Patendinõudlus eluteaduste valdkonnas

Eluteaduste valdkonna intellektuaalse omandi kaitsePatendiotsing, patendinõudlus

Margus Sarap, Euroopa patendivolinik17.aprill 2013, Tartu Biotehnoloogia Park

Biotehnoloogia erisused?

4/2/2013 2Margus Sarap, 2013

Mittepatenditavad:

bioloogilisi meetodeid

bioloogilise aine, taime või looma saamiseks

välja arvatud mikrobioloogilised meetodid mikroorganismide saamiseks

leiutised, mida saab kasutada ainult ühe kindla taimesordi või loomatõu puhul

NB! Bioloogilise aine, taime või looma saamise olemuselt bioloogiline meetod on meetod, mis täielikult põhineb looduslikul nähtusel, nagu ristamine ja selektsioon.


4/2/2013 3Margus Sarap, 2013

NB!

Ühe ja sama patenditaotlusega saab taotleda patendikaitset ainult ühele leiutisele või ühtse leiundusliku mõttega seotud leiutiste kombinatsioonile


4/2/2013 4Margus Sarap, 2013


1. A fluorescent probe for determining protein kinase activity with the general formula (I):

(X-Y-Z)-L-F (I),wherein

X-Y-Z is a bisubstrate-analog inhibitor of a protein kinase, in which X is a compound that binds to the ATP-binding pocket of the kinase and;

Z is a compound that binds to the protein/peptide-binding domain of the kinase;

Y is a an organic tether that connects X and Z and permits simultaneous binding of X and Z to the active site of the kinase;

F is a fluorescent dye which optical characteristics are changed in the course of the binding of (X-Y-Z)-L-F to the kinase;

L is a linker (between the bisubstrate-analog inhibitor XYZ and fluorescent label F) formed of a hydrocarbon chain, of other type of organic molecule or of part of organic molecule; may be omitted in the probe and F directly bound to inhibitor XYZ.

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1. A fluorescent probe for a protein kinase selected from the group consisting of:

2. A kit comprising a fluorescent probe of claim 1. 3. A bisubstrate-analog inhibitor of a basophilic protein kinase selected from the group

consisting of:

4. A method for determining the fraction of an active binding form of a protein kinase in a sample containing a fluorescent probe of claim 1 ...

NO

N

N

OHOHN

NH2O

N

O

N+

-OOC

O

NH

O

NH-(D-Arg)6-(D-Lys)-C(=O)-NH2NH

N

S OO

HNNH

O

NH-(D-Arg)6-D-Lys(5-TAMRA)-C(O)NH2 NO

N

N

OHOH

N

NH2

O

O

NH-(D-Arg)6-(D-Lys)-C(=O)-NH2

NNO

O2N

NH

NH

NO

N

N

OHOHN

NH2O

N

O

N+

-OOC

O

NH

O

NH-(D-Arg)6-(D-Lys)-C(=O)-NH2NH

N

S OO

HNNH

O

NH-(D-Arg)6-D-Lys(5-TAMRA)-C(O)NH2 NO

N

N

OHOH

N

NH2

O

O

NH-(D-Arg)6-(D-Lys)-C(=O)-NH2

NNO

O2N

NH

NH

4/2/2013 6Margus Sarap, 2013

patent US8,158,376

Patendidokumendi ülesehitus?

•Leiutiskirjeldus – specification–Pealkiri - Title–Tehnika valdkond – Technical Field–Tehnika tase – Background Art–Leiutise olemus – Summary of invention–Jooniste loetelu – Brief description od drawings–Teostusnäi(de)ted – Description of embodiments–Viited – Recitation list–Patendinõudlus - Claims–Lühikokkuvõte - Abstract–Joonised - Drawings

9.12.2011 7Sarap ja Partnerid, ©2011

Patendidokumendi erinevate osade tähendus?

Kõige tähtsam – patendinõudlus

tehnilise lahenduse (leiutise) kaitseulatus

sõltumatu punkt

sõltuvad punktid


Patendidokumendi erinevate osade tähendus?

Leiutiskirjeldus

leiutise olemuse avamine

tehnilise lahenduse täpne kirjeldus


Vähiravi

Explanation of terms• Heat shock protein 90 (HSP 90)

Belongs to a class of proteins that protect cells when stressed by elevated temperatures; assists in tumour repression.

• Heat shock protein 90 inhibitor (HSP 90 inhibitor)Compounds which block the functioning of HSP 90. Examples: geldanamycin or 17-alkylamino-17-desmethoxygeldanamycin (17-AAG).

• Platinum coordination complexesPlatinum complexed with ligands. These compounds are used as chemotherapeutics. Examples: cisplatin, carboplatin, oxaliplatin.

17-AAG, R17 = alkylamino

Oxaliplatin

Allikas EPO materjalid , nõudluse tõlgendamine

LeiutisAn improved way of treating people suffering from breast cancer by injecting a platinum coordination complex and optionallyalso an HSP 90 inhibitor.The invention shows improved results by combining the two compounds. The specific combination of oxaliplatin and 17-AAG has a synergistic effect.

How can you protect it from imitation?

• "An improved way" → Compared with what? (term not clear)

• "Way of treating people" → Method of treatment of the human or animal body by therapy = excluded from patentability

• "A platinum coordination → Not a "method of treatment"; has a

complex " technical function → possible patent


Patent Claim: "A platinum coordination complex"

How to patent this invention: claim it!

Claiming a platinum coordination complex in general means trying to get very broad protection. You already know that such complexes have been described before.

Patent Claim: "A platinum coordination complex for use in the treatment of suffering people."

This wording also does not describe what you invented.

Patent Claim: "A platinum coordination complex for use in the treatment of breast cancer."

A prior art search will show whether the invention – as claimed – is actually new.


Tehnika taseme otsingu tulemused

The prior art search found a journal article that discloses the invention.

Cancer Treatment Reports 67(3) 235-238, 1983

"... 2 [patients] with adrenocarcinomas in the breast ... were treated

with cisplatin at a dose of 60 mg/m2 ..."

A platinum coordination complex (i.e. cisplatin) for use in the treatment

of cancer is already known from this journal article!


Comparison of the two inventions

The invention

as claimedCancer Treatment Reports

"A platinum coordination

complex for use in the

treatment of breast cancer."

"... 2 [patients] with

adrenocarcinomas in the

breast ... were treated

with cisplatin at a dose of 60

mg/m2 ..."

"A combination of a platinum

coordination complex and an

HSP 90 inhibitor for use ..."

• New• Inventive step

(the combined use shows

improved effects)


Not new

Leiutist kaitsev nõudlus

Claim to be filed:

"A combination of a platinum coordination complex and an HSP 90 inhibitor for use in the treatment of breast cancer."


Sõltumatute nõudluste kasutamine kaitse täiendamiseks

The patent should include both broad and specific claims.

Broad: An independent claim (i.e. a claim stating the essential features of the invention) helps prevent the patent from being circumvented.

Specific: Dependent claims refer to an independent claim and additionally define preferred embodiments of the invention.

Independent claim

Dependent claim 1

Dependent claim 2


Patendiametile (EPO) esitatud taotlus

CLAIM 1:"A combination of a platinum coordination complex and an HSP 90 inhibitor for use in the treatment of breast cancer."

Claim 2: "A combination according to claim 1, characterised in that the HSP 90 inhibitor is 17-AAG."

Claim 3: "A combination according to claim 1, characterised in that the platinum coordination complex is oxaliplatin."

The patent office will perform its own prior art search and thenconsider whether the invention AS CLAIMED is new and non-obvious.

Claim 4: "A combination according to claim 2, characterised in that the platinum coordination complex is oxaliplatin."


Tehnika tase EPO otsingust

"Combination of HSP 90 inhibitor ... with anticancer agents like carboplatin or cisplatin ... to inhibit ... growth of breast cancer cells."

"Methods for enhancing the efficacy of cytotoxic agents through the use of HSP90 inhibitors"

EPO arvamus

Applicant's claim:

"A combination of a platinum

coordination complex and an HSP 90

inhibitor for use in the treatment of

breast cancer."

The invention according to claim 1

is already shown and claimed in

WO 02/15925.

EPO response:

Please amend your claims if you want your invention patented!

A platinum coordination complex

(e.g. cisplatin) and an HSP 90

inhibitor were used in

WO 02/15925 to treat breast

cancer.

Edasine analüüs

• Check the material revealed in the prior art searches:• Does the invention have any features NOT disclosed in the

prior art?• What are the advantages of the invention compared with

the prior art?

How can the claims be amended to reflect the invention in a way that it is new (considering all the prior art)?

• Did the EPO interpret any important features of the invention differently to the inventor?

Applicant's reply: amendments to the application, explanation of the relationship between the invention and the prior art

Synergism (more than additive)

Claim 2: Features of Claim 1 + HSP90 inhibitor = 17-AAG

Claim 4: Features of Claims 1 + 2 + Pt coordination complex = oxaliplatin

Cancer TreatmentReports

Improved effect (additive)

Claim 3: Features of Claim 1 +Pt coordination complex = oxaliplatin

Claim 1: Combination of HSP 90 inhibitor and Pt coordination complex

Leiutise võrdlus tehnika tasemega

Technical features of the invention

WO 02/15925

Advantages/technical result

No

No

No No

No

No

No

No

No

No

Analüüsi tulemusAlthough the individual elements of the invention are known, the combination of specific compounds is not and it produces a new, unique benefit. But you have to take into account that:

Claim 2 refers to the use of 17-AAG. To use this specific HSP 90 inhibitor is considered to be trivial, because WO 02/15925 recommends using any HSP 90 inhibitor in combination with an anticancer agent.

Claim 3 teaches the use of oxaliplatin. Again, since WO 02/15925 hints at the use of any anticancer drug, the use of oxaliplatin is also considered to be obvious.

Claim 4 describes the use of the combination of oxaliplatin and 17-AAG. It is shown in the patent application that the combination produces a synergistic (= more than additive) effect. This is not disclosed in

WO 02/15925.

Analüüsi tulemusedIf one compound is simply replaced by another without showing any unexpected or surprising effect, such a replacement is frequently considered to represent routine for an expert.

If an unexpected or surprising effect can be shown, then the invention is often considered to be inventive (i.e. the invention is not obvious for an expert working in the technical field).

The use of 17-AAG and oxaliplatin, which leads to an unexpected synergistic combination, is therefore inventive.

Invention(new + inventive)

R17 = alkylamino

The present invention provides a method for treating cancer. The

method involves the administration of an HSP90 inhibitor and a

platinum coordination complex, where the combined administration

provides a synergistic effect.

The HSP90 inhibitor for this aspect is typically 17-AAG, while the

platinum coordination complex is oxaliplatin.

17-AAG combination in SKSBr-3 cells [0093] The following table

provides CI values for combinations of 17-AAG and the platinum

complexes oxaliplatin and cisplatin in an SKBr-3 cell assay ...

EPOsse esitatud kirjeldus toetab parandusi

Differentto "Cancer Treatment…"

Differentto patentWO02/…

Supports inventive step:differenttechnical result

Väljaantud patendi nõudlus

Claim 1 as granted reads:

"Medicament comprising 17-Alkylamino-17-desmethoxygeldanamycin

(17-AAG) and oxaliplatin for use in the treatment of breast cancer

in a patient."

Response from EPO: granted!

EP1179050• 1. A method for removal of protein kinase from a liquid

containing the protein kinase by contacting the liquid with a carrier bound affinity ligand for the kinase, characterized in that the ligand is a bisubstrate inhibitor for the kinase whereas the ligand is attached to the carrier.

• 2. The method of claim 1, characterized in that the bisubstrate inhibitor comprises the structure

• C-(L) n-N• where• (a) C contains a structure inhibiting binding of the

peptide/protein substrate to the protein kinase,• (b) L is an organic linker,• (c) n is an integer 0 or 1, and• (d) N is an inhibitor competitively inhibiting binding of the

nucleoside triphosphate (NTP) to the protein kinase;• and the structure is attached to the carrier via C.• 3. The method of any one of claims 1-2, characterized in that C is

a peptide substrate consensus sequence or a pseudosubstrate consensus sequence. 4/2/2013 Margus Sarap, 2013 26

Näide

4/2/2013 Margus Sarap, 2013 27

• 1. A method for removal of protein kinase from a liquid containing the protein kinase by contacting the liquid with a carrier bound affinity ligand for the kinase, characterized in that the affinity ligand is a bisubstrate inhibitor having a structure containing

• - a moiety having the structure that is able to competitively inhibit binding of the relevant nucleotide triphosphate (NTP) and

• - a moiety having the structure that is able to competitively inhibit binding of peptide or protein substrate

• to the particular protein kinase molecule whereas the ligand is attached to the carrier.

• 2. The method of claim 1, characterized in that the bisubstrate inhibitor for the particular protein kinase molecule comprises the structure

• C-(L) n-N• where• (a) C contains a structure inhibiting binding of the peptide or protein

substrate to the protein kinase,• (b) L is an organic linker,• (c) n is an integer 0 or 1, and• (d) N is an inhibitor competitively inhibiting binding of the nucleoside

triphosphate (NTP) to the protein kinase.• 3. The method of any one of claims 1-2, characterized in that C is a peptide

substrate consensus sequence or a pseudosubstrate consensus sequence.

• 1. A method for removal of protein kinase from a liquid containing the protein kinase by contacting the liquid with an affinity ligand for the kinase bound to a carrier insoluble in aqueous media, characterized in that the affinity ligand is a bisubstrate inhibitor having a structure containing simultaneously

• - a moiety having the structure that is able to competitively inhibit binding of the relevant nucleotide triphosphate (NTP) and

• - a non-phosphorylatable moiety having the structure that is able to competitively inhibit binding of peptide or protein substrate

• whereas both moieties target the particular protein kinase molecule whereas the ligand is attached to the carrier.

• 2. The method of claim 1, characterized in that the bisubstrate inhibitor for the particular protein kinase molecule comprises the structure

• C-(L)n-N• where• (a) C contains a structure inhibiting binding of the peptide or protein substrate to

the protein kinase,• (b) L is an organic linker,• (c) n is an integer 0 or 1, and• (d) N is an inhibitor competitively inhibiting binding of the nucleoside triphosphate

(NTP) to the protein kinase.• 3. The method of any one of claims 1-2, characterized in that C is a peptide substrate

consensus sequence or a pseudosubstrate consensus sequence.

4/2/2013 Margus Sarap, 2013 28

4/2/2013 Margus Sarap, 2013 29

Claims1. A method for removal of protein kinase from a liquid containing the protein kinase by contacting the liquid with an affinity ligand for the kinase bound to a carrier insoluble in aqueous media characterized in that the affinity ligand is a bisubstrate inhibitor having a structure containing simultaneously- a moiety having the structure that is able to competitively inhibit binding of the relevant nucleotide triphosphate (NTP) and- a non-phosphorylatable moiety having the structure that is able to competitively inhibit binding of peptide orprotein substrate whereas both moieties target the particular protein kinase molecule whereas the ligand is attached to the carrier.2. The method of claim 1, characterized in that the bisubstrate inhibitor for the particular protein kinase molecule comprises the structureC-(L)n-Nwhere(a) C contains a structure inhibiting binding of the peptide or protein substrate to the protein kinase,(b) L is an organic linker,(c) n is an integer 0 or 1, and(d) N is an inhibitor competitively inhibiting binding of the nucleoside triphosphate (NTP) to the protein kinase.3. The method of any one of claim 2, characterized in that C is a peptide substrate consensus sequence or a pseudosubstrate consensus sequence.

Nõudlused kellele

•taotleja -> võimalikult lai kaitse•Patendiameti ekspert -> tehnika tase -> kitsendamine•konkurent

• patendi vaidlustamine’• rikkumine

•rikkuja

4/2/2013 Margus Sarap, 2013 30

EE03157•1. Optiliselt puhas ühend, mida iseloomustab see,

et ühend on (-)-5-metoksü-2-{[(4-metoksü-3,5-dimetüül-2-püridinüül)metüül]sulfinüül]-H-bensimidasooli Na+-, Mg2+-, Li+-, K+- Ca2+- või N+(R)4-sool, milles R on alküülrühm 1-4 süsinikuaatomiga.

4/2/2013 Margus Sarap, 2013 31

Küsimused?-Mis on optilise puhtuse määr-tehnika tasemest tuntud Na, Mg soolad

Küsimused?

Sarap ja Partnerid PatendibürooMargus [email protected] tel 747 7058Kompanii 1c, Tartu

Mikk [email protected] tel 53 039 088 Soo 46, Tallinn

4/2/2013 32Margus Sarap, 2013

www.patent.ee

http://www.patent.ee/

Technology

Patendinõudlus eluteaduste valdkonnas