BOARD OF PATENT
`APPEALS &
`INTERFERENCES
`JUN II 1992
`
`IN THE UNI'l'ED S'l.'A!rES PA'.eEN'.r AND 'J!RADEMARK OFFICE
`BEFORE THE BOARD OF PATENT APPEALS AND INTERFERENCES
`
`v.
`
`PICARD ET AL
`v.
`
`FUJIKAWA RT AL
`
`INTERFERENCE 102,648
`EXAMINER-IN-CHIEF:
`MICHAEL SOFOCLEOUS
`
`:
`
`: . . . .
`: . • . •
`: . •
`
`DECLARATION--PATENTABLY DIS~INCT
`SUBJECT MM."l'ER
`
`HONORABLE COMMISSIONER OF PATENTS AND TRADEMARKS
`WASBING'l'ON, DC 20231
`.
`BOX INTERFERENCE
`
`SIR:
`
`!, MASAKI XITAHARA, do hereby declare and state that:
`
`I am a citizen and resident of Japan, and a named co(cid:173)
`1.
`inventor in u.s. Patent Application 07/233,752, involved in the
`above-captioned patent Interference.
`
`2. To demonstrate the unpredicted improvement in inhibition
`
`of cholesterol biosynthesis obtained when making specific election
`
`!
`
`•
`
`'..
`
`'.
`
`: ~- . ,_ --
`
`NCI Exhibit 2019
`Page 1 of 9
`
`
`APPEALS &
`INTERFERENCES
`JUN II 1992
`
`IN THE UNI'l'ED S'l.'A!rES PA'.eEN'.r AND 'J!RADEMARK OFFICE
`BEFORE THE BOARD OF PATENT APPEALS AND INTERFERENCES
`
`v.
`
`PICARD ET AL
`v.
`
`FUJIKAWA RT AL
`
`INTERFERENCE 102,648
`EXAMINER-IN-CHIEF:
`MICHAEL SOFOCLEOUS
`
`:
`
`: . . . .
`: . • . •
`: . •
`
`DECLARATION--PATENTABLY DIS~INCT
`SUBJECT MM."l'ER
`
`HONORABLE COMMISSIONER OF PATENTS AND TRADEMARKS
`WASBING'l'ON, DC 20231
`.
`BOX INTERFERENCE
`
`SIR:
`
`!, MASAKI XITAHARA, do hereby declare and state that:
`
`I am a citizen and resident of Japan, and a named co(cid:173)
`1.
`inventor in u.s. Patent Application 07/233,752, involved in the
`above-captioned patent Interference.
`
`2. To demonstrate the unpredicted improvement in inhibition
`
`of cholesterol biosynthesis obtained when making specific election
`
`!
`
`•
`
`'..
`
`'.
`
`: ~- . ,_ --
`
`NCI Exhibit 2019
`Page 1 of 9
`
`
`
`2
`
`for the substituents of the subject matter of the Count of the
`
`above Interference 1 the tests described below were conducted by me 1
`
`or under my direct supervision.
`
`3.
`
`'rests were conducted to determine the impact of specific
`
`substituents on compounds of the following formula:
`
`z
`
`wherein
`
`R' =
`H
`R3 = F
`R5 = cyclopropyl (c-Pr) and z is selected from the
`group consisting of
`
`NCI Exhibit 2019
`Page 2 of 9
`
`
`
`3 , ..
`
`(carpoxylic acid),
`
`-CH(OH)-CH2-CH(OH)-CH2-COOH
`-CH(OH)-CH2-CH(OH)-CH2-COONa
`(calciwn salt),
`-CH(OH)-CH2-CH(OH)-CH2COO!Ca
`-CH(OH)-CH2-CH(OH)-CH2COOR, wherein a is C1_3 alkyl and
`
`(sodiwn salt),
`
`HO
`
`(lactone)
`
`In compounds of the above
`
`fo:rmula, where as is cyclopropyl,
`
`unpredictably enhanced inhibition of cholesterol biosynthesis, as
`
`tested both in_ vitro and in vivo (culture cell) is obtained. This
`
`unexpected improvement is maintained even when contrasted with
`
`identical compounds save for. the identity of as, wherein Rs is
`
`isopropyl or n-propyl. This is true even if the identity of R5 is
`of larger si2e, such as a c6 substituent.
`
`4.
`
`In the test described above, inhibition of cholesterol
`
`·. ~-- .. ____ ._
`
`NCI Exhibit 2019
`Page 3 of 9
`
`
`
`4
`
`biosynthesis was determined according to two tests, A and B, as set
`forth in the specification of u.s. Patent Application 07/233,752,
`involved in the above-captioned Interference. These tests are set
`
`forth and identified as tests A and B · on pages 28-30 of the
`
`speci.fication.
`
`The results of the tests are set forth in the
`
`Tables attached to this Declaration.
`
`In the tables presented, the
`
`IC50 values are given, thus indicating higher activity in compounds
`giving lower IC50 values.
`
`5.
`
`The superior activity of co.mpounds bearing a R5
`
`cyclopropyl substituent could not, on the basis of my personal
`
`knowledge and experience, be predicted on the basis of chemical
`
`structure alone. There is nothing in the art that would lead one
`
`of skill, having the approximate level of a graduate chemist with
`
`several years of experience in the field, to conclude, on the basis
`
`of structural comparison alone, that the cyclopropyl substituent at
`
`R5 would confer superior activity in the inhiPition of cholesterol
`
`biosynthesis.
`
`I hereby declare that all statements made herein of.my own
`
`knowledge are true, and all statements made on information and
`
`belief are believed true. Further, I am aware that willful false
`
`._,. ...... ,_._
`
`NCI Exhibit 2019
`Page 4 of 9
`
`
`
`5
`
`statements and the like are punishable by fine, imprisonment or
`both, 18 u.s.c. §1001, and that such willful false statements may
`jeopardize the validity of u.s. Patent Application 07/233,752, any
`patent issued thereon, as well the rights of the party Fujikawa et
`
`al in the above-captioned Interference.
`
`DATE: ____ ~Ju~n~e~1~,~1~9~9~2 ________ __
`
`;MASAKI KI
`
`. . ,. ?,_;.
`
`NCI Exhibit 2019
`Page 5 of 9
`
`
`
`•: · ...
`
`(1) Test A:
`
`Inhibition of cholesterol biosynthesis from
`
`acetate in vitro
`
`This test was carried out as described on pages 28-29
`.
`of the specification. The numerical values indicate IC50
`(nanomolar concentration i.e. mol x lo-9 ).
`(a) Sodiutn salt
`
`carbon number
`
`l
`
`2
`
`3
`
`6
`
`Rs
`
`structure
`
`(b) Calcium salt
`
`carbon number
`
`ns
`
`structure
`
`normal
`
`iso
`cyclic
`
`1
`
`-
`
`X
`
`X
`
`2
`
`-
`
`X
`
`X
`
`3
`
`-
`
`23.0(i-Pr)
`
`4.4(c-Pr)
`
`normal
`
`71.0
`
`15.0
`
`93.l(n-Pt)
`
`>1000
`
`iso
`cyclic
`
`X
`
`X
`
`X
`
`X
`
`lO,O(i-Pr)
`
`4.2(c-Pr)
`
`-
`
`51
`
`6
`
`...
`
`-
`-
`
`NCI Exhibit 2019
`Page 6 of 9
`
`
`
`;z
`
`3
`
`6
`
`24.3
`
`·39,9(n-Pr)
`
`>1000
`
`I
`
`X
`
`X
`
`-
`2.8(c-Pr)
`
`-
`96
`
`6
`
`- --
`
`2
`
`-
`
`X
`
`X
`
`3
`
`-
`
`2S.9(i-l?r)
`
`6.8(c-Pr)
`
`(c) Ethyl eJ:Stel'"
`
`ca:t:bon number
`
`Rs
`
`structure
`
`normal
`
`iso
`
`cyclic
`
`(d) Lactone
`
`carbon number
`
`Rs
`
`structure
`
`normal
`
`iso
`cyclic
`
`1
`
`-
`
`X
`
`X
`
`1
`
`-
`
`X
`
`X
`
`X: Not existing
`
`-: Not t~sted
`
`NCI Exhibit 2019
`Page 7 of 9
`
`
`
`(:2) Test B:
`
`rnhibition of cholesterol biosvnthesis in
`
`culture cells
`
`This test was carried out as described on pages 29 to
`30 of the specification. The numerical values indieate IC50
`(nanomolar concentration i.e. ~ol x l0-9).
`(a) Sodium salt
`
`carbon number
`
`Rs
`
`structure
`
`normal
`
`iso
`
`cyclic
`
`(b) Calcium salt
`
`carbon number
`
`ns
`
`structure
`
`normal
`
`iso
`cyclic
`
`l
`
`-
`
`X
`
`X
`
`1
`
`-
`
`X
`
`X
`
`2
`
`3
`
`6
`
`1050
`
`· 733(n-Pr)
`
`>10000
`
`X
`
`X
`
`lOO(i-Pr}
`
`17,S(c-Pr)
`
`-
`
`394
`
`2
`
`.
`
`X
`
`X
`
`3
`
`-
`
`l05(i-Pr)
`3S.O(c-Pr)
`
`6
`
`-
`-
`-
`
`NCI Exhibit 2019
`Page 8 of 9
`
`
`
`{c) Ethyl ester
`
`c::~rbon number
`
`as
`
`structure
`
`normal
`
`iso
`cyclic
`
`1
`
`-
`
`X
`
`X
`
`2
`
`3
`
`6
`
`797
`
`SOl(n-l?r)
`
`>10000
`
`-
`
`39.l{c-Pr)
`
`X
`
`X
`
`-
`
`4000
`
`X: Not existing
`
`-: Not tested
`
`..
`
`.... ,,
`.... . . ,
`
`• ;711.
`
`··- :--..:.. -~· .
`
`. . -.
`
`'
`
`• l
`
`-.\••' ..
`
`. . . . : .....
`. ·:·· ·: '-..!!::'·
`·.
`. .....
`·~.
`
`"';
`
`•.
`
`....
`
`~ · .
`
`,. ..
`
`NCI Exhibit 2019
`Page 9 of 9
Accessing this document will incur an additional charge of $.
After purchase, you can access this document again without charge.
Accept $ Charge
Still Working On It
This document is taking longer than usual to download. This can happen if we need to contact the court directly to obtain the document and their servers are running slowly.
Give it another minute or two to complete, and then try the refresh button.
A few More Minutes ... Still Working
It can take up to 5 minutes for us to download a document if the court servers are running slowly.
Thank you for your continued patience.
This document could not be displayed.
We could not find this document within its docket. Please go back to the docket page and check the link. If that does not work, go back to the docket and refresh it to pull the newest information.
Your account does not support viewing this document.
You need a Paid Account to view this document. Click here to change your account type.
Your account does not support viewing this document.
Set your membership
status to view this document.
With a Docket Alarm membership, you'll
get a whole lot more, including:
- Up-to-date information for this case.
- Email alerts whenever there is an update.
- Full text search for other cases.
- Get email alerts whenever a new case matches your search.
One Moment Please
The filing “” is large (MB) and is being downloaded.
Please refresh this page in a few minutes to see if the filing has been downloaded. The filing will also be emailed to you when the download completes.
Your document is on its way!
If you do not receive the document in five minutes, contact support at support@docketalarm.com.
Sealed Document
We are unable to display this document, it may be under a court ordered seal.
If you have proper credentials to access the file, you may proceed directly to the court's system using your government issued username and password.
Access Government Site
