure
    .
    If the patent applicant wants to explain that the seed crystal used is obtained by a known published method, the novelty of the crystal obtained by crystallization may be questioned
    .
    (Yaodu)

    references:

    1.
    Look at the creativity of drug crystal forms from cases of patent invalidation and administrative litigation
    .
    Chinese Inventions and Patents, No.
    2, 2016, 110-115

    "Patent Protection of Pharmaceutical Crystal Forms" edited by Bai Guangqing

    2.
    Discussion on the novelty of drug crystal form patents
    .
    Zhang Hui et al
    .
    Chinese Journal of New Drugs, 2016, 25(5).

    3.
    Discussion on the creative judgment of drug crystal form patents
    .
    Chinese Inventions and Patents, Issue 5, 2017, 79-81.
    This article is an English version of an article which is originally in the Chinese language on echemi.com and is provided for information purposes only. This website makes no representation or warranty of any kind, either expressed or implied, as to the accuracy, completeness ownership or reliability of the article or any translations thereof. If you have any concerns or complaints relating to the article, please send an email, providing a detailed description of the concern or complaint, to service@echemi.com. A staff member will contact you within 5 working days. Once verified, infringing content will be removed immediately.

    Contact Us

    The source of this page with content of products and services is from Internet, which doesn't represent ECHEMI's opinion. If you have any queries, please write to service@echemi.com. It will be replied within 5 days.

    Moreover, if you find any instances of plagiarism from the page, please send email to service@echemi.com with relevant evidence.