C."D
`
`(7;:;
`
`U.S. UTILIT PATENT APPLICATION
`PATENT DATE
`I I R 2 620
`
`S pLL4
`
`SCANNED
`
`0 I.P.E.
`fZI:.A. ~L
`
`SECTOR
`
`CLASS
`
`SUB ICLASS
`
`ART UNIT
`
`EXAMINER
`
`FILEDAITH:
`
`/
`
`FICHE
`r- DISK (CRF)
`r
`(Attached in pocket on right inside flap)
`
`PREPARED AND APPRdcVED FOR ISSUE
`
`ISSUING CL.PASIFICATION
`
`ORIGINAL
`
`CROSS REFERENCE(S)
`
`CLASS
`
`SUBCLASS
`
`CLASS
`
`SUBCLASS (ONE SUBCLASS PER BLOCK)
`
`INTERNATIONAL CLASSIFICATION
`I
`
`36
`
`c2
`__//o___
`
`,___
`
`_._
`
`L
`
`IEl
`
`continued on Issue Slip Inside File Jacket
`
`D TERMINAL
`DISCLAIMER
`
`She
`
`DRAWINGS
`Figs. D
`
`Print Fig.
`
`CLAIMS ALLOWED
`Total Claims
`Print Claim for O.G.
`
`E] a) The term of this patent
`subsequent to
`has been disclaimed.
`
`(date)
`
`rl b) The term of this patent shall
`not extend beyond the expiration date.
`of U.S Patent. No. _________PH__
`
`(Assistant Examiner)
`
`(Date)
`
`NOTICE OF ALLOWANCE MAILED
`
`pD Q o )\
`ISSUE FEE
`
`Amount Due
`
`Date Paid
`
`El c) The trminal _months of
`this patent have been disclaimed.
`.
`
`WARNING:
`The information disclosed herein may be
`Possession outside the U.S. Patent & T
`
`Form PTO-436A
`(Rev. 6/98)
`
`/-
`
`/V2.
`(Primary Examiner)
`
`j
`
`(LgalIntrument s Examiner)
`
`(Date)
`
`eISSU
`
`00
`0
`
`I
`
`<v
`E BATCH NUMBER
`
`stricted Unauthorized disclosure may be prohibited by the United States Code Title 35, Sections 122, 181 and 368.
`ti-rk OffIce is restricted to authorized employees and contractors only.
`em
`
`ISSUE FEE IN FILE
`
`...
`
`(LABEL AREA)
`
`(FACE
`
`Breckenridge Exhibit 1153
`Breckenridge v. Novartis IPR2017-01592
`Weckbecker Application
`Page 1
`
`

`

`6,362,164
`
`COMBINATION OF A SOMATOSTATIN ANALOGUE AND A
`RAPAMYCIN
`
`Transaction History
`
`
`Transaction Description
`Date
`12-07-1998 Initial Exam Team nn
`12-07-1998 Preliminary Amendment
`12-07-1998 Receipt of 371 Request
`12-14-1998 371 Application Preexamination Docketing
`12-15-1998 IB Paper Match
`01-20-1999 371 Application Preexamination Docketing
`01-20-1999 371 Application Preexamination Docketing
`05-03-1999 371 Application Preexamination Docketing
`05-04-1999 Released to OIPE
`05-05-1999 Notice of DO/EO Acceptance Mailed
`05-12-1999 Preliminary Amendment
`05-19-1999 Application Dispatched from OIPE
`05-19-1999 IFW Scan & PACR Auto Security Review
`06-03-1999 Case Docketed to Examiner in GAU
`12-23-1999 Case Docketed to Examiner in GAU
`02-14-2000 Mail Non-Final Rejection
`02-14-2000 Non-Final Rejection
`06-13-2000 Response after Non-Final Action
`06-22-2000 Date Forwarded to Examiner
`08-22-2000 Mail Non-Final Rejection
`08-22-2000 Non-Final Rejection
`01-25-2001 Response after Non-Final Action
`01-25-2001 Request for Extension of Time - Granted
`02-01-2001 Date Forwarded to Examiner
`04-03-2001 Final Rejection
`04-04-2001 Mail Final Rejection (PTOL - 326)
`07-05-2001 Response after Final Action
`07-11-2001 Date Forwarded to Examiner
`07-16-2001 Examiner Interview Summary Record (PTOL - 413)
`08-06-2001 Amendment/Argument after Notice of Appeal
`08-06-2001 Notice of Appeal Filed
`08-06-2001 Request for Extension of Time - Granted
`08-10-2001 Advisory Action (PTOL-303)
`08-13-2001 Mail Advisory Action (PTOL - 303)
`09-19-2001 Examiner Interview Summary Record (PTOL - 413)
`10-19-2001 Receipt into Pubs
`10-19-2001 Receipt into Pubs
`10-19-2001 Mail Notice of Allowance
`10-19-2001 Notice of Allowance Data Verification Completed
`11-02-2001 Workflow - File Sent to Contractor
`12-14-2001 Receipt into Pubs
`01-15-2002 Issue Fee Payment Verified
`01-15-2002 Issue Fee Payment Received
`02-18-2002 Application Is Considered Ready for Issue
`02-19-2002 Receipt into Pubs
`03-08-2002 Issue Notification Mailed
`03-26-2002 Recordation of Patent Grant Mailed
`03-26-2002 Patent Issue Date Used in PTA Calculation
`09-21-2005 Post Issue Communication - Certificate of Correction
` 
`
`Breckenridge Exhibit 1153
`Breckenridge v. Novartis IPR2017-01592
`Weckbecker Application
`Page 2
`
`

`

`PATNT AP-PLIC--ATION~
`
`09194957
`
`INITIALS _____
`
`CONTENTS
`Date receiv~d
`(Incl. C. of M.)
`or
`Date Mailed
`
`~~f~terecived
`~(Incl. C. of M.)
`or
`Date Mailed
`
`1. Application
`
`papers.,
`
`2.__
`
`09MY19933
`
`2.'
`
`3.
`
`6.
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`
`(LEFT OUTIDE
`
`Breckenridge Exhibit 1153
`Breckenridge v. Novartis IPR2017-01592
`Weckbecker Application
`Page 3
`
`

`

`ISSUE SLIP STAPLE AREA (for additional cross references)
`
`POSITION
`
`INmTALS
`
`i
`
`~D NO.
`ID NO.
`
`FEE DETERMINATION
`O.LP.E. CLASSIFIER
`FORMALITY REVIEW
`
`DATE
`DATE
`
`771
`
`INDEX OF CLAIMS
`N .
`................................. Rejected
`I
`=. ...............
`Allowed
`A
`(Through numeral)... Canceled
`0
`........ Restricted
`....................
`
`........
`Non-elected
`............................ Interference
`............
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`.............
`Objected
`
`Claim
`
`Date
`
`Claim
`
`Date
`
`0 1 1
`
`04
`
`106
`
`107
`108
`105
`109
`119
`
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`
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`115
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`93!
`941
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`96
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`
`91--------
`1 99
`
`If more than 150 claims or 10 actions
`staple additional -sheet here
`
`(LEFT INSIDE)
`
`-
`
`.
`
`Date
`
`Cla
`
`~
`20t
`CM
`
`cDV
`
`'
`
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`
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`37
`38
`39
`40
`41
`42
`43
`44
`45
`46
`47
`
`49
`50
`
`Breckenridge Exhibit 1153
`Breckenridge v. Novartis IPR2017-01592
`Weckbecker Application
`Page 4
`
`

`

`/
`
`/
`
`/
`
`/
`
`'V/
`
`(RIGHT OUTSIDE)
`
`Breckenridge Exhibit 1153
`Breckenridge v. Novartis IPR2017-01592
`Weckbecker Application
`Page 5
`
`

`

`04/02/01
`
`1. Borin
`
`AU
`CS
`
`SO
`
`PB
`DT
`LA
`AB
`
`CAPLUS COPYRIGHT 2001 ACS
`1997:37048 CAPLUS
`AN
`DN
`126:54378
`Paclitaxel combination therapy in the treatment of metastatic breast
`TI
`cancer
`Holmes, Frankie Ann
`The University of Texas M.D. Anderson Cancer Center, Houston, TX,
`77030-4009, USA
`Semin. Oncol. (1996), 23(5, Suppl. 12), 29-39
`CODEN: SOLGAV; ISSN: 0093-7754
`Saunders
`Journal; General Review
`English
`A review with 56 refs. After the single-agent activity of paclitaxel
`(Taxol; Bristol-Myers Squibb company, Princeton, NJ) was confirmed,
`trials
`to develop a synergistic combination began. Doxorubicin, the
`most active agent for breast cancer, was studied first. As paclitaxel
`became more available, other combinations, including high-dose regimens
`and adjuvant therapies, have been studied. No optimal combination
`regimen
`has been defined. Recent and/or ongoing trials are looking at paclitaxel
`in combination with cisplatin, cyclophosphamide, 5-fluorouracil/folinic
`acid, and mitoxantrone combinations, as well as with high-dose regimens
`and as adjuvant therapy. This review describes a plethora of combination
`studies finally under way to better define the optimal use of paclitaxel
`in breast cancer therapies, both as adjuvant treatment and for metastatic
`disease. Because of the unpredictable nature of drug
`interactions related to schedule and sequence, ad hoc combinations should
`not be undertaken outside the context of a well-designed trial.
`
`Breckenridge Exhibit 1153
`Breckenridge v. Novartis IPR2017-01592
`Weckbecker Application
`Page 6
`
`

`

`04/02/01
`
`M. Borin
`
`CAPLUS COPYRIGHT 2001 ACS
`1990:512336 CAPLUS
`AN
`DN
`113:112336
`In vitro bactericidal activity of tobramycin and amikacin alone and in
`TI
`combination against isolates of Pseudomonas aeruginosa from patients with
`cystic fibrosis
`Bertrou, A.; Marty, N.; Henry, S.; Agueda, L.; Chabanon, G.
`Lab. Bacteriol.-Virol., CHU Rangueil, Toulouse, 31054, Fr.
`Pathol. Biol. (1990), 38(5), 366-75
`CODEN: PTBIAN; ISSN: 0031-3009
`Journal
`French
`The bactericidal kinetics on 60 P. aeruginosa isolates were studied by
`
`AU
`CS
`SO
`
`DT
`LA
`AB
`the
`
`liq. medium micromethod. Bacteria were incubated with tobramycin and
`amikacin alone at several concns. and combined with piperacillin,
`cefsulodin, ceftazidime, imipenem, and ciprofloxacin at concns. obtained
`in vivo. When used alone, tobramycin showed the most rapid bactericidal
`activity, whatever the concn. used. The bactericidal activity
`(.gtoreq.99.99% killing) was obtained in 5 h with I or 2 times. MIC
`against the majority of the strains with the 2 aminoglycosides. No
`difference was found between tobramycin and amikacin when combined with
`
`antibiotic which notably increases the bactericidal activity. The
`combination of amikacin plus imipenem was synergistic against
`48% of the strains; 26% were synergistically inhibited by amikacin plus
`ciprofloxacin. When correlated with susceptibility patterns, the results
`were rather unpredictable.
`
`an
`
`Breckenridge Exhibit 1153
`Breckenridge v. Novartis IPR2017-01592
`Weckbecker Application
`Page 7
`
`

`

`AN
`DN
`TI
`AU
`CS
`
`SO
`
`CY
`DT
`
`04/02/01
`
`M. Borin
`
`MEDLINE
`
`90140745
`90140745
`Design of combination biotherapy studies: future goals and challenges.
`Gilewski T A; Golomb H M
`Section of Hematology/Oncoiogy, University of Chicago Medical Center, IL
`60637..
`SEMINARS IN ONCOLOGY, (1990 Feb) 17 (1 Suppl I) 3-10; discussion 8-41.
`Ref: 83
`Journal code: UNS. ISSN: 0093-7754.
`United States
`Journal; Article; (JOURNAL ARTICLE)
`General Review; (REVIEW)
`(REVIEW, TUTORIAL)
`English
`LA
`Priority Journals; Cancer Journals
`FS
`199005
`EM
`The recent large-scale production of biomodulators, also known as
`AB
`biologic
`response modifiers, made possible through recombinant DNA technology,
`offers the potential for significant advances in the treatment of cancer.
`The antitumor activity of these agents, such as interferons,
`interleukins,
`and tumor necrosis factor, have generated enthusiasm for further
`investigation. In an effort to improve response rates, combinations of
`these agents both with and without conventional therapies are currently
`being examined. Clinical trials have been conducted with various
`therapeutic combinations, including a biomodulator plus chemotherapy,
`combinations of different biomodulators, a biomodulator with concomitant
`chemotherapy and radiation, and multiple combinations of chemotherapies
`and biomodulators. These approaches are promising and some limited
`successes have been reported; however, the goal of increased anticancer
`activity without greater toxicities or antagonism between various agents
`is not always achieved. Synergism among active agents is not
`necessarily assured and quite unexpected and unpredictable
`toxicities have been noted. The studies to date suggest that important
`
`new
`
`therapies will emerge, but many questions have to be answered before the
`specific roles of these new treatments are defined.
`
`Breckenridge Exhibit 1153
`Breckenridge v. Novartis IPR2017-01592
`Weckbecker Application
`Page 8
`
`

`

`04/02/01
`
`M. Borin
`
`(FILE 'CAPLUS' ENTERED AT 10:54:01 ON 03 APR 2001)
`58245 S SYNERGI#,###
`18 S L3 AND UNPREDICTAB?
`
`FILE 'MEDLINE, BIOSIS, EMBASE' ENTERED AT 11:01:25 ON 03 APR 2001
`42 FILE MEDLINE
`13 FILE BIOSIS
`24 FILE EMBASE
`TOTAL FOR ALL FILES
`79 S L3 AND UNPREDICTAB?
`0 FILE MEDLINE
`0 FILE BIOSIS
`0 FILE EMBASE
`TOTAL FOR ALL FILES
`0 S L8 NOT L4
`52 DUPLICATE REMOVE L8 (27 DUPLICATES REMOVED)
`42 S L13
`11 FILE MEDLINE
`3 S L13
`0 FILE BIOSIS
`7 S LI3
`0 FILE EMBASE
`TOTAL FOR ALL FILES
`11 S L13 AND REVIEW/DT
`250 FILE MEDLINE
`134 FILE BIOSIS
`145 FILE EMBASE
`TOTAL FOR ALL FILES
`529 S SYNERGI? AND SOMATOSTATIN?
`0 FILE MEDLINE
`0 FILE BIOSIS
`0 FILE EMBASE
`TOTAL FOR ALL FILES
`0 S L24 AND RAPAM?
`0 FILE MEDLINE
`0 FILE BIOSIS
`0 FILE EMBASE
`TOTAL FOR ALL FILES
`0 S L24 AND UNPREDICT?
`23 FILE MEDLINE
`0 FILE BIOSIS
`0 FILE EMBASE
`TOTAL FOR ALL FILES
`23 S L24 AND REVIEW/DT
`
`L3
`L4
`
`L5
`L6
`L7
`
`L8
`L9
`LI0
`LlI
`
`L12
`L13
`L14
`LIS
`L16
`L17
`L18
`L19
`
`L20
`L21
`L22
`L23
`
`L24
`L25
`L26
`L27
`
`L28
`L29
`L30
`L31
`
`L32
`L33
`L34
`L35
`
`L36
`
`Breckenridge Exhibit 1153
`Breckenridge v. Novartis IPR2017-01592
`Weckbecker Application
`Page 9
`
`

`

`04/02/01
`
`M. Borin
`
`(FILE 'CAPLUS' ENTERED AT 10:54:01 ON 03 APR 2001)
`58245 S SYNERGI####
`18 S L3 AND UNPREDICTAB?
`
`L3
`L4
`
`=> d bib, abs 4,7,9,11,13,17
`
`L4
`AN
`DN
`TI
`
`AU
`CS
`
`SO
`
`PB
`DT
`LA
`AB
`
`ANSWER 4 OF 18 CAPLUS COPYRIGHT 2001 ACS
`1997:37048 CAPLUS
`126:54378
`Paclitaxel combination therapy in the treatment of metastatic breast
`cancer
`Holmes, Frankie Ann
`The University of Texas M.D. Anderson Cancer Center, Houston, TX,
`77030-4009, USA
`Semin. Oncol. (1996), 23(5, Suppl. 12), 29-39
`CODEN: SOLGAV; ISSN: 0093-7754
`Saunders
`Journal; General Review
`English
`A review with 56 refs. After the single-agent activity of paclitaxel
`(Taxol; Bristol-Myers Squibb Company, Princeton, NJ) was confirmed,
`trials
`to develop a synergistic combination began. Doxorubicin, the
`most active agent for breast cancer, was studied first. As paclitaxel
`became more available, other combinations, including high-dose regimens
`and adjuvant therapies, have been studied. No optimal combination
`regimen
`has been defined. Recent and/or ongoing trials are looking at paclitaxel
`in combination with cisplatin, cyclophosphamide, 5-fluorouracil/folinic
`acid, and mitoxantrone combinations, as well as with high-dose regimens
`and as adjuvant therapy. This review describes a plethora of combination
`studies finally under way to better define the optimal use of paclitaxel
`in breast cancer therapies, both as adjuvant treatment and for metastatic
`disease. Because of the unpredictable nature of drug
`interactions related to schedule and sequence, ad hoc combinations should
`not be undertaken outside the context of a well-designed trial.
`
`L4
`AN
`DN
`TI
`
`AU
`CS
`SO
`
`DT
`LA
`AB
`
`ANSWER 7 OF 18 CAPLUS COPYRIGHT 2001 ACS
`1994:153032 CAPLUS
`120:153032
`Synergistic effects of monensin in combination with permethrin
`or neomycin on neuronal activity
`Nation, Patrick N; Roth, Sheldon H
`Heritage Med. Res. Cent., Univ. Alberta, Edmonton, AB, T6G 2S2, Can.
`Vet. Hum. Toxicol. (1993), 35(5), 414-8
`CODEN: VHTODE; ISSN: 0145-6296
`Journal
`English
`Drug combinations have the potential to produce novel and
`unpredictable responses on nervous tissue. This study was
`designed to test the hypothesis that the effects of combinations of
`monensin (an ionophore antibiotic) and either neomycin (an aminoglycoside
`antibiotic) or permethrin (synthetic pyrethroid) are synergistic
`Effects of the drug combinations upon the elec. properties and
`
`membra ne
`
`Breckenridge Exhibit 1153
`Breckenridge v. Novartis IPR2017-01592
`Weckbecker Application
`Page 10
`
`

`

`L4
`AN
`DN
`TI
`
`AU
`CS
`SO
`
`DT
`LA
`AB
`the
`
`an
`
`L4
`AN
`DN
`TI
`
`AU
`CS
`SO
`
`DT
`LA
`AB
`
`activities of an in vitro sensory neuron prepn. were found to be greater
`than expected from addn. of the effects of the same drugs acting
`individually, ind' ting synergism and thus suppor
`g the
`hypothesis. It wa- concluded that drugs acting at -. fferent neuronal
`membrane sites and applied in combination produce unpredictable
`responses. Such drug combinations behave as if they were novel drugs.
`
`ANSWER 9 OF 18 CAPLUS COPYRIGHT 2001 ACS
`1990:512336 CAPLUS
`113:112336
`In vitro bactericidal activity of tobramycin and amikacin alone and in
`combination against isolates of Pseudomonas aeruginosa from patients with
`cystic fibrosis
`Bertrou, A.; Marty, N.; Henry, S.; Agueda, L.; Chabanon, G.
`Lab. Bacteriol.-Virol., CHU Rangueil, Toulouse, 31054, Fr.
`Pathol. Biol. (1990), 38(5), 366-75
`CODEN: PTBIAN; ISSN: 0031-3009
`Journal
`French
`The bactericidal kinetics on 60 P. aeruginosa isolates were studied by
`
`liq. medium micromethod. Bacteria were incubated with tobramycin and
`amikacin alone at several concns. and combined with piperacillin,
`cefsulodin, ceftazidime, imipenem, and ciprofloxacin at concns, obtained
`in vivo. When used alone, tobramycin showed the most rapid bactericidal
`activity, whatever the concn. used. The bactericidal activity
`(.gtoreq.99.99% killing) was obtained in 5 h with I or 2 times. MIC
`against the majority of the strains with the 2 aminoglycosides. No
`difference was found between tobramycin and amikacin when combined with
`
`antibiotic which notably increases the bactericidal activity. The
`combination of amikacin plus imipenem was synergistic against
`48% of the strains; 26% were synergistically inhibited by amikacin plus
`ciprofloxacin. When correlated with susceptibility patterns, the results
`were rather unpredictable.
`
`ANSWER i OF 18 CAPLUS COPYRIGHT 2001 ACS
`1985:3110 CAPLUS
`102:3110
`Unpredictable interactions between cefotetan and penicillins or
`aminoglycosides
`Barry, A. L.; Packer, R. R.; Jones, R. N.
`Clin. Microbiol. Inst., Tualatin, OR, 97062, USA
`Diagn. Microbiol. Infect. Dis. (1984), 2(4), 347-51
`CODEN: DNIDDZ; ISSN: 0732-8893
`Journal
`English
`The bacteriostatic and bactericidal activity of gentamicin, amikacin,
`piperacillin, azlocillin, ampicillin, benzylpenicillin, and oxacillin
`against 85 selected isolates was measured alone and in the presence of
`subinhibitory concns. of cefotetan. A potential for antagonistic
`interactions between cefotetan and acylamino penicillins (piperacillin >
`azlocillin > ampicillin) were obsd. with some strains; synergy was
`suggested with other isolates, however. Bacteriostatic and bactericidal
`activity of the 2 aminoglycosides was enhanced by cefotetan with most
`gram-neg. bacilli, but bactericidal activity was significantly diminished
`with 4 of 65 strains. Piperacillin and cefotetan were clearly
`antagonistic with 11 of 44 strains and synergistic with 4 of 44
`strains of gram-neg. bacilli: the remaining 21 strains gave off scale end
`points and could not be analyzed in that way.
`
`L4
`AN
`DN
`TI
`
`ANSWER 13 OF 18 CAPLUS COPYRIGHT 2001 ACS
`1983:591500 CAPLUS
`99:191500
`In vitro study of the combination of rifampin with oxacillin against
`
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`
`

`

`Staphylococcus aureus
`Van der Auwera, P.; Klastersky J.
`Inst. Jules Borde' Univ. Bruxelles, Brussels, Bel(
`Rev. Infect. Dis. ,983), 5(Suppl. 3), S509-14
`CODEN: RINDDG; ISSN: 0162-0886
`Journal
`English
`The interaction of rifampin and oxacillin in various concns. was examd.
`
`AU
`CS
`SO
`
`DT
`LA
`AB
`in
`
`vitro by a dynamic biophotometric technique. While synergism
`was obsd. occasionally, most concns. studied exhibited either antagonism
`or indifference. No antagonism was obsd. with rifampin-resistant
`strains.
`Rifampin-resistant strains often emerged when the drug was tested alone.
`These findings again illustrate the complex and often
`unpredictable effect of combining rifampin with .beta.-lactam
`antibiotics.
`
`DT
`LA
`AB
`
`L4
`AN
`DN
`TI
`AU
`CS
`SO
`
`ANSWER 17 OF 18 CAPLUS COPYRIGHT 2001 ACS
`1972:413925 CAPLUS
`77:13925
`Interaction of drugs inhibiting different steps in the synthesis of DNA
`Grindey, Gerald B.; Nichol, Charles A.
`Dep. Exp. Ther., Roswell Park Mem. Inst., Buffalo, N. Y., USA
`Cancer Res. (1972), 32(3), 527-31
`CODEN: CNREA8
`Journal
`English
`In leukemia L1210 suspension cultures, combinations of
`1-.beta.-D-arabinofuranosylcytosine (ara-C) [147-94-4] with either
`methotrexate (I) [59-05-2] or 5-fluorodeoxvuridine (FUdR) [50-91-9]
`showed
`strong antagonistic effects compared to their independent inhibitions of
`DNA synthesis. Combination of 1-formylisoquinoline thiosemicarbazone
`(IQ-i) [2365-26-6] with I yielded slight antagonism, while the
`combination
`of IQ-I with FUdR was additive or slightly synergistic. The
`combination of 9-.beta.-D-arabinofuranosyladenine [5536-17-4] with I was
`antagonistic, whereas the combination of 9-.beta.-D-
`arabinofuranosyladenine with FUdR was additive. Also, the combination of
`9-.beta.-D-arabinofuranosyladenine with either IQ-I or ara-C was
`additive.
`The primary site of action of ara-C in these growing cells is not
`inhibition of ribonucleotide reductase [9040-57-7]. The various
`interactions obsd. in this study were unpredictable and could
`not be explained by the present concepts concerning combination
`chemotherapy.
`
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`

`

`11/02/99
`
`M. BORIN
`
`Page1
`
`Trying 3106000224.. .Open
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`FILE 'HOME' ENTERED AT 09:47:47 ON 11 NOV 1999
`
`=> file caplus
`
`COST IN U.S. DOLLARS
`
`FULL ESTIMLTED COST
`
`SINCE FILE
`ENTRY
`0.15
`
`TOTAL
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`

`FILE 'CAPLUS' ENTERED AT 09:47:57 ON 11 NOV 1999
`USE IS SUBJECT TO THE TEP MIS OF YOUR STN CUSTOMER AGREEMENT.
`3" FOR DETAILS.
`PLEASE SEE "HELP USAGET
`COPYRIGHT (C) 1999 AMERIeN CHEMICAL SOCIETY (ACS)
`
`Copyright of the articles to which records in this database refer is
`held by the publishers listed in the PUBLISHER (PB) field (available
`for records published or updated in Chemical Abstracts after December
`26, 1996), unless otherwise indicated in the original publications.
`
`FILE COVERS 1967 - 11 Nov 1999 VOL 131 ISS 20
`FILE LAST UPDATED: 10 Nov 1999 (19991110/ED)
`
`This file contains CAS Registry Numbers for easy and accurate
`substance identification.
`
`This file supports REGIstRY for direct browsing and searching of
`all substance data from the REGISTRY file. Enter HELP FIRST for
`more information.
`
`=> s ?rapamycin or (lactam macrolide)
`
`1746 ?RAPAMYCIN
`19304 LACTAM
`11444 LACTAMS
`23695 LACTAM
`(LACTA OR LACTAMS)
`5282 MACROLIDE
`2678 MACROLIDES
`6274 MACROLIDE
`(MACROLIDE OR MACROLIDES)
`24 LACTAN MACROLIDE
`(LACTAM (W) MACROLIDE)
`1770 ?RAPANYCIN OR (LACTA MACROLIDE)
`
`L1
`
`=> s somatostatin or ostreotide or vapreotide or lanreotide
`
`14445 SOMATOSTATIN
`119 SOMATOSTATINS
`14451 SOMATOSTATIN
`(SOMATOSTATIN OR SOMATOSTATINS)
`0 OSTREOTIDE
`26 VAPREOTIDE
`88 LANREOTIDE
`14466 SOMATOSTATIN OR OSTREOTIDE OR VAPREOTIDE OR LANREOTIDE
`
`L2
`
`:> del 12
`
`DELETE L2? iY)/N:v
`
`=> s scmatostatin or octreotide or vapreotide or lanreotide
`
`14445 SOMATOSTATIN
`119 SOMATOSTATINS
`14451 SOMATOSTATIN
`(SOMATOSTATIN OR SOMATOSTATINS)
`1053 OCTREOTIDE
`5 OCTREOTIDES
`1053 OCTREOTIDE
`(OCTRECTIDE OR OCTREOTIDES)
`
`09194957
`
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`
`

`

`26 VAPREOTIDE
`88 LANREOTIDP-
`14749 SOMATOST
`
`L2
`
`z>
`
`s 12 and 11
`
`3 L2 AND LI
`
`d bib, kwic 1-3
`
`N OR OCTREOTIDE OR VAPREOTIDE
`
`LANREOTIDE
`
`L3
`AN
`DN
`TI
`
`IN
`PA
`SO
`
`ANSWER 1 OF 3 CAPLUS COPYRIGHT 1999 ACS
`1998:13858 CAPLUS
`128:84386
`Combination of a somatostatin analog and a rapamycin
`for the prevention or treatment of cell hyperproliferation
`Weckbecker, Gisbert
`Novartis A.-G., Switz.; Weckbecker, Gisbert
`PCT Int. Appl., 31 pp.
`CODEN: PIXXD2
`Patent
`DT
`English
`LA
`FPN.CNT 1
`PATENT NO.
`
`KIND DATE
`
`A PPLICATION NO. DATE
`
`A !
`19971218
`AT, AU, AZ, BA,
`ES, FI, GB, GE,
`LR, LS, LT, LU,
`RU, SD, SE, SG,
`ZW, AM, AZ, BY,
`LS, MW, SD, SZ,
`IE, IT, LU, MC,
`MR, NE, SN, TD,
`19971218
`AA
`Al
`19980107
`19990217
`Al
`CH, DE, DK, ES,
`19960611
`19960916
`19970611
`
`PT
`
`OS
`TI
`
`AB
`
`ST
`
`IT
`
`IT
`
`IT
`
`WO 9747317
`W: AL, AM,
`DK, EE,
`LC, LK,
`PT, RO,
`VN, YU,
`RW: GH, KE,
`GB, GR,
`GN, ML,
`CA 2249439
`AU 9732572
`EP 896544
`R: AT, BE,
`PRAI GB 1996-12171
`GB 1996-19310
`WO 1997-EP3036
`MARPAT 128:84386
`Combination of a somatostatin analog and a rapamycin
`for the prevention or treatment of cell hyperproliferation
`A combination of a compd. of the somatostatin class (e.g.
`octreotide) and a rapamycin macrolide is useful for the
`prevention or treatment of cell hyperproliferation. The combination is
`synergistic.
`somatostatin analog rapamycin macrolide combination
`antiproliferative; hyperproliferation somatostatin analog
`rapamycin synergistic combination; octreotide
`rapamycin macrolide antiproliferative
`Pancreatic tumors
`(inhibitors; somatostatin analog-rapamycin
`macrolide combination for prevention or treatment of cell
`hyperproliferation)
`Injections (drug delivery systems)
`Solutions (drug delivery systems)
`(injection soins.; somatostatin analog-rapamycin
`macrolide combination for prevention or treatment of cell
`hyperproliferation)
`Antitumor agents
`(pancreatic; somatostatin analog-raparmycin
`
`19970611
`WO 1997-EP3036
`BG, BR, BY, CA, CH, CN, CU, CZ, DE,
`HU, IL, IS, JP, KE, KG, KP, KR, KZ,
`MD, MG, MK, MN, MW, MX, NO, NZ, PL,
`SK, TJ, TM, TR, TT, UA, UG, US, UZ,
`KZ, MD, RU, TJ, TM
`ZW, AT, BE, CH, DE, DK, ES, FI, FR,
`PT, SE, BF, BJ, CF, CG, CI, CM, GA,
`
`CA 1997-2249439 199706-L
`19970611
`AU 1997-32572
`19970611
`EP 1 997-928175
`FR, GB, GR, IT, LI, LU, NL, SE,
`
`PT, IE, FI
`
`09194957
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`
`

`

`IT
`
`IT
`
`IT
`
`L3
`AN
`DN
`TI
`
`AU
`
`CS
`SO
`
`DT
`LA
`AB
`
`macrolide combination for prevention or treatment of cell
`hyperproliferat,'-n)
`Amppuls
`Antiproliferative agents
`Antitumor agents
`Capsules (drug delivery systems)
`Drug delivery systems
`Sustained release drug delivery systems
`Synergistic drug interactions
`(somatostatin analog-rapamycin macrolide
`combination for prevention or treatment of cell hyperproliferation)
`Macrolides
`RL. BAC (Biological activity or effector, except adverse); THU
`(Therapeutic use); BIOL (Biological study); USES (Uses)
`(somatostatin analog-rapamycin macrolide
`combination for prevention or treatment of cell hyperproliferation)
`51110-01-1D, Somatostatin, analogs
`53123-88-9,
`Rapamycin
`53123-88-9D, Rapamycin, derivs.
`83150-76-9, Octreotide
`103222-11-3, Vapreotide
`108736-35-2, Lanreotide
`135467-16-2, Octreotide
`pamoate
`159351-69-6
`RL: BAC (Biological activity or effector, except adverse); THU
`(Therapeutic use); BIOL (Biological study); USES (Uses)
`(somatostatin analog-rapamycin macrolide
`combination for prevention or treatment of cell hyperproliferation)
`
`ANSWER 2 OF 3 CAPLUS COPYRIGHT 1999 ACS
`1993:573820 CAPLUS
`119:173820
`Inhibition of cAMP-responsive element-mediated gene transcription by
`cyclosporin A and FK506 after membrane depolarization
`Schwaninger, Markus; Blume, Roland; Oetjen, Elke; Lux, Gundula; Knepel,
`Willhart
`Cent. Pharmacol. Toxicol., Univ. Goettingen, Goettingen, 37070, Germany
`J. Biol. Chem. (1993), 268(31), 23111-15
`CODEN: JBCHA3; ISSN: 0021-9258
`Journal
`English
`than CsA. CsA/FK506 responsiveness was mediated by the glucagon
`.
`.
`.
`CRE and also by well characterized CREs of the choriogonadotropin and
`somatostatin gene. Rapamycin antagonized the inhibitory
`effect of FK506 but not CsA, suggesting that FK506 and CsA may act through
`complex formation with.
`
`L3
`AN
`DN
`TI
`
`iN
`PA
`SO
`
`ANSWER 3 OF 3 CAPLUS COPYRIGHT 1999 ACS
`1992:99301 CAPLUS
`116:99301
`Maleic anhydride copolymers as antidotes for the cytotoaxicity of neoplasm
`inhibitors
`Bach, Ardalan; Shanahan, William R., Jr.
`Searle, G. D., and Co., USA
`Eur. Pat. Appl., 27 pp.
`CODEN: EPXXDW
`DT
`Patent
`English
`LA
`FAN.CNT 1
`PATENT NO.
`
`KIND DATE
`
`APPLICATION NO. DATE
`
`PI
`
`EP 393575
`Al
`19901024
`EP 393575
`19940316
`B1
`R: AT, BE, CH, DE, DK, ES, FR, GB, GR, IT, LI, LU, NL, SE
`CA 2014732
`AA
`19901017
`CA 1990-2014732 199 0 04 1 7
`JP 02292227
`A2
`19901203
`JP 1990-101530
`19900417
`
`EP 1990-107246
`
`19900417
`
`09194957
`
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`Weckbecker Application
`Page 16
`
`

`

`AT 1990-107246
`ES 1990-107246
`
`19900417
`19900417
`
`19940415
`E
`19941216
`T-
`0417
`1
`19ru0417
`
`AT 102838
`ES 2062155
`PRAi US 1989-339503
`EP 1990-107246
`MARPAT 116:99301
`50-91-9, Floxuridine
`50-76-0, Dactinomycin
`50-18-0, Cyclophosphamide
`53-19-0,
`51-21-8D, conjugates with fibrinogens
`51-21-8, 5-Fluorouracil
`57-22-7
`56-18-8, Norspermidine
`54-42-2, NSC 39661
`Mitotane
`113-15--5,
`75-19-4D, Cyclopropane, spiro derivs.
`59-05-2, Methotrexate
`147-94-4,
`127-07-1 - 143-67-9, Vinblastine sulfate
`ERgotamine
`154-42-7, Thioguanine
`147-94-4D, Cytarabine, conjugates
`Cytarabine
`305-03-3, Chlorambucil
`302-79-4, Retinoic acid
`154-93-8, Carmustine
`645-05-6,
`642-18-2
`636-65-7, Isoglutamine
`432-70-2, .alpha.-Carotene
`1404-00-8,
`1149-99-1, Illudin
`671-16-9, Procarbazine
`Altretamine
`1948-56-7D, Dehydroalanine, N--acyl
`1404-64-4, Sparsomycin
`Mitomycin
`3094-09-5,
`3073-59-4, NSC 95580
`2353-33-5, NSC 127716
`deriv.
`4005-S1-0, Aminothiadiazole
`3778-73--2, Ifosfamide
`Doxifluridine
`5373-42-2, Thaliblastine
`4759-48-2, Isotretinoin
`4342-03-4
`7440-06-4D, Platinum, derivs.,
`6829-55-6
`6620-60-6, Proglumide
`7534-61-4, NSC 145813
`7481-89-2, Dideoxycytidine
`complexes
`9014-02-2D, Neocarzinostatin, conjugates with styrene-maleci acid
`9041-93-4, Bleomycin sulfate
`9015-68-3, Asparaginase
`copolymer
`12633-27-1, T
`10318-26-0, Mitolactol
`9054-89-1, Superoxide dismutase
`13665-88-8,
`13494-90-1, Gallium nitrate
`13010-47-4, Lomustine
`680
`14459-29-ID, polymers
`13909-09-6, Semustine
`13909-02-9
`Mopidamol
`15663-27-1, Cisplatin
`15219-97-3, Oxalysine
`14930-96-2, Cytochalasin B
`21416-87-5,
`20830-81-3
`19624-67-0, SKF 101772
`18378-89-7, Plicamycin
`23214-92-8D,
`23214-92-8, Doxorubicin
`22862-76-6, Anisomycin
`Razoxane
`24584-09-6, ICRF 187
`25300-64-5D,
`conjugates with fibrinogens
`26833-87-4, Homoharringtonine
`conjugates with neocarzinostatin
`29767-20-2
`29069-24-7, Prednimustine
`27686-84-6, CHX 100
`33419-42-0
`33069-62-4
`31430-i8-9D, Nocodazole, N-acyl deriv.
`35144-64-CD, Aldophosphamide, analogs
`34140-52-6D, Aeroplysinin, derivs.
`40919-33-3,
`39544-74-6, Benzotript
`39389-47-4, Distamycin
`38077-12-2
`41992-23-8,
`41'729-52-6, Dezaguanine
`41575-94-4, Carboplatin
`Urdcytin
`51213-99-1, Clanfenur
`50264-69-2, Lonidamine
`Spi rogermanium
`52128-35-5,
`51350-19-7, EHNA
`51321-79-0, PALA
`51264-14-3, Amsacrine
`53123-88-9,
`52205-73-9, Estramustine phosphate sodium
`Trimetrexate
`53910-25-1, Pentostatin
`53643-48-4, Vindesine
`Rapamycin
`54526-94-2, Steffimycin B
`54350-48-0, Etretinate
`54083-22-6, Zorubicin
`55079--83-9, Acitretin
`55073-32-0, Genkwadaphnin
`54824-17-8, Mitonafide
`56420-45-2, Epirubicin
`56281-36-8, Motretinide
`55303-98-5, Avarol
`57576--44-0,
`56973-26-3, SM 108
`57248-88-1
`56605-16-4, Spiromustine
`58196-43-3
`58066-85-6, Hexadecylphosphocholine
`Aclarubicin
`58957-92-9
`58338-59-3, Dinaline
`58337-35-2, Elliptinium acetate
`59653-73-5, Teroxirone
`59040-30-1, Nafazatrom
`58994--96-0, Ranimustine
`61422-45-5,
`61251-97-6
`60784-46-5, Elmustine
`60084-10-8, Tiazofurin
`62488-57-7, NSC 26480
`62396-95-6
`61825-94-3, Oxaliplatin
`Carmofur
`63521-85-7, Esorubicin
`62928-11-4, Iproplatin
`62816-98-2, Tetraplatin
`6527