• 沒有找到結果。

In order to define the scope of analysis, which is the list of patents to be analyzed, two different patent search strategies are used. The results of two different search strategies will be pulled together in order to obtain the most comprehensive scope. The two concepts of patent search are listed below.

1. Patent search based on technological terms;

2. Patent search based on inventors.

The official website of United State Patent & Trademark Office (USPTO) Full-text and Image Database is the database used and thus only granted patents are searched. The scope of protection provided in a patent is the claims. For a pending application, the claim is still subject to change and is usually very

different from its granted version. It is of no use to analyze uncertain claim scope, therefore only the granted patents with certain and fixed claim scope are

employed in this study. Patent search queries and details are shown in Table 1.

Table 1: Patent Search History Source: Organized and searched by this study

Search

Category Keyword Used Quantity Reviewd Date of

Search Database

Inventors

Buchdunger; Elisabeth; Capdeville;

Renaud; Demetri; George Daniel;

Dimitrijevic; Sasa; Druker; Brian Jay;

Fletcher; Jonathan A.; Heinrich;

Michael C.; Joensuu; Heikki;

Silberman; Sandra Leta; Tuveson;

David; Wang Yanfeng; Paul Manley

80 34 2014/5/12

Technology and Patentee

imatinib, gleevec, glivec, STI571,

Novartis, ciba, geigy, sandoz 35 11 2014/5/22 USPTO Granted

Patents

Total 40*

* There is no duplicate patent (with same patent number) in the final total 40 patents.

40

Two different patent search strategies will be discussed separately below.

The technology terms are the trademarks, generic names, code names in R&D, and chemical names of the drug Imatinib. Chemical names are very general terms and many patents irrelevant to Gleevec are included to give more than thousands of hits (data not shown). In addition, chemical name of Imatinib (Gleevec) can also be named in different ways. For example,

N-[4-methyl-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)-phenyl]-4-(4-methyl-pipera zin-1-ylmethyl)-benzamide,

4-[(4-methyl-1-piperazinyl)methyl]-N-[4-methyl-3-[[4-(3-pyridinyl)-2-pyrimidin yl]amino]-phenyl] benzamide, and

N-{5-[4-(4-methyl-piperazino-methyl)-benzoylamido]-2-methylphenyl}-4-(3-pyr idyl)-2-pyrimidine-amine are literally different but are actually all the same and are the chemical names of Imatinib. Therefore, it would be impractical to use chemical name to search Gleevec-related patents. Instead, trademarks, code name in R&D, and generic names of Gleevec are used.

The results of using chemical names to search patents still gave a large number of hits (search history not shown in Table 1). A preliminary review of these patents showed that most of them are not relevant to the study. Gleevec is either a similar drug cited in those patents or cited as a comparison to the actual claimed inventions in experiments. Thus, in order to narrow down the scope of analysis, patent owner/assignee limitation is added. Gleevec is known to be

studied and developed by Novartis, which was previously Ciba Geigy and Sandoz.

All three companies are used as the keywords in the patent applicant limitation query. The search result of technological term is 35 granted US utility patents.

Within these 35 patents, there are still unrelated patents. A preliminary review on the titles, abstracts and claims of patents is carried out to determine whether the patents are relevant. After preliminary review, the final result of the analysis scope from technological keywords is 11 patents.

41

Every patent needs at least one inventor in order to be granted. Inventor keywords are widely used when the technology is specific, such as in this case. At the beginning, the inventors of Imatinib are identified by a) inventors of patents listed in orange book

104

, and b) academic papers. Relevant inventors are searched as in Table 1. The search result of inventor keywords is 80. After reviewing the abstracts and the titles of each of the 80 patents searched, 34 patents are

determined to be relevant to the scope of analysis.

Therefore, taking the results from technological and inventor keyword searches together, a total number of 40 patents will be the final scope of analysis of this study. It is to be noted that 11 patents from technological keyword and 34 from inventor keyword give only 40, instead of 45, because there are duplicates in the searches. The 40 patents are listed in Table 2 below.

104

Orange book is the publication, Approved Drug Products with Therapeutic Equivalence Evaluations,

which identifies drug products approved on the basis of safety and effectiveness by the FDA. Patent

information of an approved small molecular chemical drug can be accessed in the orange book. Such

information is submitted by the applicant and is related to the patent exclusivity extension.

42 Table 2: Patent List of the Scope of the Analysis

Patent No. Title Abstract Issued Date Application Date Inventor Original Assignee

US5521184 Pyrimidine derivatives and processes for the preparation thereof

There are described N-phenyl-2-pyrimidine-amine derivatives of formula I ##STR1##

wherein R.sub.1 is 4-pyrazinyl, 1-methyl-1H-pyrrolyl, amino- or amino-lower alkyl-substituted phenyl wherein the amino group in each case is free, alkylated or acylated, 1H-indolyl or 1H-imidazolyl bonded at a five-membered ring carbon atom, or unsubstituted or lower alkyl-substituted pyridyl bonded at a ring carbon atom and unsubstituted or substituted at the nitrogen atom by oxygen, R.sup.2, R.sup.3, R.sup.9, X, Y, n and R.sup.10 are defined in claim 1 These compounds can be used, for example, in the therapy of tumoral diseases.

1996/05/28 1994/04/28 Zimmermann; Jurg Ciba-Geigy Corporation

US5705502

Pharmacologically active pyrimidineamine derivatives and processes for the preparation thereof

Described are N-phenyl-2-pyrimidineamine derivatives of formula I ##STR1## wherein R.sub.1 is a substituted cyclic radical, the cyclic radical being bonded at a ring carbon atom in each case and being selected from phenyl, pyridyl, pyrazinyl, thiazolyl, pyrimidinyl, pyridazinyl and imidazolyl, and the substituents of the above-mentioned cyclic radical being selected from one or more of the groups halogen, cyano, carbamoyl, C(.dbd.O)OR.sub.3, C(.dbd.O)R.sub.4, SO.sub.2 N(R.sub.5)R.sub.6, --N(R.sub.7)--R.sub.8, --OR.sub.9 and fluorine-substituted lower alkyl, wherein R.sub.3, R.sub.4, R.sub.5, R.sub.6, R.sub.7, R.sub.8 and R.sub.9 are each independently of the others hydrogen or lower alkyl that is unsubstituted or substituted by mono- or di-lower alkylamino; and R.sub.2 is selected from halogen, cyano, carbamoyl, --C(.dbd.O)--OR.sub.10, --C(.dbd.O)--R.sub.11, --SO.sub.2 --N(R.sub.12)--R.sub.13, --N(R.sub.14)--R.sub.15, --OR.sub.16 and fluorine-substituted lower alkyl, wherein R.sub.10, R.sub.11, R.sub.12, R.sub.13, R.sub.14, R.sub.15 and R.sub.16 are each independently of the others hydrogen or lower alkyl that is unsubstituted or substituted by mono- or di-lower alkylamino. Those compounds can be used, for example, in the treatment of tumour diseases.

1998/01/06 1995/05/31 Zimmermann; Jurg Novartis Corporation

US5728708

Pharmacologically active pyridine derivatives and processes for the preparation thereof

N-phenyl-2-pyrimidineamine derivatives of formula I ##STR1## wherein the substituents are as defined in claim 1 and the derivatives of formula I can be used, for example, in the

treatment of tumour diseases. 1998/03/17 1995/05/31 Zimmermann; Jurg Novartis Corporation

US6894051

Crystal modification of a N-phenyl-2-pyrimidineamine derivative, processes for its manufacture and its use

The invention relates to a new crystalline form of the methanesulfonic acid addition salt of 4(4methylpiperazin1ylmethyl)N[4methyl3(4pyridin3yl)pyrimidin2 -ylamino)phenyl]benzamide of formula 1, which may be used for example for tumor therapy.

2005/05/17 2000/01/18 Zimmermann; Jurg; Sutter; Bertrand; Burger;

Hans Michael Novartis AG

US6958335 Treatment of gastrointestinal stromal tumors

4-(4-methylpiperazin-1-ylmethyl)-N-[4-methyl-3-(4-pyridin-3-yl)pyrimidin-2-ylamino)phenyl]-benzamide of the formula I ##STR1## or a pharmaceutically acceptable salt thereof can be used in the treatment of gastrointestinal stromal tumours.

2005/10/25 2003/08/11

Buchdunger; Elisabeth; Capdeville; Renaud;

Demetri; George Daniel; Dimitrijevic; Sasa;

Druker; Brian Jay; Fletcher; Jonathan A.;

Heinrich; Michael C.; Joensuu; Heikki;

Silberman; Sandra Leta; Tuveson; David

Novartis AG; Dana-Farber Cancer Institute,

Inc.; Oregon Health &

Science University

43

US7081532 N-phenyl-2-pyrimidine-amine derivatives

The invention relates to N-phenyl-2-pyrimidine-amine derivatives of formula (I)

##STR00001## wherein the substituents are defined as in the description, to processes for the preparation thereof, to medicaments comprising those compounds, and the use thereof in the preparation of pharmaceutical compositions for the therapeutic treatment of warm-blooded animals, including humans.

2006/07/25 2001/09/11

Buerger; Hans M; Caravatti; Giorgio;

Zimmermann; Juerg; Manley; Paul W;

Breitenstein; Werner; Cudd; Margaret A

Novartis AG

US7312216 N-phenyl-2-pyrimidine-amine derivatives

The invention relates to N-phenyl-2-pyrimidine-amine derivatives of formula I

##STR00001## wherein the substituents are defined as indicated in the description, to processes for the preparation thereof, to medicaments comprising those compounds, and to the use thereof in the preparation of pharmaceutical compositions for the therapeutic treatment of warm-blooded animals, including humans.

2007/12/25 2006/06/07

Buerger; Hans M; Caravatti; Giorgio;

Zimmermann; Uerg; Manley; Paul W;

Breitenstein; Werner; Cudd; Margaret A

Novartis AG

US7329661 N-phenyl-3-pyrimidine-amine derivatives

The invention relates to N-phenyl-2-pyrimidine-amine derivatives of formula I

##STR00001## wherein the substituents are defined as indicated in the description, to processes for the preparation thereof, to medicaments comprising those compounds, and to the use thereof in the preparation of pharmaceutical compositions for the therapeutic treatment of warm-blooded animals, including humans.

2008/02/12 2007/07/26

Buerger; Hans Michael; Caravatti; Giorgio;

Zimmerman; Juerg; Manley; Paul William;

Breitenstein; Werner; Cudd; Margaret Amelia

Novartis AG

US7456283 N-phenyl-2-pyrimidine-amine derivatives

The present invention relates to novel amides and a process for preparing these amides.

2008/11/25 2003/02/06

Loiseleur; Olivier; Kaufmann; Daniel; Abel;

Stephan; Burger; Hans Michael; Meisenbach;

Mark; Schmitz; Beat; Sedelmeier; Gottfried

Novartis AG

US7544799

Crystal modification of a N-phenyl-2-pyrimidineamine derivative, processes for its manufacture and its use

The invention relates to a new crystalline form of the methanesulfonic acid addition salt of 4-(4-methylpiperazin-1-ylmethyl)-N-[4-methyl-3-(4-pyridin-3-yl)pyrimidin-- 2-ylamino)phenyl]-benzamide of formula 1, which may be used for example for tumour therapy. ##STR00001##

2009/06/09 2006/09/05 Zimmermann; Jurg; Sutter; Bertrand; Burger;

Hans M Novartis AG

US7557105 N-oxides of N-phenyl-2-pyrimidine-amine derivatives

The invention relates to N-phenyl-2-pyrimidine-amine derivatives in which at least one nitrogen atom carries an oxygen atom to form the corresponding N-oxides, to processes for the preparation thereof, to pharmaceutical compositions comprising those

compounds, and to the use thereof in the preparation of pharmaceutical compositions for the therapeutic treatment of warm-blooded animals, including humans.

2009/07/07 2003/01/22

Bornsen; Klaus Olaf; End; Peter; Gross;

Gerhard; Pfaar; Ulrike; Manley; Paul William;

Zimmermann; Jurg

Novartis AG

US7579467 N-phenyl-2-pyrimidine-amine derivatives

The present invention relates to novel amides and a process for preparing these amides.

2009/08/25 2007/08/28

Loiseleur; Olivier; Kaufmann; Daniel; Abel;

Stephan; Burger; Hans Michael; Meisenbach;

Mark; Schmitz; Beat; Sedelmeier; Gottfried

Novartis AG

US7655669 Pyrimidineamide derivatives and the use thereof

The invention relates to novel substituted N-(3-benzoylaminophenyl)-4-pyridyl-2-pyrimidinamine derivatives, processes for the preparation thereof, pharmaceutical compositions containing same, the use thereof optionally in combination with one or more other pharmaceutically active compounds for the therapy of a disease which responds to an inhibition of protein kinase activity, especially a neoplastic disease, and a method for the treatment of such a disease.

2010/02/02 2003/09/26 Manley; Paul William; Breitenstein; Werner;

Jacob; Sandra; Furet; Pascal Novartis AG

44

US7723339

Combination comprising a signal transduction inhibitor and an epothilone derivative

The present invention relates to a combination comprising N-{5-[4-(4-methyl-piperazino-methyl) -benzoylamido]-2-methylphenyl}-4-(3-pyridyl)-2-pyrimidine-amine and an epothiione derivative; pharmaceutical composition comprising said combination; method of treatment comprising said combination; and commercial packages comprising said combination.

2010/05/25 2002/02/26

Brandt; Ralf; Buchdunger; Elisabeth; Heldin;

Carl-Henrik; Ostman; Arne; Pietras; Kristian;

O'Reilly; Terence; Rothermel; John D; Traxler;

Peter; Wartmann; Markus

Novartis AG

US7767688

Combination of pyrimidylaminobenzamide compounds and imatinib for treating gastrointestinal stromal tumours

The invention provides a pharmaceutical combination comprising: a) a

pyrimidylaminobenzamide compound, and b) imatinib. and a method for treating or preventing a proliferative disease, especially GIST, using such a combination.

2010/08/03 2006/06/02 Alland; Leila; Manley; Paul W; Mestan;

Juergen Novartis AG

US7816359 N-phenyl-2-pyrimidine-amine derivatives

The present invention relates to novel amides and a process for preparing these amides.

2010/10/19 2007/08/28

Loiseleur; Olivier; Kaufmann; Daniel; Abel;

Stephan; Burger; Hans Michael; Meisenbach;

Mark; Schmitz; Beat; Sedelmeier; Gottfried

Novartis AG

US7825247 N-phenyl-2-pyrimidine-amine derivatives

The present invention relates to novel amides and a process for preparing these amides.

2010/11/02 2007/08/28

Loiseleur; Olivier; Kaufmann; Daniel; Abel;

Stephan; Burger; Hans Michael; Meisenbach;

Mark; Schmitz; Beat; Sedelmeier; Gottfried

Novartis AG

US7879860 Delta and epsilon crystal forms of Imatinib mesylate

The invention relates to the delta and epsilon crystal form of the methanesulfonic acid addition salt of 4(4methylpiperazin1ylmethyl)N[4methyl3(4(pyridin3yl)pyrimidin -2 -ylamino)phenyl]-benzamide (the compound of formula I, see below), certain processes for their preparation, pharmaceutical compositions containing these crystal forms, and their use in diagnostic methods or for the therapeutic treatment of warm-blooded animals, and their use as an intermediate or for the preparation of pharmaceutical preparations for use in diagnostic methods or for the therapeutic treatment of warm-blooded animals, especially humans.

2011/02/01 2006/08/24 Mutz; Michael Novartis AG

US7879868

Use of imatinib (glivec,sti-571) to inhibit breast cancer resistance protein (BCRP)-mediated resistance to therapeutic agents

The present invention relates to the use of imatinib of the following formula

##STR00001## or a pharmaceutically acceptable salt thereof, for the preparation of a medicament for the treatment of a cancer that expresses breast cancer resistant protein

(BCRP) in a human subject in need of such a treatment. 2011/02/01 2003/10/10 Houghton; Peter J.; Traxler; Peter Novartis AG

US7893076 Crystalline form F of Imatinib mesylate

The invention relates to the F-crystal form, G-crystal form, H-crystal form, I-crystal form and K-crystal form of the methanesulfonic acid addition salt of 4-(4-methylpiperazin-1-ylmethyl)-N-[4-methyl-3-(4-(pyridin-3-yl)pyrimidin- -2-ylamino)phenyl]-benzamide, certain processes for their preparation, pharmaceutical compositions containing these crystal forms, their use in diagnostic methods or for the therapeutic treatment of warm-blooded animals, and their use as an intermediate or for the preparation of pharmaceutical preparations for use in diagnostic methods or for the therapeutic treatment of warm-blooded animals, especially humans.

2011/02/22 2006/11/23 Mutz; Michael Novartis AG; Novartis

Pharma GmbH

45

US7956053 Inhibitors of tyrosine kinases

The invention relates to compounds of formula ##STR00001## wherein the substituents R1, R2 and R4 have the meaning as set forth and explained in the description of the invention, to processes for the preparation of these compounds, pharmaceutical compositions containing same, the use thereof optionally in combination with one or more other pharmaceutically active compounds for the therapy of a disease which responds to an inhibition of protein kinase activity, especially a neoplastic disease, in particular leukaemia, and a method for the treatment of such a disease.

2011/06/07 2009/06/22 Breitenstein; Werner; Furet; Pascal; Jacob;

Sandra; Manley; Paul W Novartis AG

US8017621 Inhibitors of the mutant form of kit

The present invention relates to the treatment of KIT dependent diseases that are characterized by a mutant form of KIT whereby the mutant KIT is identified and an appropriate inhibitor of the mutant KIT selected form midostaurin, vatalanib and

compound A is administered. ##STR00001## 2011/09/13 2004/11/17 Buchdunger; Elisabeth; Fabbro; Doriano Novartis AG

US8026247 Bicyclic amides as kinase inhibitors

The invention relates to compounds of formula (I) and their use in the treatment of the animal or human body, to pharmaceutical compositions comprising a compound of formula I and to the use of a compound of formula I for the preparation of pharmaceutical compositions for use in the treatment of protein kinase dependent diseases, especially of proliferative diseases, such as in particular tumour diseases.

2008/11/20 2005/09/14

Guido Bold; Hans-Georg Capraro; Giorgio Caravatti; Andreas Floersheimer; Pascal Furet;

Paul W. Manley; Andrea Vaupel

Novartis AG

The present invention relates to the use of pyrimidylaminobenzamide compounds for the preparation of a drug for the treatment of diseases that respond to modulation of Ephrin receptor kinase, especially EphB4, activity, especially for the curative and/or prophylactic treatment of proliferative diseases, and to a method of treating diseases that respond to

modulation of kinase activity, especially Ephrin receptor kinase activity. 2012/01/10 2007/05/23 Manley; Paul W; Martiny-Baron; Georg;

Mestan; Juergen Novartis AG

US8124611 Inhibitors of the mutant form of kit

The present invention relates to the treatment of KIT dependent diseases that are characterized by a mutant form of KIT whereby the mutant KIT is identified and an

appropriate inhibitor of the mutant KIT is administered. 2012/02/28 2010/02/04 Buchdunger; Elisabeth; Fabbro; Doriano Novartis AG

US8163904 -3-(4-pyridin-3-yl-pyrimidin-2-ylamino)-benzamide are prepared by various processes.

2012/04/24 2006/07/18

Manley; Paul W; Shieh; Wen-Chung; Sutton;

Paul Allen; Karpinski; Piotr H; Wu; Raeann;

Monnier; Stephanie; Brozio; Jorg

Novartis AG; Novartis Pharma GmbH

US8198289 Crystal form H imatinib mesylate for pharmaceutical use

The invention relates to particular crystal forms of the methanesulfonic acid addition salt of 4-(4 -methylpiperazin-1-ylmethyl)-N-[4-methyl-3-(4-(pyridin-3-yl)pyrimidin-2-y-lamino)phenyl]-benzamide, ##STR00001## certain processes for their preparation, pharmaceutical compositions containing these crystal forms, and their use in diagnostic methods or, preferably, for the therapeutic treatment of warm-blooded animals, especially humans, and their use as an intermediate or for the preparation of pharmaceutical preparations for use in diagnostic methods or, preferably, for the therapeutic treatment of warm-blooded animals, especially humans.

2012/06/12 2011/01/14 Mutz; Michael Novartis AG; Novartis

Pharma GmbH

46

4-methyl-N-[3-(4-methyl-imidazol-1-yl)-5-trifluoromethyl-phenyl]-3-(4-pyr- idin-3-yl-pyrimidin-2-ylamino)-benzamide free base and salts thereof are prepared by various processes.

2013/01/01 2006/07/18

Manley; Paul W; Shieh; Wen-Chung; Sutton;

Paul Allen; Karpinski; Piotr "Peter" H; Wu;

Raeann; Monnier; Stephanie M.; Brozio; Jorg

Novartis AG; Novartis -3-(4-pyridin-3-yl-pyrimidin-2-ylamino)-benzamide are prepared by various processes.

2013/03/05 2012/03/13

Manley; Paul W; Shieh; Wen-Chung; Sutton;

Paul Allen; Karpinski; Piotr H; Wu; Raeann;

Monnier; Stephanie; Brozio; Jorg 4-methyl-N-[3-(4-methyl-imidazol-1-yl)-5-trifluoromethyl-phenyl]-3-(4-pyr- idin-3-yl-pyrimidin-2-ylamino)-benzamide free base and salts thereof are prepared by various processes.

2013/04/09 2012/08/03

Manley; Paul W; Shieh; Wen-Chung; Sutton;

Paul Allen; Karpinski; Piotr "Peter" H; Wu;

Raeann R; Monnier; Stephanie M; Brozio; Jorg

Novartis AG

US8507515 Crystalline form G of imatinib mesylate

Crystalline forms of imatinib mesylate (F, G, H, I and K) and their respective

characterization are disclosed. 2013/08/13 2011/07/15 Mutz; Michael Novartis AG

US8513256

Salt forms of 4-(4-methylpiperazin- 1-ylmethyl)-N-[4-methyl-3-(4-pyridin-3-yl)pyrimidin-- 2-ylamino)phenyl]-benzamide

The present invention relates to acid addition salts of 4-[(4-methyl-1-piperazinyl)methyl]-N-[4-methyl-3-[[4-(3-pyridinyl)-2-pyri- midinyl]amino]phenyl]-benzamide, which are selected from the group consisting of a tartrate salt, such as a (D)(-) tartrate salt or a (L)(+) tartrate salt, a hydrochloride salt, a citrate salt, a malate salt, a fumarate salt, a succinate salt, a benzoate salt, a benzenesulfonate salt, a pamoate salt, a formate salt, a malonate salt, a 1,5-naphthalenedisulfonate salt, a salicylate salt, a

cyclohexanesulfamate salt, a lactate salt, a mandelate salt, aq glutarate salt, an adipate salt, a squarate salt, a vanillate salt, an oxaloacetate salt, an ascorbate salt and a sulfate salt.

2013/08/20 2012/02/08 Burger; Hans Michael; Manley; Paul William;

Mutz; Michael Novartis AG -3-(4-pyridin-3-yl-pyrimidin-2-ylamino)-benzamide are prepared by various processes.

2013/11/12 2013/01/22

Manley; Paul W; Shieh; Wen-Chung; Sutton;

Paul Allen; Karpinski; Piotr H; Wu; Raeann;

Monnier; Stephanie; Brozio; Jorg

Novartis AG

US8592440 Crystalline form I of imatinib mesylate

Crystalline forms of imatinib mesylate (F, G, H, I and K) and their respective

characterizations are disclosed. 2013/11/26 2011/07/15 Mutz; Michael Novartis AG

47 Source: Compiled by this study

US8604045

Pyrimidylaminobenzamide derivatives for treatment of neurofibromatosis

The present invention relates to the use of pyrimidylaminobenzamide derivatives for the preparation of a drug for the treatment of non-cancerous, benign brain tumors, especially for the curative and/or prophylactic treatment of NF, and to a method of treating non-cancerous, benign brain tumors, especially for the curative and/or prophylactic treatment of NF.

2013/12/10 2012/12/05 Manley; Paul W. Novartis AG

US8633213 Crystalline form F of imatinib mesylate

Crystalline forms of imatinib mesylate (F, G, H, I and K) and their respective characterization are disclosed.

2014/01/21 2012/05/15 Mutz; Michael Novartis AG

US8653093

Combination of pyrimidylaminobenzamide compounds and imatinib for treating or preventing proliferative diseases

The invention provides a pharmaceutical combination comprising: a) a

pyrimidylaminobenzamide compound, and b) imatinib. and a method for treating or preventing a proliferative disease, especially GIST, using such a combination.

2014/02/18 2010/04/02 Alland; Leila; Manley; Paul W; Mestan;

Juergen Novartis AG

US8673930 Pyrimidylaminobenzamide derivatives for systemic mastocytosis

The present invention relates to the use of pyrimidylaminobenzamide derivatives for the preparation of a drug for the treatment of systemic mastocytosis.

2014/03/18 2010/04/29 Alland; Leila; Fabbro; Doriano; Mestan;

Jurgen; Manley; Paul W Novartis AG

US8697702

Method of optimizing the treatment of Philadelphia-positive leukemia with imatinib mesylate

The present invention relates to a method of treating Philadelphia-positive leukemia (Ph+

leukemia), in a particular chronic myeloid leukemia (CML), in a human patient population. More specifically, the present invention pertains to a method of treating Ph+

leukemia, such as CML or Phi+ ALL, in a human patient suffering from Ph+ leukemia comprising the steps of (a) administering a predetermined fixed amount of Imatinib as a free base or in the form of a pharmaceutically acceptable salt thereof to the human patient, (b) collecting at least one blood sample from the patient, e.g. within the first 12 months of treatment, (c) determining the plasma trough level (Cmin) of Imatinib, (d) determining the OCT-1 Activity in the blood sample, and (e) adjusting the dose of Imatinib applied to the individual patient in a manner that an Imatinib Cmin value is achieved in the patient of at least 800 ng/mL, if in step (c) an Imatinib Cmin value of less than 800 ng/mL is found and in step (d) an OCT-1 Activity is found below 6.0 to 10.0 ng/200,000 cells.

2014/04/15 2009/11/30 Wang; Yanfeng; Kalebic; Thea; Hughes;

2014/04/15 2009/11/30 Wang; Yanfeng; Kalebic; Thea; Hughes;