China: How To Judge Inventiveness Of A Crystalline Compound Boehringer Ingelheim Pharma Gmbh & Co.KG V. Patent Reexamination Board

Crystalline Monohydrate of Tiotropium Bromide

Boehringer Ingelheim Pharma GmbH & Co.KG v. the Patent Reexamination Board- How to Judge Inventiveness of a Crystalline Compound (Administrative Ruling (2012)Xing Zhi ZiNo. 86 by the Supreme People's Court on November 27, 2012)

With reference to inventive step of compound claims, it is stipulated in the Guidelines for Patent Examination that for a compound NOT similar in structure to a known compound, it will be regarded as inventive when it has a certain use or effect where a compound that IS similar in structure to a known compound, it might be regarded as inventive only if it has an unexpected use or effect. As can be seen, it is important to judge whether a compound is structurally similar to a known compound. This case clarifies that in the determination of inventiveness of a crystalline compound, the wording "structurally similar compounds" specifically refers to compounds having the same central part or basic ring, and has nothing to do with comparison between microcrystalline structures. The microcrystalline structure difference shall be considered only if it brings unexpected technical effect.

The petitioner Boehringer Ingelheim Pharma GmbH & Co.KG(hereinafter referred as "BIPG") challenged the validation of the patent No. ZL 01817143.5 titled "Crystalline monohydrate, method for producing the same and the use thereof in the production of a medicament" (hereinafter referred as "The challenged patent") for lacking an inventive step in view of Evidence 5a and Evidence 1. Evidence 5a discloses Tiotropium Bromide X-hydrate. Evidence 1 discloses Tiotropium Bromide crystals.

To defend against the petitioner, the Patentee provided Counter-evidence 1, the Observation as submitted in response to the first office Action, to prove the unexpected technical effect that "after micronizing, the crystalline Tiotropium Bromide monohydrate of claim 1 produces substantially stable sub-particles under pressure."

The Patent Reexamination Board ("PRB" hereinafter) ascertained that the chemical product of claim 1 and the chemical products of Evidence 5a and Evidence 1 have the same main portion, i.e. Tritropium Bromide. In other words, the chemical products of claim 1, Evidence 5a and Evidence 1 have the same structure of Tiotropium Bromide as their central part. Therefore these three products are structurally similar to each other. For use of a chemical product and its technical effects, it is only generally mentioned in the description of the challenged patent that the claimed pharmaceutically active substance will meet some demanding requirements, but there is no evidence proving such technical effects. Therefore, the product of claim 1 cannot be considered as having any unexpected technical effect over the prior art, such as Evidence 5a or Evidence 1. Thus, claim 1 should be invalidated.

The first and the second instance courts upheld the PRB's view as mentioned above.

The Patentee submitted a request to the Supreme People's Court for retrial, indicating that (1) crystalline Tiotropium Bromide monohydrate of claim 1, Tiotropium Bromide X-hydrate of Evidence 5a, and Tiotropium Bromide crystal of Evidence 1 are not "structurally similar compounds" mentioned in the Guidelines for Patent Examination; and (2) the Counter-evidence has proved an unexpected effect, i.e. particle size of the micronized sub-particles remained unchanged under pressure.

Upon hearing, the Supreme People's Court holds that this case focuses on whether the monohydrate crystals of the challenged patent, the anhydrous crystal of Evidence 1 and x-hydrate of Evidence 5a are "structurally similar compounds" stipulated in the Guidelines for Patent Examination, and whether an unexpected technical effect is achieved in the challenged patent.

In this regard, the judge ascertained that crystalline compounds have diverse microscopic crystal structures. In a solid state, a certain compound may have different solid crystalline forms based on two or more different molecular arrangement, but not all of the microscopic crystal structures would necessarily lead to prominent substantive features and produce a notable progress. Therefore, crystalline compounds cannot be considered as "not similar in structure with each other" only due to their different microscopic crystal structures. While judging inventiveness of a crystalline compound, its microscopic crystal structure shall be considered in combination with the question whether it brings in unexpected technical effects. Furthermore, the judge ascertained that the crystalline monohydrate as claimed does not have any unexpected technical effect according to the description of the challenged patent.

Based on the above affirmation, the crystalline Tiotropium Bromide monohydrate of claim 1 are similar in structure with the prior art chemical products, and there is no description showing that the crystalline monohydrate as claimed produces an unexpected technical effect over the prior art. Thus, the Supreme People's Court rejected the patentee's request for retrial.


In the field of pharmaceutical chemistry, developments of new pharmaceutical active compounds is always expensive. In contrast, screening new crystalline form of known chemical products is much cost-friendly. Meanwhile, patents of new crystal form do a good job in extending market exclusivity period of patent medicines. Therefore, in order to extend the patent protection period in a different way, patentee of a compound patent often desires to get patent for new crystal form of the known compound.

However, compared with a known pharmaceutically active compound, these crystalline forms generally only differ in their microscopic crystal forms, without significant change in their basic chemical composition. Considering that the crystalline form of a compound would necessarily have "a certain use and effect," if such a crystalline compound was considered as having different structure with the known compound, it should be granted a patent right. This criterion will inevitably result in a flood of crystalline compound patents, thereby discourage people's enthusiasm to invent. This is contrary to the legislative intent of the Chinese patent law "to encourage inventions".

In the present case, the Supreme people's Court clarified criteria to judge the inventive step of a crystalline compound invention. A crystalline compound invention should only be considered as inventive if its distinguishing microcrystalline structure results in unexpected technical effect. As can be seen, "unexpected technical effect" is a prerequisite to grant patent to a new crystal form of a known compound.

An active compound may have diverse crystal forms, and one or more of them would necessarily have superior technical effects over others. How to determine whether these superior technical effects are so-called unexpected technical effect? Chapter 4, Part II of the Guidelines for Patent Examination has the following stipulations: the unexpected technical effect means that as compared with the prior art, the technical effect of the invention represents a "qualitative" change, that is, new performance; or represents a "quantitative" change which is unexpected. Such a qualitative or quantitative change cannot be expected or inferred by person skilled in the art in advance. As can be seen, unpredictivity of a technical effect would be critical to determine whether it is unexpected.

Back to the present case, crystalline compound is a compound wherein molecules are spatially arranged in a periodic and repeated way according to certain rules. Therefore, crystal form of a compound necessarily has better thermal stability when compared with its amorphous form. Claim 1 relates to crystalline Tiotropium Bromide monohydrate wherein the crystalline hydrate molecule are arranged periodically and interact with each other with certain forces. Compared with the crystalline hydrate, amorphous hydrate wherein water molecules are arranged irregularly are easier to lose their water. That is to say, the technical effect that "the crystalline monohydrate does not start to dehydrate until the temperature rises to 50℃and thus it may be stored for a long-term at room temperature or under even more severe conditions" is foreseeable. Therefore, the above technical effect cannot be considered as an "unexpected" technical effect.

The challenged patent may be maintained valid, if (1) the patentee had documented the effects that "after micronizing, the crystalline Tiotropium Bromide monohydrate produce substantially stable sub-particles under pressure"; and (2) relevant experimental data had been provided to support the above technical effect. As far as the writer's knowledge, there is no necessary correlation between the stability of particle size and the crystal structure of a compound. That is to say, the technical effect of "stable particle size" seems to be unpredictable and cannot be reasonably inferred, and thus can be considered as an unexpected technical effect. Thus, the relevance between technical effects and structural features is an important element to be considered. Therefore, it would be necessary to deeply study the structure-effect relationships.

In the writer's opinion, it is necessary to include and draft several technical effects produced by an invention in a clear, justified, and progressive manner in the description. One or more of these beneficial technical effects might be deemed to be unexpected technical effects in further examination or litigation proceedings when facing inventiveness challenges, so that the applicant will occupy a favorable position.

First of all, description on an unexpected technical effect should be clear and justified. The description should clearly illustrate which particular technical effects are beneficial over the prior art. For this case, "the activity stability of the starting materials under various environmental conditions, the stability during production of the pharmaceutical formulation, and the stability of the final medicament composition" are only generally and ambiguously mentioned in the last paragraph on page 1. This vague and general description is meaningless to prove an unexpected technical effect. In the field of pharmaceutical chemistry, necessary experiment data is usually pre-requisite to verify beneficial effects.

Second, it is better to draft beneficial technical effects in a progressive (pyramidal) manner so as to build a "pool" for unexpected technical effect. The drafter should not only understand the invention extensively as a whole, but also draft related technologies in a progressive way, so as to set up multiple "layers" of protection. For example, the patentee of the challenged patent unerringly further limits "stability during production of the pharmaceutical formulation" to "stability of amorphous configuration and crystal lattice" in paragraph 5, page 2 of the description. Unfortunately, the stability of amorphous configuration and crystal lattice were not considered, since the prior art Tritropium Brominate has better crystalline configuration and lattice stability.

In summary, in order to obtain a more stable patent, the patentee should assess all risks that may occur in the future, set forth in the specification a variety of beneficial technical effects, and provide strong support to such effects via adequate experimental data, so as to better safeguard the patent application/right.

The content of this article is intended to provide a general guide to the subject matter. Specialist advice should be sought about your specific circumstances.

To print this article, all you need is to be registered on

Click to Login as an existing user or Register so you can print this article.

Similar Articles
Relevancy Powered by MondaqAI
Some comments from our readers…
“The articles are extremely timely and highly applicable”
“I often find critical information not available elsewhere”
“As in-house counsel, Mondaq’s service is of great value”

Related Topics
Similar Articles
Relevancy Powered by MondaqAI
Related Articles
Related Video
Up-coming Events Search
Font Size:
Mondaq on Twitter
Register for Access and our Free Biweekly Alert for
This service is completely free. Access 250,000 archived articles from 100+ countries and get a personalised email twice a week covering developments (and yes, our lawyers like to think you’ve read our Disclaimer).
Email Address
Company Name
Confirm Password
Mondaq Topics -- Select your Interests
 Law Performance
 Law Practice
 Media & IT
 Real Estate
 Wealth Mgt
Asia Pacific
European Union
Latin America
Middle East
United States
Worldwide Updates
Registration (you must scroll down to set your data preferences)

Mondaq Ltd requires you to register and provide information that personally identifies you, including your content preferences, for three primary purposes (full details of Mondaq’s use of your personal data can be found in our Privacy and Cookies Notice):

  • To allow you to personalize the Mondaq websites you are visiting to show content ("Content") relevant to your interests.
  • To enable features such as password reminder, news alerts, email a colleague, and linking from Mondaq (and its affiliate sites) to your website.
  • To produce demographic feedback for our content providers ("Contributors") who contribute Content for free for your use.

Mondaq hopes that our registered users will support us in maintaining our free to view business model by consenting to our use of your personal data as described below.

Mondaq has a "free to view" business model. Our services are paid for by Contributors in exchange for Mondaq providing them with access to information about who accesses their content. Once personal data is transferred to our Contributors they become a data controller of this personal data. They use it to measure the response that their articles are receiving, as a form of market research. They may also use it to provide Mondaq users with information about their products and services.

Details of each Contributor to which your personal data will be transferred is clearly stated within the Content that you access. For full details of how this Contributor will use your personal data, you should review the Contributor’s own Privacy Notice.

Please indicate your preference below:

Yes, I am happy to support Mondaq in maintaining its free to view business model by agreeing to allow Mondaq to share my personal data with Contributors whose Content I access
No, I do not want Mondaq to share my personal data with Contributors

Also please let us know whether you are happy to receive communications promoting products and services offered by Mondaq:

Yes, I am happy to received promotional communications from Mondaq
No, please do not send me promotional communications from Mondaq
Terms & Conditions (the Website) is owned and managed by Mondaq Ltd (Mondaq). Mondaq grants you a non-exclusive, revocable licence to access the Website and associated services, such as the Mondaq News Alerts (Services), subject to and in consideration of your compliance with the following terms and conditions of use (Terms). Your use of the Website and/or Services constitutes your agreement to the Terms. Mondaq may terminate your use of the Website and Services if you are in breach of these Terms or if Mondaq decides to terminate the licence granted hereunder for any reason whatsoever.

Use of

To Use you must be: eighteen (18) years old or over; legally capable of entering into binding contracts; and not in any way prohibited by the applicable law to enter into these Terms in the jurisdiction which you are currently located.

You may use the Website as an unregistered user, however, you are required to register as a user if you wish to read the full text of the Content or to receive the Services.

You may not modify, publish, transmit, transfer or sell, reproduce, create derivative works from, distribute, perform, link, display, or in any way exploit any of the Content, in whole or in part, except as expressly permitted in these Terms or with the prior written consent of Mondaq. You may not use electronic or other means to extract details or information from the Content. Nor shall you extract information about users or Contributors in order to offer them any services or products.

In your use of the Website and/or Services you shall: comply with all applicable laws, regulations, directives and legislations which apply to your Use of the Website and/or Services in whatever country you are physically located including without limitation any and all consumer law, export control laws and regulations; provide to us true, correct and accurate information and promptly inform us in the event that any information that you have provided to us changes or becomes inaccurate; notify Mondaq immediately of any circumstances where you have reason to believe that any Intellectual Property Rights or any other rights of any third party may have been infringed; co-operate with reasonable security or other checks or requests for information made by Mondaq from time to time; and at all times be fully liable for the breach of any of these Terms by a third party using your login details to access the Website and/or Services

however, you shall not: do anything likely to impair, interfere with or damage or cause harm or distress to any persons, or the network; do anything that will infringe any Intellectual Property Rights or other rights of Mondaq or any third party; or use the Website, Services and/or Content otherwise than in accordance with these Terms; use any trade marks or service marks of Mondaq or the Contributors, or do anything which may be seen to take unfair advantage of the reputation and goodwill of Mondaq or the Contributors, or the Website, Services and/or Content.

Mondaq reserves the right, in its sole discretion, to take any action that it deems necessary and appropriate in the event it considers that there is a breach or threatened breach of the Terms.

Mondaq’s Rights and Obligations

Unless otherwise expressly set out to the contrary, nothing in these Terms shall serve to transfer from Mondaq to you, any Intellectual Property Rights owned by and/or licensed to Mondaq and all rights, title and interest in and to such Intellectual Property Rights will remain exclusively with Mondaq and/or its licensors.

Mondaq shall use its reasonable endeavours to make the Website and Services available to you at all times, but we cannot guarantee an uninterrupted and fault free service.

Mondaq reserves the right to make changes to the services and/or the Website or part thereof, from time to time, and we may add, remove, modify and/or vary any elements of features and functionalities of the Website or the services.

Mondaq also reserves the right from time to time to monitor your Use of the Website and/or services.


The Content is general information only. It is not intended to constitute legal advice or seek to be the complete and comprehensive statement of the law, nor is it intended to address your specific requirements or provide advice on which reliance should be placed. Mondaq and/or its Contributors and other suppliers make no representations about the suitability of the information contained in the Content for any purpose. All Content provided "as is" without warranty of any kind. Mondaq and/or its Contributors and other suppliers hereby exclude and disclaim all representations, warranties or guarantees with regard to the Content, including all implied warranties and conditions of merchantability, fitness for a particular purpose, title and non-infringement. To the maximum extent permitted by law, Mondaq expressly excludes all representations, warranties, obligations, and liabilities arising out of or in connection with all Content. In no event shall Mondaq and/or its respective suppliers be liable for any special, indirect or consequential damages or any damages whatsoever resulting from loss of use, data or profits, whether in an action of contract, negligence or other tortious action, arising out of or in connection with the use of the Content or performance of Mondaq’s Services.


Mondaq may alter or amend these Terms by amending them on the Website. By continuing to Use the Services and/or the Website after such amendment, you will be deemed to have accepted any amendment to these Terms.

These Terms shall be governed by and construed in accordance with the laws of England and Wales and you irrevocably submit to the exclusive jurisdiction of the courts of England and Wales to settle any dispute which may arise out of or in connection with these Terms. If you live outside the United Kingdom, English law shall apply only to the extent that English law shall not deprive you of any legal protection accorded in accordance with the law of the place where you are habitually resident ("Local Law"). In the event English law deprives you of any legal protection which is accorded to you under Local Law, then these terms shall be governed by Local Law and any dispute or claim arising out of or in connection with these Terms shall be subject to the non-exclusive jurisdiction of the courts where you are habitually resident.

You may print and keep a copy of these Terms, which form the entire agreement between you and Mondaq and supersede any other communications or advertising in respect of the Service and/or the Website.

No delay in exercising or non-exercise by you and/or Mondaq of any of its rights under or in connection with these Terms shall operate as a waiver or release of each of your or Mondaq’s right. Rather, any such waiver or release must be specifically granted in writing signed by the party granting it.

If any part of these Terms is held unenforceable, that part shall be enforced to the maximum extent permissible so as to give effect to the intent of the parties, and the Terms shall continue in full force and effect.

Mondaq shall not incur any liability to you on account of any loss or damage resulting from any delay or failure to perform all or any part of these Terms if such delay or failure is caused, in whole or in part, by events, occurrences, or causes beyond the control of Mondaq. Such events, occurrences or causes will include, without limitation, acts of God, strikes, lockouts, server and network failure, riots, acts of war, earthquakes, fire and explosions.

By clicking Register you state you have read and agree to our Terms and Conditions