PATENT REEXAMINATION BOARD OF THE STATE INTELLECTUAL PROPERTY OFFICE OF THE PEOPLE S REPUBLIC OF CHINA EXAMINATION DECISION OF INVALIDATION REQUEST Decision No. 9817 Decision Date April 29, 2007 Title of Invention-Creation Novel Inhalable Powder Containing Tiotropium IPC A61K9/00 A61K31/46 A61P11/00 A61P11/06 Requester for Invalidation JIANGSU CHIA TAI TIANQING PHARMACEUTICAL CO., LTD. Respondent Patent No. 01803098.X Application Date September 28, 2001 Grant Publication Date Head of the Panel LI Renjiu Primary Examiner XU Lei Participant Examiner HE Wei Drawings Legal Basis Article 22, paragraph 3, Article 26, paragraph 3 and Article 26, paragraph 4 of the Patent Law, Rule 20, paragraph 1 and Rule 21, paragraph 2 of the Implementing Regulations of the Patent Law Key Points of the Decision: An invention is obvious and does not have prominent substantive features if the person skilled in the art would be able to reach the invention only through logical analysis, reasoning or limited experiments on the basis of the prior art. I. Cause of Actions The request for invalidation relates to the invention patent No. 01803098.X (hereinafter referred to as the patent), filed on September 28, 2001, entitled Novel Inhalable Powder Containing Tiotropium and granted by the State Intellectual Property Office on July 13, 2005, with the priority date of October 12, 2000 and the patentee of BOEHRINGER INGELHEIM PHARMA GMBH & CO KG. The claims of the granted patent are as follows: Disclaimer: This translation is provided by a third party service, and IP Key does not guarantee the accuracy of the translated pages. In case of a discrepancy, the original Chinese document shall prevail.
1. An inhalable powder comprising 0.04-0.8% of tiotropium in admixture with a physiologically acceptable excipient, characterized in that the excipient consists of a mixture of excipient with an average particle size of 15-80 μm and excipient with an average particle size of 1-9 μm, the proportion of the excipient with an average particle size of 1-9 μm constituting 1-20% of the total amount of excipients, and the tiotropium salt used has an average particle size of 0.5-10 μm. 2. The inhalable powder of claim 1, characterized in that tiotropium is present in the form of chloride, bromide, iodide, methanesulphonate, para-toluenesulphonate or methyl sulfate thereof. 3. The inhalable powder of claim 1 or 2, characterized by comprising between 0.048% and 0.96% of tiotropium bromide. 4. The inhalable powder of claim 1 or 2, characterized by comprising between 0.05% and 1% of tiotropium bromide monohydrate. 5. The inhalable powder of claim 3, characterized by comprising between 0.05% and 1% of tiotropium bromide monohydrate. 6. The inhalable powder of claim 1 or 2, characterized in that the excipient mixture consists of excipient with an average particle size of 17-50 μm and excipient with an average particle size of 2-8 μm. 7. The inhalable powder of claim 3, characterized in that the excipient mixture consists of excipient with an average particle size of 17-50 μm and excipient with an average particle size of 2-8 μm. 8. The inhalable powder of claim 4, characterized in that the excipient mixture consists of excipient with an average particle size of 17-50 μm and excipient with an average particle size of 2-8 μm. 9. The inhalable powder of claim 5, characterized in that the excipient mixture consists
of excipient with an average particle size of 17-50 μm and excipient with an average particle size of 2-8 μm. 10. The inhalable powder of claim 1 or 2, characterized in that the proportion of the excipient with an average particle size of 1-9 μm in the total amount of excipient is 3-15%. 11. The inhalable powder of claim 3, characterized in that the proportion of the excipient with an average particle size of 1-9 μm in the total amount of excipient is 3-15%. 12. The inhalable powder of claim 4, characterized in that the proportion of the excipient with an average particle size of 1-9 μm in the total amount of excipient is 3-15%. 13. The inhalable powder of claim 5, characterized in that the proportion of the excipient with an average particle size of 1-9 μm in the total amount of excipient is 3-15%. 14. The inhalable powder of claim 6, characterized in that the proportion of the excipient with an average particle size of 2-8 μm in the total amount of excipient is 3-15%. 15. The inhalable powder of claim 1 or 2, characterized in that the excipient includes monosaccharide, disaccharide, oligo- and polysaccharide, polyalcohol, salt, or mixtures thereof which are used as the excipients. 16. The inhalable powder of claim 15, characterized in that the excipient includes glucose, arabinose, lactose, saccharose, maltose, dextrane, sorbitol, mannitol, xylitol, sodium chloride, calcium carbonate or mixtures thereof which are used as the excipients. 17. The inhalable powder of claim 16, characterized in that the excipient include glucose or lactose or mixtures thereof which are used as the excipient.
18. A use of the inhalable powder of claim 1 or 2 in the preparation of a pharmaceutical composition for treating asthma or COPD. 19. A use of the inhalable powder of claim 1 or 2 in the preparation of a capsule. 20. A capsule, characterized by comprising 3-10 mg of inhalable powder of claim 1 or 2. 21. The capsule of claim 19, characterized by comprising between 1.2 μg and 80 μg of tiotropium. JIANGSU CHIA TAI TIANQING PHARMACEUTICAL CO., LTD. (hereinafter referred to as the petitioner) filed a request for invalidation against the patent on August 31, 2006 with the Patent Reexamination Board. The petitioner asserted that: (1) claims 3-5, 15-17 and 21 of the patent do not conform to the provision of Rule 20, paragraph 1 of the Implementing Regulations of the Patent Law; (2) claims 1-21 do not conform to the provisions of Article 22, paragraph 3, Article 26, paragraph 4 of the Patent Law and Rule 21, paragraph 2 of the Implementing Regulations of the Patent Law; and (3) the specification does not conform to the provision of Article 26, paragraph 3 of the Patent Law. The following annexes were submitted: Annex 1: US patent No. 5,478,578A, published on December 26, 1995, total of 3 pages; Annex 2: Tiotropium bromide, a new long-acting antimuscarinic bronchodilator: a pharmacodynamic study in patients with chronic obstructive pulmonary disease (COPD), F. P. V. Maesen et al., Eur Respir J, August 1995, pages 1506-1513, total of 8 pages; The petitioner held the following opinions in the request for invalidation: (1) The wording comprising between and of tiotropium (bromide monohydrate) in claims 3-5 and 21 renders unclear protection scopes. The expression the excipient includes or mixtures thereof which are used as the excipients in
claims 15-17 renders unclear protection scopes as what it refers to is unclear. Claim 21 incorrectly refers to claim 19 by the wording the capsule of claim 19, and renders an unclear protection scope. Therefore, claims 3-5, 15-17 and 21 do not conform to the provision of Rule 20, paragraph 1 of the Implementing Regulations of the Patent Law. (2) The objective of the present invention is to provide a tiotropium powdery preparation capable of being accurately weighted and having good emptying performance. However, the requirement for high uniformity of powder cannot be achieved by randomly mixing any two excipients having different average particle sizes defined in claim 1. Therefore, claim 1 lacks essential technical features. Claims 18, 19 and 21 fail to respectively further define how to make the inhalable powder of claim 1 or 2 into a pharmaceutical composition and capsule which is capable of achieving the objective of the patent. Claim 20 does not further define how to process the powder to make it highly uniform. Claims 2-17 directly or indirectly refer to claim 1. Therefore, claims 1-21 do not conform to the provision of Rule 21, paragraph 2 of the Implementing Regulations of the Patent Law. (3) Claim 1 does not define the excipients applicable to the present invention, and claim 1 comprises numerous variants each of which is variable within a broad range. Therefore, claim 1 does not conform to the provision of Article 26, paragraph 4 of the Patent Law. Claims 2-21 still do not limit the scope of claim 1 to the extent that could be reasonably speculated as implementable by the person skilled in the art. Therefore, claims 2-21 1 do not conform to the provision of Article 26, paragraph 4 of the Patent Law either. (4) The technical problem to be solved by Annex 1 is the same as in the present invention. The only difference between Annex 1 and claim 1 of the present invention is that Annex 1 does not indicate the specific active component. Other features of claim 1, such as those relating to components, particle sizes and amount (see column 1, lines 44-61, column 2, line 31, table 1, and table 2 of the specification and claim 1 of Annex 1) overlap with those in claim 1. In Example 2 of Annex 1, in particular, features other than the active component, such as those relating to components, particle sizes and 1 Note from translators: the decision has a typo here. According to the context, it should be claims 1-21.
amount completely fall within the scope covered by claim 1. Annex 2 discloses that tiotropium bromine, as an active substance, can be made into an inhalable powder for treating COPD with a single dose of 10-80 μg (10, 20, 40 and 80 μg). Annex 2 further discloses that tiotropium bromine is structurally related to ipratropium bromide (see the last paragraph on page 1506 of Annex 2). The person skilled in the art can directly derive the technical solution of claim 1 from the disclosure of Annex 1 in combination with the disclosure of Annex 2, therefore, claim 1 does not conform to the provision of Article 22, paragraph 3 of the Patent Law of China in view of the combination of Annexes 1 and 2. Annex 2 discloses the additional technical feature of claim 2. Example 2 of Annex 1 discloses the additional technical features of claims 3-14 and 21. Annex 1 discloses the additional technical features of claims 15-17 in lines 24-29 in column 2 of the description thereof, and therefore, the solutions of claims 2-17 and 21 do not involve an inventive step over Annexes 1 and 2 either. As the inhalable powder of claim 1 or 2 is obvious in view of Annexes 1 and 2, claims 18-20 do not involve an inventive step either. (5) The specification fails to provide: the specific particle size of the active component in the examples; what accurate weighing performance does the obtained product have; how the amount of the mixture and the amount of tiotropium bromide monohydrate vary slightly between various batches; how the powder has good emptying performance; and how to make it possible to administer the active substance in a high absorption ratio. Therefore, the person skilled in the art could not know whether the product made has the expected effect in the patent. Second, the claims of the patent comprise numerous variants each of which is variable within a broad range. However, since the specification only describes lactose monohydrate and two particle sizes used in the example and does not specifically describe examples of other excipients nor describes excipients having other particle sizes, the person skilled in the art could not determine that the invention and said effect can be achieved within the scope defined by the claims. Therefore, the specification does not conform to the provision of Article 26, paragraph 3 of the Patent Law. The petitioner submitted Chinese translations of the full text of Annexes 1 and 2 and an original copy of notarial deed for notarizing Annex 2 in a supplementary manner on September 27, 2006.
After the formality examination was passed, the Patent Reexamination Board ( PRB ) accepted the request and issued Acceptance Notice of Invalidation Request to the two parties on November 1, 2006. PRB forwarded the Request for Invalidation and a copy of documents listed in the Annex List thereof and a copy of documents submitted by the petitioner on September 27, 2006 to the patentee, requiring the patentee to make a response within a specified time limit, and at the same time a panel for examination of the case was set up. The patentee submitted Observations on December 18, 2006, asserting that: (1) The wording between and in claims 3-5 and 21 define the range of content of substances such as tiotropium ; the expression the excipient includes or mixtures thereof which are used as the excipients in claims 15-17 defines the excipient as used. Claim 21 is an independent product claim. It is clear regardless of its reference to claim 19. Therefore, claims 3-5, 15-17 and 21 all conform to the provision of Rule 20, paragraph 1 of the Implementing Regulations of the Patent Law. (2) The patent does not invent a novel excipient, so it is not necessary to define the types of the excipient as an essential technical feature in the independent claim 1, and claims 1-21 also do not lack essential technical features. (3) The specification describes the composition of the inhalable powder of the patent, a preparation method thereof, and illustrates how to obtain an excipient mixture, the final inhalable powder and the preparation of capsule by using the same. It also describes the particle size of active substance and how to determine whether tiotropium is within such a particle size range. It further discloses a method for preparing tiotropium bromine monohydrate having a desired particle size in the preparation of tiotropium bromine monohydrate and lists a large number of excipients that can be used for the patent in the description. Therefore, claims 1-21 are well supported by the description, conforming to the provision of Article 26, paragraph 4 of the Patent Law. (4) Annex 2, as an overview, does not involve formulation technology and does not contain any content concerning the improvement of formulation of tiotropium bromine,
and is completely irrelevant to the patent. The amount of the inhalable portion of the active component of the inhalable powder in Annex 1 depends on the amount of the finer excipient. According to Annex 1, especially Examples 1 and 2 thereof, the inhalable portion of the active component increases with the increase of the amount of the finer excipient. However, in the present invention, as shown in Figs. 1-3, although the inhalable portion increases with the addition of the finer excipient, the deviation of the inhalable portion is very low when 5% of the finer excipient is added, and the deviation of the inhalable portion when 10% of the finer excipient is added is higher than that of powder containing 5% of the finer excipient. Therefore, the person skilled in the art would not expect according to Annex 1 that the deviation of the inhalable portion is within an acceptable range only when the amount of the finer excipient is defined. Moreover, Annex 1 does not mention the active substance tiotropium of the present patent anywhere. Thus, according to Annexes 1 and 2, the person skilled in the art would not expect that the amount of the finer excipient not only determines the inhalable portion of tiotropium but also plays an important role in deviations of the inhalable portion among batches. Therefore, claims 1-21 involve an inventive step. (5) The administration of tiotropium for treating respiratory diseases is known in the art. Since the specification of the patent has already described the composition and preparation method of the inhalable powder, processing of the active substance, the excipients for use, and the using methods of the inhalable powder and capsule in detail and given specific examples to explain how to obtain the excipient mixture and the final inhalable powder and prepare the capsule by using the inhalable powder, the person skilled in the art can reproduce the inhalable powder of the patent according to the illustration of the specification. Therefore, the description of the patent conforms to the provision of Article 26, paragraph 3 of the Patent Law. The patentee submitted Counterevidence 1 at the same time: Counterevidence 1: relevant content and translation of response opinions submitted by the patentee to the European Patent Office on July 25, 2003, 10 pages in total. The panel issued Oral Hearing Notice of Invalidation Request to two parties concerned on February 6, 2007, setting oral hearing on March 21, 2007. Together with the Notice,
the panel forwarded the Observations and Counterevidence 1 submitted by the patentee to the petitioner and forwarded a copy of notarial deed for notarizing Annex 2 submitted by the petitioner on September 27, 2006 to the patentee. Both parties concerned and agents thereof attended the oral hearing which was held on March 21, 2007 as scheduled. During oral hearing, the two parties concerned had no objection to identities and qualification of the persons attending the hearing from the opposite party and made no challenge against any member of the panel. The petitioner and the patentee both expressed that they had received relevant documents forwarded by the panel. The patentee had no objection to the authenticity and public availability of all the Annexes submitted by the petitioner, but asserted that numeral 6 in the middle of the last line of column 2 in the table of Example 1 on page 4 of the Chinese translation of Annex 1 should be 16, and the expression compared with experiment day 1 in line 2 below table 4 on page 8 of the Chinese translation of Annex 2 should be compared with placebo control, and had no objection to other translations. The petitioner admitted that the above two translations were incorrect, and accepted the two translations as corrected by the patentee. The petitioner had no objection to the authenticity of Counterevidence 1 submitted by the patentee. The panel investigated the invalidation grounds and evidences involved in the case, and the two parties concerned sufficiently stated their opinions. Besides the opinions stated in the Request for Invalidation of Patent Rigtht, the petitioner also asserted that claims 1-21 lack essential technical features due to lack of description on the flow property of the excipient and thus do not conform to Rule 21, paragraph 2 of the Implementing Regulations of the Patent Law, and due to an unclear concept average particle size used in the description, the description cannot be implemented and thus does not conform to Article 26, paragraph 3 of the Patent Law. The patentee asserted that the new assertions proposed by the petitioner during the oral hearing, regarding Article 26, paragraph 3 of the Patent Law and Rule 21, paragraph 2 of the Implementing Regulations of the Patent Law, are new grounds proposed one month after the invalidation request was proposed and thus should not be considered. The patentee s other opinions are the same as those in its Observations. The panel notified the two parties during the hearing that the new assertions proposed by the
petitioner, regarding Article 26, paragraph 3 of the Patent Law and Rule 21, paragraph 2 of the Implementing Regulations of the Patent Law, exceeded the time limit for presenting evidences, and thus are not in conformity with the provision of Rule 66 of the Implementing Regulations of the Patent Law. Therefore, the new assertions will not be considered. The patentee submitted an original copy of notarial deed (18 pages in total) for proving the authenticity of contents of Counterevidence 1 after the end of the oral hearing. The patentee and the petitioner respectively submitted Observations summarising the opinions in oral hearing on March 26, 2007. Now, the panel believes that facts involved in the case are clear, and an examination decision can be made. II. Reasons for the Decision 1. Grounds and evidences for invalidation According to the statements of the two parties in written opinions and during oral hearing, the invalidation grounds heard by the panel are as follows: (1) claims 3-5, 15-17 and 21 do not conform to the provision of Rule 20, paragraph 1 of the Implementing Regulations of the Patent Law; (2) claims 1-21 do not conform to the provisions of Article 22, paragraph 3 and Article 26, paragraph 4 of the Patent Law and Rule 21, paragraph 2 of the Implementing Regulations of the Patent Law; and (3) the specification does not conform to the provision of Article 26, paragraph 3 of the Patent Law. The petitioner had no objection to the authenticity and publicity of Annexes 1 and 2, which were published prior to the filing date of the patent and could be used as the prior art for evaluating the inventiveness of the patent. The patentee and the petitioner agreed with the accuracy of translations of Annexes 1 and 2. The original translations submitted by the petitioner shall prevail except for the parts modified during the hearing.
2. Rule 20, paragraph 1 of the Implementing Regulations of the Patent Law According to Rule 20, paragraph 1 of the Implementing Regulations of the Patent Law, the claims of a patent shall state the technical features of the invention or utility model therein, and clearly and concisely define the scope of protection sought by the patent. Terms used in claims should generally be understood with meanings they usually have in the relevant technical field. In this case, the petitioner asserted that the wording between and in claims 3-5 and the expression the excipient includes or mixtures thereof which are used as the excipients in claims 15-17 render these claims unclear; claim 21 is a product claim, and the subject matter of claim 19 is a use, so claim 21 referring to claim 19 renders an unclear reference relationship. To this point, the panel held that when defining the content of the active component, the expression comprising between and in claims 3-5 obviously has the meaning generally understood by the person skilled in the art; for example, the expression comprising between 1.2 μg and 80 μg of tiotropium should be understood as comprising from 1.2 μg to 80 μg of tiotropium ; that is, the expression comprising between and is obviously equivalent to the expression comprising from to, and has no ambiguity as to be understood otherwise. Claims 15-17 refer to other claims which relate to powders including coarser and finer excipients. However, it has already been clearly pointed out in line 18 on page 3 of the specification of the patent that coarser and finer excipients may consist of chemically identical or chemically different substances. Therefore, the first ''excipient" in the expression the excipient includes or mixtures thereof which are used as the excipients apparently may be coarser particles or finer particles, which will not render the claim unclear. Following the first ''excipient", selectable types of the excipient are listed. The second ''excipient" apparently refers to the types of the excipient listed previously, and is not ambiguous either. Therefore, claims 3-5 and claims 15-17 can be clearly understood according to the general meanings in the relevant technical field, and have clear protection scopes.
It can be seen from the expression the capsule of claim 19 in the preamble portion of claim 21 that claim 21 clearly shows that the subject matter sought for protection thereby is a product, which is the product claimed by claim 19. Claim 19 reads a use of the inhalable powder of claim 1 or 2 in the preparation of a capsule. Although the subject matter of claim 19 is a use, a capsule is made obviously according to such a use. That is, claim 19 is related to the capsule. Therefore, the capsule of claim 21 is apparently the one that is made according to the use of claim 19, and thus claim 21 is also clear. In conclusion, the expressions of claims 3-5, 15-17 and 21 are all clear, conforming to the provision of Rule 20, paragraph 1 of the Implementing Regulations of the Patent Law. 3. Article 22, paragraph 3 of the Patent Law Article 22, paragraph 3 of the Patent Law provides that: inventiveness means that, as compared with the prior art before the application date, the invention has prominent substantive features and represents a notable progress, and that the utility model has substantive features and represents a progress. According to the provision of this paragraph, an invention is obvious and does not have prominent substantive features if the invention can be obtained by a person in the relevant art only through logical analysis, reasoning or limited experiments on the basis of the prior art. In this case, claim 1 seeks to protect an inhalable powder containing tiotropium, and Annex 1 discloses an inhalable powder for drugs with high activity, consisting of carriers having specific proportions of finer particles and coarser particles. The technical problems to be solved by Annex 1 are the same as those in the patent, i.e., both for improving the properties of the inhalable powder, optimising or controlling the inhalable active substance content of the powder so as to achieve a high accuracy of metering (see paragraphs 1-6 on page 2 of the translation of Annex 1). The technical means for solving the technical problems in Annex 1 is also using a mixed powder consisting of finer and coarser particle excipients. Example 1 of Annex 1 discloses a
capsule for inhalation of a highly active drug fenoterol with a fine particle size (0.1 mg per capsule, with an average particle size of less than 6 μm). The capsule contains glucose having both coarser particles with a particle size of 35 μm and finer particles with a particle size of 5 μm. It provides two solutions where the contents of fine particles are 4% and 16% respectively. Example 2 of Annex 1 discloses a capsule for inhalation of a highly active drug ipratropium bromide with a fine particle size (0.04 mg per capsule, with an average particle size of less than 6 μm). The capsule contains glucose having both coarser particles with a particle size of 35 μm and finer particles with a particle size of 8 μm. It provides two solutions where the contents of fine particles are 5% and 10% respectively. Annex 1 also points that, with respect to the active component administered by inhalation, 0.01 to 0.1 mg of active substance corresponds to about 5 mg of excipient (i.e., the content of the active component is 0.2-2%) (see lines 2-4 on page 3 of translation of Annex 1). The contents of the active substance in the two examples are equivalent to 2wt% and 0.8wt% respectively. Thus Annex 1 discloses a majority of technical features of claim 1, and differs from claim 1 only in that the active component used in the solution of Annex 1 is different from that of claim 1. That is, Annex 1 does not mention that the active component is tiotropium bromine, but it teaches that the powder is used for administrating highly active drug by inhalation and it provides the specific example of ipratropium bromide as well. Annex 2, as a prior art of the patent, shows that tiotropium bromine is structurally related to ipratropium bromide. It also provides a description on the dose and pharmacological activity of tiotropium bromine, and points out that tiotropium bromine and ipratropium bromide have comparable effects (see abstract, lines 3-4 on page 2 and lines 2-3 on page 10 of translation of Annex 2). Therefore, based on the fact that Annex 1 teaches using coarser and finer particle excipients to achieve a powder which can be metered with a high accuracy and provides a specific technical solution where ipratropium bromide is used as an active substance in the inhalable powder, and where all features in the solution except the active substance fall within the protection scope of the patent, the person skilled in the art would obtain the technical solution sought for protection by claim 1 in conjunction with the teachings given by the prior art, i.e., Annex 2, that tiotropium bromine is structurally related to ipratropium bromide and can be used as inhalable drug with high activity, through logical analysis, reasoning or limited experiments and without any creative effort being made. Moreover, as Annex 1 discloses that the inhalable powder with good metering property can be obtained when
the content of the fine excipient is 4%, 5%, 16% or 10%, the solution of the present invention does not produce any unexpected effect. Therefore, claim 1 does not have prominent substantive features and does not involve an inventive step under Article 22, paragraph 3 of the Patent Law. The patentee contends that Annex 1 teaches that the amount of the inhalable portion of the inhalable powder increases with the increase of the fine excipient. As indicated by Counterevidence 1, it is found in the present invention that the increase of the fine excipient is not always favourable. Therefore, Annex 1 does not teach limiting the amount of the fine excipient within a certain range. Further, Annex 1 does not mention the active substance of the patent, and Annex 2 does not relate to a formulation technology. Therefore, the combination of Annexes 1 and 2 cannot destroy the inventive step of the claim. To this point, the panel s opinions are as follows. Firstly, the objectives of Annex 1 and the present invention are the same - providing an inhalable powder which can optimise or control the inhalable amount of an active component and which has excellent flow property, dispersity and emptying property. It is well known to the person skilled in the art that many problems such as those concerning dust and flow property occur when there are too many fine particles. Also it is clearly pointed out in Annex 1 that excipient, with its relatively high proportion in the powder, essentially determines the properties of the powder, generally speaking, the finer the powder, the poorer its flow properties, good flow properties are the prerequisite for a high accuracy of metering when filling individual containers with a predetermined dose, so the excipient used must not be too fine (see lines 12-15 on page 2 of translation of Annex 1). Therefore, the person skilled in the art, when considering various factors, would not reach a conclusion from Annex 1 as asserted by the patentee that the increase of the fine excipient is always favourable for the powder. Moreover, Examples 1 and 2 of Annex 1 indicates that when the amount of the fine particle excipient increases from 0 to 10% or 25% for example, the proportion of the inhalable component increases obviously, from 15.1% to 23.0% and 33.4% respectively. While the content of fine particles increases from 25% to 50%, the proportion of the inhalable component increases only from 33.4% to 38.8%. That is, the increase slows down obviously. Therefore one would not reach that Annex 1 teaches that the increase of the fine excipient is always
favourable. In addition, according to teachings of Annex 1, the weight ratio of finer and coarser particle excipients is between 1:99 and 95:5, preferably between 5:95 and 70:30, and more preferably between 10:90 and 50:50. From the hierarchy of preference, one would not conclude as what is asserted by the patentee that the inhalable portion of the active component increases with the increase of the amount of the fine excipient. Therefore, in view of the above, the assertion of the patentee that Annex 1 teaches the increase of fine excipient is always favourable for the powder and the inhalable portion of the active component increases with the increase of the amount of the fine excipient is untenable. Secondly, according to the description of the specification of the patent, the content of the fine excipient particles in the inhalable powder for achieving the objective of the invention may be from 1-20%, preferably 3-15%, and most preferably 5-10% (see claims 1 and 11-14, and lines 25-27 on page 2 and lines 12-13 on page 3 of the description of the patent). The specification neither says that a content of 5% of fine excipient is better than a content of 10% of fine excipient, nor says that the objective of the invention cannot be achieved with values within the range of 1-20% other than 5%. In the solution of Example 3 of the patent, the content of the fine excipient particles is 10%. Therefore, even if the patentee believes that the deviation of the content of the inhalable active component between batches becomes larger when the content of the fine particle excipient is more than 5%, one could not reach the conclusion that the powder could not achieve the objective of the invention when the amount of the fine particle excipient is more than 5%. Thirdly, Annex 1 describes that the content ratio of finer and coarser particle excipients is preferably between 5:95 and 70:30, more preferably between 10:90 and 50:50 (that is, the content of fine particles accounts for 5-70% of the total amount of the excipient, preferably 10-50%). The ranges overlap with the numerical range of 1-20% sought for protection by claim 1 of the patent. Examples 1 and 2 of Annex 1 further provide several specific technical solutions in which the content of the fine particle excipient is 5%, 10% and the like, which fall within the scope sought for projection of claim 1 of the patent. The patentee did not prove that the solution of the patent has an unexpected effect compared with the solution of Annex 1. In summary, except for different active components, Annex 1 is the same as the patent in technical problems to be solved and technical means adopted. No evidence shows that the solution of the patent achieves an unexpected effect compared with the solution of Annex 1. The argument and the Counterevidence 1 provided by the patentee cannot prove that claim 1 has prominent
substantive features in view of the combination of Annexes 1 and 2 either. Therefore, claim 1 does not involve an inventive step under Article 22, paragraph 3 of the Patent Law. Claims 2-5 further define the active component - tiotropium bromine of claim 1 by its compound form and content respectively. As mentioned above, although Annex 1 does not mention tiotropium bromine, it teaches that the powder can be used for highly active components the content of which is about 0.2-2% as described therein. The person skilled in the art would expect that the technical solution of the patent could not generate an unexpected effect due to different compound presence forms of the active component. In the case where claim 1 does not involve an inventive step, it is a conventional choice of the person in the relevant art to select different compound presence forms of tiotropium bromine. Therefore, the person skilled in the art would obtain the solutions of claims 2-5 in combination with Annexes 1 and 2, obviously without creative effort, and thus these claims do not conform to the provision of Article 22, paragraph 3 of the Patent Law either. Claims 6-17 respectively define the particle size, content and type of the excipient, and these additional technical features are all disclosed by Annex 1 (page 2, paragraphs 6-7, page 3, paragraphs 1-2 and 5, and Examples 1 and 2 of translation of Annex 1). Therefore, when the claims they refer to do not involve an inventive step, claims 6-17 do not involve an inventive step either for the aforesaid reasons. Claim 18 seeks to protect the use of the powder of claim 1 or 2 in the preparation of a pharmaceutical composition for treating asthma or COPD. Annex 2 discloses that tiotropium may be used for treating asthma and COPD. Therefore, when the claim it refers to does not involve an inventive step, claim 18 does not involve an inventive step either. Claim 19 seeks to protect a use of the powder of claim 1 or claim 2 in the preparation of a capsule. Annex 1 provides an embodiment of preparing capsules by using powder. Therefore, when the claim it refers to does involve an inventive step, claim 19 does not involve an inventive step either.
Claim 20 seeks to protect a capsule, which comprises 3-10 mg of inhalable powder of claim 1 or 2. Annex 1 discloses in paragraph 3 from bottom on page 3 of the translation that the amount of the mixture in a capsule is 5mg. Therefore, when the claim 1 or 2 it refers to does not involve an inventive step, claim 20 does not involve an inventive step either. Claim 21 seeks to protect the capsule of claim 19 which contains 1.2-80 μg of tiotropium. As described above, Annex 1 states that a single dose of the pharmaceutical preparation contains 0.01-0.1 mg of active substance. The person skilled in the art could determine the amount of active components contained in each capsule according to actual needs; and the content of ipratropium bromide which is relevant to tiotropium bromide structurally and functionally in Annex 1 is 0.04 mg (equivalent to 40 μg). The person skilled in the art would be able to determine the dose of tiotropium bromide according to the teaching of Annex 1 and the actual needs without any creative effort. Therefore, claim 21 does not involve an inventive step either. In conclusion, none of claims 1-21 of the patent involves an inventive step under Article 22, paragraph 3 of the Patent Law. Since all the claims of the patent should be declared invalid as they do not involve inventive steps, other invalidation grounds are not addressed. Based on the above facts and reasons, the panel makes the following examination decision. III. Decision The invention patent No. 01803098.X is declared to be invalid. Any party who is not satisfied with the decision may, within three months from receipt of the decision, file a lawsuit with Beijing No. 1 Intermediate People's Court, in accordance with Article 46, paragraph 2 of the Patent Law. According to this paragraph, where a party files a lawsuit, the other party shall intervene in the lawsuit as a third party.