Second medical use claims - current developments and challenges in - - PowerPoint PPT Presentation

Second medical use claims - current developments and challenges in Europe

Ahmedabad, January 15, 2019

• Dr. Markus Engelhard

German and European Patent Attorney München engelhard@boehmert.de

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Pharma Patents - Lifecycle

5 10 15 20 30 25 40 35 Assay / Screening process Compound class Composition / formulation New salts / new delivery / new matrices New indications New combinations

• f drugs

2010 New patient group Specific compound / drug candidate

5 years SPC 5 years SPC 3 years

New dosage regimen

Market authorization for product X

• r
• r

• 1. Second medical use claims

Use of compound X (for the manufacture of a medicament) for the treatment of disease y

(G005/83, G006/83, EPC 2000)

Compound X for use in a method of treatment of disease y

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• 1. Second Medical Use Claims

A fair balance must be struck between:

• 1. The (heavily) investing innovators

versus access to affordable medicines for the public

• 2. Incentives for innovators‘ R&D activities

versus prevention of patent protection being misused as „evergreening“ instrument

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• 1. Second Medical Use Claims

Patentability

New therapeutic applications can be based

• n (EPO practice):

1. A new indication 2. A new patient group to be treated 3. A different mode of drug administration 4. A different technical effect 5. A different dosage regimen

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• 1. Second Medical Use Claims

Patentability

Claim 1 of EP 0903148: „Use of ribavirin for the manufacture of a pharmaceutical composition for treating a patient having chronic hepatitis C infection to eradicate detectable HCV-RNA by a method comprising administering an effective amount of ribavirin in association with an effective amount of interferon alpha for a time period of 40 - 50 weeks, wherein the patient is

• ne having failed to respond to a previous course of

interferon alpha therapy, characterised in that the patient has a viral load of greater than 2 million copies per ml of serum as measured by HCV-RNA quantitative PCR of a HCV genotype 1 infection.“

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• 1. Second Medical Use Claims

Patentability

Selection of new patient group can confer novelty if: New patient group does not overlap with prior art patients (T893/90, T233/96, T531/04) New patient group is distinguished from known patients by physiological or pathological status (T19/86, T893/90, T1399/04, T734/12) New patient group has not been selected arbitrarily (T34/14)

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• 1. Second Medical Use Claims

Patentability

T734/12

"1. Use of an unconjugated antibody which is rituximab in the manufacture of a medicament for treating rheumatoid arthritis by intravenous administration of two doses of antibody of 1000 mg to a human who experiences an inadequate response to a TNFα-inhibitor, wherein the first dose is administered on day 1 of treatment and the second dose on day 15."

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• 1. Second Medical Use Claims

Patentability

T734/12 continued

Patentee: „The disclosure of document (10) was not detrimental to the novelty of the subject-matter of claims 1 and 2 of all claim requests since it disclosed neither a RA patient sub-group experiencing an inadequate response to a TNFα-inhibitor nor the successful treatment

• f this particular patient group.“

„… the RA patient group of claims 1 and 2 of the main request is distinguishable from the patient group of document (10) by its physiological and pathological status and consequently, according to the established case law of the Boards of Appeal (cf. Decisions T 1399/04, T 19/86 and T 893/90, above) represents a new therapeutic application.”

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• 1. Second Medical Use Claims

Patentability

T734/12 continued

Novelty by Selection Doctrine or by Inherency doctrine?

• G 2/88 (OJ 1990, 93, Corr. 469) emphasized that “the question to

be decided is was what has been “made available” to the public: the questions is not what might have been “inherent” in what was made available” to the public. Furthermore, when considering how far the teaching in a written description also made the inevitable result of carrying out such teaching available to the public, in each case „a line must be drawn between what is in fact made available, and what remains hidden or otherwise has not been made available“.

Relevant question before the EPO : What has been explicitly disclosed in the prior art?

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• 1. Second Medical Use Claims

Patentability

T 1319/04 “Use of nicotinic acid … for the manufacture of a sustained release medicament for use in the treatment of hyperlipidaemia by oral administration once per day prior to sleep …” Prior art: Treatment of hyperlipidaemia using nicotinic acid using a regime of 3 administrations per day

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• 1. Second Medical Use Claims

Patentability

T 1319/04 cont’d G02/08

• 1. “Where it is already known to use a medicament to treat

an illness, Article 54(5) EPC does not exclude that this medicament be patented for use in a different treatment by therapy of the same illness.

• 2. Such patenting is also not excluded where a dosage

regime is the only feature claimed which is not comprised in the state of the art.

• 3. Where the subject matter of a claim is rendered novel
• nly by a new therapeutic use of a medicament, such

claim may no longer have the format of a so called Swiss- type claim, as instituted by decision G5/83.

• 2. German Practice regarding

Infringement/Enforcement of Second Medical Use Claims

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Scope of the Claims of a European Patent

According to the Decision of the Enlarged Board of Appeal of the EPO G 2/88:

• Art. 69 (1) EPC and the according protocol have to

be applied before the EPO and before the national courts of the member states when determining the scope of the patent. However, the rights arising from a patent are determined according to the national law of the member states (Art. 64 (1) EPC).

• 2. Infringement/Enforcement of

Second Medical Use Claims

Claim 1 of EP 0903148: „Use of ribavirin for the manufacture of a pharmaceutical composition for treating a patient having chronic hepatitis C infection to eradicate detectable HCV-RNA by a method comprising administering an effective amount of ribavirin in association with an effective amount of interferon alpha for a time period of 40 - 50 weeks, wherein the patient is one having failed to respond to a previous course of interferon alpha therapy, characterised in that the patient has a viral load of greater than 2 million copies per ml of serum as measured by HCV-RNA quantitative PCR of a HCV genotype 1 infection.“

• 2. Infringement/Enforcement of

Second Medical Use Claims

Ribavirin, LG Düsseldorf, 2004 Alleged infringement activities:

The defendant 1, whose business manager is the defendant 2, produces by order of M. GmbH, Berlin, Ribavirin-capsules with the name “Ribavirin M” with a concentration of 200 mg Ribavirin per capsule. Package leaflet: treatment of HCV as ribavirin monotherapy or as combination therapy with interferon a; no mention of specific patient group The plaintiff argues that patent in suit is infringed through the marketed Ribavirin-capsules directly, alternatively indirectly.

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• 2. Infringement/Enforcement of

Second Medical Use Claims

Ribavirin, LG Düsseldorf, 2004 Direct patent infringement only in case of an “evident preparation” for the patented subject matter. There must be at least directions to a “purposive realization”

• f the claimed specific use of Ribavirin to a considerable

extent. No indirect infringement of the Swiss type claim because defendant does not offer the drug for an act of manufacturing

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• 2. Infringement/Enforcement of

Second Medical Use Claims

Ribavirin, LG Düsseldorf, 2004

• Principle of “evident preparation” or “manifested

arrangement” (“sinnfällige Herrichtung”)

• Looks for some material manifestation in the

manufactured product itself, the packaging, the label, the product leaflet, the SmPC which can be attributed to the new patented use of the drug

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• 2. Infringement/Enforcement of

Second Medical Use Claims

Ribavirin, LG Düsseldorf, 2004 Principle of “evident preparation” in various Federal Court

• f Justice (BGH) landmark decisions:

−1977, “phenyl sulfonyl urea” −1982, “sitosteryl glycosides” −1983, “Hydropyridine” −1990, “slitted covering film”

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• 2. Infringement/Enforcement of

Second Medical Use Claims

OLG Düsseldorf: mere advertising of the drug for the patented use in flyers, marketing materials, advertisements etc. likely not to constitute direct patent infringement as it does not form part

• f a “evident preparation”

− OLG Düsseldorf, 248/4 - Ubichinon Qn − OLG Düsseldorf 2454/11 – Cistus Incanus − LG Düsseldorf, 4a O145/12 Chronic Hepatitis C

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• 2. Infringement/Enforcement of

Second Medical Use Claims

Ribavirin, LG Düsseldorf, 2004 Carving out is possible - “Skinny labelling” No protection for innovator from cross-label use of drug BUT: District Court of Hamburg recently awarded 5 injunctions for indirect infringement

• 3. Indirect Infringement of Second

Medical Use Claims

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• 3. Indirect Infringement of Second

Medical Use Claims

Indirect infringement §10 PatG (German Patent Act) − It is forbidden for any 3rd party without the consent of the patent owner

• To supply or offer to supply within territory a person,
• ther

than a person entitled to use the patented invention, with means relating to an essential element of such invention for using the invention

• Where the 3rd party knows or it is obvious from the

circumstances that such means are suitable and intended for using the invention

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• 3. Indirect Infringement of Second

Medical Use Claims

Indirect infringement - Background

• By German social law, every product with the same particulars as

the prescribed medicinal product must be dispensed if both products are authorised in (at least) one identical indication.

• The Doctor prescribes a medicinal product under its brand name or

its INN with indication of strength, dosage form and package size.

• By default the branded product is prescribed „aut idem“ =

which allows substitution, unless „aut idem“ is crossed out;

• Doctor is, however, under budget pressure, so he will likely not

cross out „aut idem“

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• 3. Indirect Infringement of Second

Medical Use Claims

Indirect infringement - Background − Public health insurance companies may offer discount agreements to pharmaceutical companies; such exclusive agreements are offered via public tenders − The Pharmacist has an obligation to substitute the prescribed medicine by a product for which a discount agreement exists or to dispense one of the three cheapest products that meet the requirements; if he does not, he will not get reimbursed from the health insurance company. − The pharmacist‘s software is fed with all discount agreements and points to cheapest substitute

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• 3. Indirect Infringement of Second

Medical Use Claims

LG Hamburg Warner Lambert, 327 O 140/15 EP 0 934 061 Claim 1: Use of (S)-3-(aminomethyl)-5-methylhexanoic acid (=pregabalin) or a pharmaceutically acceptable salt thereof for the preparation of a pharmaceutical composition for treating pain. Claim 3: …wherein the pain is neuropathic pain.

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• 3. Indirect Infringement of Second

Medical Use Claims

LG Hamburg Warner Lambert, 327 O 140/15 Alleged infringement: Defendant(s)

• marketed their pregabalin with skinny label restricted to

epilepsy and general anxiety disorders (GAD)

• Joined a tender (for pregabalin) of a public health insurer

not limited to the patent-free indications epilepsy and GAD

• Concluded a discount contract for pregabalin with the

public health insurer

• Did not alert the health insurer of the patented indication

„pain“ for pregabalin

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• 3. Indirect Infringement of Second

Medical Use Claims

LG Hamburg Warner Lambert, 327 O 140/15 Decision: Court found that

• defendant supplied means relating to an essential

element of the invention for exploiting the invention

• Defendant knew or it was obvious from the circumstances

that such means are suitable and intended for using the invention

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• 3. Indirect Infringement of Second

Medical Use Claims

Indirect infringement LG Hamburg, Warner Lambert, 327 O 140/15

• skinny

labeling does not prevent from indirect infringement , if the generic company induces patent infringement by joining a discount contract without limitations

• it is obvious and certainly foreseeable that the pharmacist

will substitute the originator drug by the generic drug for all indications

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• 3. Indirect Infringement of Second

Medical Use Claims

Indirect infringement LG Hamburg, Warner Lambert, 327 O 140/15 A drug is already by its production an “evident preparation”

• r “manifested arrangement” for the use in the patent

protected indication, if it can be used without any further effort but only needs to find its assigned purpose

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• 4. Direct Infringement of Second

Medical Use Claims „Oestrogen Blocker“

Direct infringement in case of cross-label use OLG Düsseldorf, Oestrogen Blocker, I-2 W 6/17 Skinny-labelled product was found to infringe patent Two requirements: a) Suitability of medicament for patented purpose b) Defendant takes advantage

• f

circumstances which, similar to an evident preparation, will lead to use of medicament according to the patent

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• 4. Direct Infringement of Second

Medical Use Claims „Oestrogen Blocker“

Requirement b) may likely be fulfilled in case of cross-label use, if defendant takes advantage of German substitution practice, and such substitution practice occurs in the specific individual case. For a finding of infringement patentee may have to show that generic product will indeed be substituted against innovator drug for patented indication.

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• 4. Direct Infringement of Second

Medical Use Claims „Oestrogen Blocker“

Decision leaves open which measures the generic manufacturer should take in order to avoid patent infringement Possible measures may be:

• Change of advertising material
• Exchange of information with health insurance companies
• Communications to wholesalers and/or pharmacists
• Incorporation of information into databases of pharmacies

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• 4. Direct Infringement of Second

Medical Use Claims „Oestrogen Blocker“

Skinny labelling no longer will prevent a finding of patent infringement Liability of generic manufacturers has increased

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• 4. Infringement of Second Medical Use

Claims

…. And the future? Watch this space and stay tuned!

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• 5. Summary Enforcement of Second

Medical Use Claims

An evident preparation for the claimed (2nd medical) use can happen e.g. by:

• adding label instructions which describe the patented use,
• by confectioning or ready-to-use preparation of the medicament
• By applying for a tender that is not limited to patent free indications

Evident preparation no longer is necessary for a finding of patent infringement, “suitability for the patented purpose” and “other circumstances” may be sufficient

• Dr. Markus Engelhard

engelhard@boehmert.de Pettenkoferstraße 20-22 80336 München Boehmert & Boehmert Germany

Thank you for your attention !