When "the method for treatment of diseases" takes the shell of "pharmaceutical use"
I. History of the pharmaceutical use claim
In the field of biomedical patents, a special protection subject matter is presented in the form of pharmaceutical use claim. It is discovered that certain substance already known can be used to prevent or treat new indications.
If such technical solution is drafted as “use of substance X for the treatment of disease Y”, it can not be granted a patent right since it falls in the case under Article 25.1(3) of the Patent Law. However, if the technical solution is drafted in the form of “use of substance X for the manufacture a medicament for the treatment of disease Y” (i.e. new pharmaceutical use), it belongs to the method for preparing a medicament, and becomes a subject matter that can be granted a patent right.
Briefly, the “method for the treatment of disease” is packaged as the “method for preparing a medicament” to obtain a patent protection in return. After years of practice, it has been widely accepted in China.
II. Problems caused by the transformation in form
With regard to technical solution of method claim, it shall be defined by method feature such as procedure (for example steps, conditions), substance and apparatus (cf. Guidelines for Patent Examination).
When the technical solution of pharmaceutical use is compared with the prior art, one will notice that the substance X is known, and the preparation process has no difference from that in the prior art; the only distinguishing technical feature lies in that the substance X is used for the treatment of the disease Y. Briefly, the “indications” of the medicament is taken as the distinguishing technical feature.
However, with regard to the technical solution of method claim, it is unlikely to take the “indications” as the method features (for example, procedure, substance and apparatus). Therefore, the following problems revealed:
- Does “indication” define the technical solution of method?
- If the answer is no, how does pharmaceutical use achieve the requirement for granting?
- If the answer is yes, what is the principle for the “indications” to define the pharmaceutical use?
When the “method for the treatment of disease” is converted to the “method for preparing a medicament”, the contribution which originally plays important role in the “method for the treatment of disease” seems to be incompatible with “method for preparing a medicament”.
III. Pharmaceutical feature? or administration feature?
In clinical practice, it is found that improving the dosage/administration frequency of active ingredient would provide a better therapeutic effect. Even such kind of invention is converted into pharmaceutical use, it is still rather difficult to be granted. The challenging task is to figure out whether “dosage” defines pharmaceutical use claim. The top issue lies in that whether such “dosage” defines the manufacture process or merely defines the course of administration. A detailed classification of “dosage” is needed, whether it is the “administration dosage” (i.e. administration feature), or it is the “unit dosage” (pharmaceutical feature) in the process of medicament preparation.
“Administration dosage” (also as “dosing dosage”) is the dosage that the subject “eats” or “injected with” during the treatment, such dosage does not define a “compound” or “pharmaceutical use”. However, “unit dosage” refers to the smallest unit of medicament formed in the manufacture process; “unit dosage” defines both product claim and pharmaceutical use claim.
When the technical solution of the invention relates to the improvement of dosage, the dosage should be carefully worded. From the aspect of drafting, the wording “unit dosage””, “pharmaceutical unit” and the like can be used to define the technical solution.
The author further discusses the following two specific cases:
(1) When the technical solution involves the improvement of the administration dosage:
Using CN101094680A and its divisional applications as examples, they relate to a viscosupplementation device (the preferable form is a syringe) comprising sodium hyaluronate. The viscosupplementation device is used to inject the sodium hyaluronate into the articular cavity to relieve the pain of knee joint. When compared with the prior art, the distinguishing technical feature of the technical solution is that the larger injected volume (preferably 6ml) of sodium hyaluronate; whereas it is 3ml sodium hyaluronate injected in the prior art.
It is a typical invention relates to dosage improvement. During substantive examination of CN101094680A, the original expression of the claim is “The use of a viscosupplement in the manufacture of a device for treating a knee joint of a subject… wherein a single intra-articular administration of 4 ml or more of the viscosupplement is used and the single administration of the viscosupplement is therapeutically effective for at least 4 months”. Apparently, the expression “single intra-articular administration” indicates that said dosage is “administration feature”, thus the examiner points out that it does not define the technical solution.
Therefore, the technical solution is later amended to “A viscosupplement device, comprises a syringe containing 6±2 ml of viscosupplement...”, such that the “unit dosage of 6±2 ml” defines the technical feature.
When facing the technical solution drawn to dosage improvement, the following drafting forms can be considered so as to make the dosage define the technical solution:
- drafted as pharmaceutical use “The use of substance X for the preparation of unit dosage of a medicament for the treatment of disease Y, wherein the unit dosage comprises certain amount of substance X” (c.f. CN102357098B). The “amount” herein cannot be drafted in the form of “mg/kg body weight” or “mg/day”, otherwise it still belongs to administration feature.
- alternatively, drafted as a method for preparation which is defined by operation steps, raw materials, conditions, parameters, and the like, such as “A method for preparing a unit dosage ... ” (c.f. CN102119023B).
- alternatively, drafted as a pharmaceutical composition, such as “A pharmaceutical unit dosage composition comprising ... mg of compound ” (c.f. CN1384746B).
(2) When the improvement of technical solution relates to the administration frequency
When the technical solution relates to the improvement of the administration frequency, how to convert the administration feature “frequency” to the pharmaceutical feature? The feasible practice strategies can be found in the following cases:
Using CN1829482A as an example, it relates to a method of treating withdrawal or abstinence syndrome in a drug dependent or opioid tolerant patient in need of such treatment, the method comprising the following steps:
a) administering to said patient a first buprenorphine-containing transdermal dosage form for a first dosing period that is no longer than about 5 days;
b) administering to said patient a second buprenorphine-containing transdermal dosage form for a second dosing period that is no longer than about 5 days, wherein the second dosage form comprises the same dosage or a greater dosage of buprenorphine than the first dosage form; and
c) administering to said patient a third buprenorphine-containing transdermal dosage form for a third dosing period for at least 2 days, wherein the third dosage form comprises a greater dosage of buprenorphine than the second dosage form.
Apparently, the technical solution relates to the improvement of the administration frequency. However, the application was finally granted as a kit (c.f. CN1829482B) which is shown as:
A Kit comprising four buprenorphine-containing transdermal dosage forms and the instruction for the use thereof, the kit being used for the treatment of ... in a patient in need, wherein the kit comprising:
a) a first transdermal dosage form..., wherein the first dosage form contains 5mg of buprenorphine;
b) a second transdermal dosage form..., wherein the second dosage form contains 10mg of buprenorphine;
c) a third transdermal dosage form..., wherein the third dosage form contains 20mg of buprenorphine; and
d) a fourth transdermal dosage form..., wherein the fourth dosage form contains 20mg of buprenorphine.
In other words, the administration feature “frequency” is converted into a group of “element” in the kits, and each element comprises “unit dosage”. Such form of modification is also used in CN101730530B and CN100408040C.
IV. The dilemma encountered by the pharmaceutical feature in the examination of inventive step
To this end, the author searched the reexamination cases and invalidation cases relating to the improvement of dosage and administration frequency during the years 2007 to 2017 (for example, the decision No. 118944, 119194, 119777 and 121235).
The author noticed that in those patent reexamination and invalidation cases, the technical solutions are not novel over prior art, since the administration feature does not define a pharmaceutical use. Even though the novelty requirement is met, the examiner will further challenge the causal link between the technical effects and the pharmaceutical feature. The examiner will point out that the technical effects are obtained due to “administration feature”, rather than “pharmaceutical feature”, and then deny the inventive step of the technical solution.
It can be seen that overcoming one problem leads to another. Due to the transformation of “method for treating diseases” into “methods for preparing medicament” (the transformation of “administration feature” into “pharmaceutical feature”), the direct logic link between technical features and technical effects is separated.
Under current practice, how to help the inventors to obtain the deserved rights? the author proposes the following exploratory attempts:
(1) The author notices that the examiner usually points out that the medical workers can determine the administration dosage and frequency according to the patients’ condition, without paying any creative works.
With respect to this aspect, the author believes that the examiner violates the examination rules when he/she mentions “medical workers” (“physicians” or “doctors” and the like), since “medical workers” is not equivalent to “skilled persons in the art”, the examiner confuses these two concepts. The inventive step should be evaluated based on the knowledge and ability of skilled persons in the art, rather than physicians.
Furthermore, even the skilled persons in the art can adjust the administration dosage and the frequency in accordance with the patient’s weight, health conditions, such adjustment cannot go beyond the expected technical effect. Thus, it should pay attention particularly to whether the improved dosage or frequency confers new technical effect in the description. If the new technical effect cannot be expected by those skilled persons in the art, the improved administration feature (administration dosage and frequency) are not obvious.
(2) Next, it is necessary to reconnect the “pharmaceutical feature” to the technical effect.
In order to implement the improved “administration feature”, a specific matched “pharmaceutical feature” is needed. If the technical effect achieved by the “administration feature” is not obvious, those skilled in the art would have no motivation to prepare a medicament/device having particular “pharmaceutical feature” to match the “administration feature”.