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Human Genome Sciences, Inc. v. Amgen, Inc. et al.

LETTER BRIEF REGARDING ISSUES ON APPEAL

EXHIBIT A

54113-0036/LEGAL13778157.1

Letter Brief Ex. A Order-Motion Times

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Filed by: Richard E. Schafer Administrative Patent Judge Mail Stop Interference P.O. Box 1450 Alexandria Va 223 13-1450 Tel: 571 -272-9797 Fax: 571 -273-0042

Paper 4
Filed: October 5,2005

UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE BOARD OF PATENT APPEALS AND INTERFERENCES (Administrative Patent Judge Richard E. Schafer) Human Genome Sciences, Inc., Junior Party (Application 101005,842-IFW Inventors: Jian Ni, Reiner L. Gentz, Guo-Liang Yu and Craig A. Rosen),

Immunex Corp., Senior Party (Patent 6,642,358 Inventors: Charles Rauch and Henning Walczak). Patent Interference No. 105,381 (RES) Order Preliminary Motion Times - Bd. R. 104(c) (Setting preliminary motion times) This order applies to motions, if any, authorized as the result of the conference call scheduled for November 21,2005 (Paper 1). 37 CFR fi 41. 121(a)(l) and (2). A. Time periods associated with motions The TIME PERIODS described below are set out in an Appendix to this ORDER. Action specified for each TIME PERIOD must be completed by the date specified for the TIME PERIOD. The parties are authorized to stipulatedifferent times (earlier or later, but not later than TIME PERIOD 7) for TIME PERIODS 1 through 6.' A notice of the stipulation must be promptly filed. The notice must be in the form of a photocopy of the Appendix attached to this ORDER with old

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In stipulating different times, the parties should consider the effect of the stipulation on times ( I ) to object to evidence (5 business days, Ed. R. 155(b)(l)), (2) to supplement evidence (10 business days, Ed. R. ISS(b)(2)), (3) to begin cross examination (noearlier than 2 1 days after service, SO 722.1.1) and (4) to conclude cross examination (at least 10 days before opposition or reply is due, SO 722.1.2).

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dates crossed out and new dates inserted by hand. The parties may not stipulate an extension of TIME PERIODS 7-8. 1. TIME PERIOD 1 a. File and serve all authorized motions and b. Serve but do not file evidence in support of these motions. If no party files a motion, the SENIOR PARTY must arrange a conference call with the parties and the Board so that appropriate adjustments to the schedule may be made. 2. TIME PERIOD 2 a. File and serve responsive motions (Bd. R. 12 1(a)(2)) in response to an opponent's motion filed during TIME PERIOD 1 and b. Serve but do not file evidence in support of these responsive motions. 3. TIME PERIOD 3 a. File and serve oppositions to all motions, including responsive motions and b. Serve but do not file evidence in support of these oppositions. 4. TIME PERIOD 4 a. File and serve replies to all oppositions and b. Serve but do not file evidence in support of these replies. 5. TIME PERIOD 5 a. File and serve any request for oral argument on motions, b. File and serve motions to exclude objected to evidence (Bd. R. 155(c); SO 7 21.3), and c. File and serve observations on cross examination (SO 7 22.7) of reply testimony. 6. TIME PERIOD 6 a. File and serve oppositions to an opponent's motion to exclude evidence and b. File and serve any response to observations.

7.

TIME PERIOD 7 File and serve replies to oppositions to motions to exclude evidence.

B. Deposition transcripts Transcripts of cross examinations and depositions taken under 35 U.S.C.
served, but not filed until the exhibits are filed.

5

24 must be

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C. Serving exhibits relied upon in motions An exhibit, including an affidavit, cited in connection with a motion, opposition, reply, or with affidavit, must be served, but not filedY2 the motion, opposition, reply or affidavit in which the exhibit is first mentioned. TIME PERIOD 8: Filing the record for decision on motions D. 1. File an original set of your exhibits and one working copy (or three copies if an oral argument is set) of your exhibits; 2. For each ofyour motions, file one folder (or three folders if an oral argument is set each) containing: a. The motion, b. Any corresponding opposition, c. Any corresponding reply, d. Any corresponding observations, and e. Any corresponding response to the observations. 3. File any ZIP@ 100 Mb disk or CD-ROM a party elects to file. E. Priority statements 1. At TIME PERIOD 1: a. File but do not serve a priority statement (Bd. R. 120; Bd. R. 204(a)). File and serve a notice advising each opponent of the filing of the b. priority statement. A junior party who does not file a priority statement shall not have access to 2. the priority statement of any other party. 3. Within one (1) week after TIME PERIOD 1, serve a copy of the priority statement upon each opponent (except for a junior party barred under T[ H.2 above).

/Richard E. Schaferl Administrative Patent Judge

Except when the Board sets an expedited schedule for a particular motion, in which case, all exhibits mentioned in that motion or the corresponding opposition or reply must be filed with the motion, opposition, reply, or affidavit in which the exhibit is first mentioned.

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cc (via overnight delivery): Attorney for Human Genome Sciences: STERNE, KESSLER, GOLDSTEIN & FOX P.L.L.C. 1100 New York Avenue, N.W. Washington, DC 20005 (202)37 1-2600 Attorney for Immunex: IMMUNEX CORPORATION Law Department 120 1 Amgen Court West Seattle, WA 98 119 (206)265-7000

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Appendix--ORDER - RULE 123(a) (Times for substantive motions; priority deferred) Interference 105,38 1(RES)
TIMEPERIOD1 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . January9,2006 File motions File (but serve one week later) priority statements TIMEPERIOD2 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . January30,2006 File responsive motions to motions filed in TIME PERIOD 1 TIMEPERIOD3 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . March13,2006 File oppositions to all motions TIME PERIOD 4 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . April 24,2006 File all replies TIMEPERIOD5 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . File request for oral argument File motions to exclude File observations TIME PERIOD 6 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . File oppositions to motions to exclude File response to observations

June 5,2006

June 26,2006

TIMEPERIOD7 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . July10,2006 File replies to oppositions to motions to exclude TIME PERIOD 8 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . File exhibits File sets of motions File any ZIP@ disks or CD-ROMs

. . . . July 17,2006

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Appendix 11--ORDER - RULE 123(a) (Times for substantive motions) Interference 105,381 (RES) Required Appendices 1. List of exhibits The list of exhibits cited in support of a motion, opposition, or reply, SO 77 13.3(b) & 14.3(a), must be set forth as an appendix to the motion, opposition, or reply, respectively. The appendix will not count against the page limit for the motion, SO 7 13.2, or opposition or reply, SO I.

7 14.2.
Statement of Material Facts The statement of proposed material facts for each motion, opposition, or reply must be set
2.

forth as an appendix to the motion, opposition, or reply, respectively. Bd.R. 121(d)(2). The appendix will not count against the page limit for the motion, SO 7 13.2, or opposition or reply, SO

7 14.2.

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Human Genome Sciences, Inc. v. Amgen, Inc. et al.

LETTER BRIEF REGARDING ISSUES ON APPEAL

EXHIBIT B

54113-0036/LEGAL13778157.1

Letter Brief Ex. B Order-Miscellaneous

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1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37

Paper 103 Filed: 9 April 2007 Mail Stop Interference P.O. Box 1450 Alexandria Va 22313-1450 Tel: 571-272-4683 Fax: 571-273-0042 UNITED STATES PATENT AND TRADEMARK OFFICE _______________ BEFORE THE BOARD OF PATENT APPEALS AND INTERFERENCES (Administrative Patent Judge Richard E. Schafer) _______________ Human Genome Sciences, Inc., Junior Party (Application 10/005,842-IFW Inventors: Jian Ni, Reiner L. Gentz, Guo-Liang Yu and Craig A. Rosen), v. Immunex Corp., Senior Party (Patent 6,642,358 Inventors: Charles Rauch and Henning Walczak). _______________ Patent Interference No. 105,381 (RES) _______________

Order - Miscellaneous - Bd.R. 104(a) A telephone conference call was held on April 3, 2007 at approximately 10:30 a.m., involving:
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1.

Jorge A. Goldstein, Esq. and Eldora Ellison, Esq., counsel for Human Genome Sciences (HGS),

2. 3.

Michael J. Wise, Esq., counsel for Immunex, and Richard E. Schafer, Administrative Patent Judge.

The conference call was requested by HGS. HGS requested permission to file a miscellaneous motion seeking additional discovery on the inventorship of its involved applications, permission to file a modified priority statement, to modify the priority schedule and/or to synchronize the times in this interference and Interference 105,380 with the times in Interference 105,361. The request to file a motion for additional discovery on HGS' inventorship was denied. The inventorship of HGS' involved applications is not at issue in these interferences. If HGS finds that it needs to change the inventorship of its applications, it may attempt to do so when its application returns to the jurisdiction of the Commissioner of Patents. For the purposes of these interferences, the inventor ship is as stated in HGS involved application. However, in order to provide HGS with an opportunity to further investigate the inventorship question, the schedule will be adjusted an additional month and is reset in the appendix to this order. The conference call to discuss the priority schedule set for April 26, 2007 at 4:00 p.m. is cancelled. The request to synchronize the times in this interference with the times in Interference 105,361 was also denied. HGS sought synchronization because of a concern that the opposing party in Interference 105,361 (Genentech) would be given an unfair advantage by having access to HGS' priority proofs. Interference 105,361 is currently awaiting a decision on substantive motions and has not entered the priority phase. Synchronizing the files would require suspending the priority schedule in these interferences. It was also suggested that Genentech be precluded from having access to HGS priority case. However, these interferences are open to the public and to preclude
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access by Genentech would require precluding public access to this interference. HGS also requests submitted an amended priority statement. This was also denied. However, HGS was authorized, as part of its priority case to submit proofs of an actual reduction to practice by March 25, 1997. Immunex raised a question relating the continuance of this interference into the priority phase in light of the fact that all of HGS' claims corresponding to the count in were held to be unpatentable. This matter is currently under consideration.

/Richard E. Schafer/ Administrative Patent Judge

cc (electronic filing): Counsel for HUMAN GENOME SCIENCES, INC. Jorge Goldstein, Esq. STERNE, KESSLER, GOLDSTEIN & FOX PLLC 1100 New York Avenue, N.W. Washington, D.C. 20005-3934 Tel: 202-371-2600 Email: [email protected]

Counsel for IMMUNEX CORP. Michael J. Wise, Esq. PERKINS COIE LLP 1620 26th Street 6th Floor, South Tower Santa Monica, CA 90404-4013 Tel: 310-788-3210 Email: [email protected]
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Appendix--ORDER - RULE 123(a) (Times for priority motions) Interference 105,381 (RES) TIME PERIOD 11.........................................................................................................July 6, 2007 Junior party only file priority motion and serve (but do not file) priority evidence TIME PERIOD 12.................................................................................................. August 17, 2007 Senior party only file priority motion and serve (but do not file) priority evidence TIME PERIOD 13............................................................................................September 28, 2007 File opposition to priority motions Serve (but do not file) opposition evidence TIME PERIOD 14.............................................................................................. November 9, 2007 File reply Serve (but do not file) reply evidence TIME PERIOD 15.............................................................................................December 21, 2007 Request oral argument File list of issues to be considered File observations File motion to exclude TIME PERIOD 16................................................................................................ January 11, 2008 File response to observations File opposition to motion to exclude TIME PERIOD 17................................................................................................ January 25, 2008 File reply to opposition to motion to exclude TIME PERIOD 18.............................................................................................. February 01, 2008 File and serve exhibits File sets of priority motions File CD-ROMs TIME PERIOD 19............................................................................................ Ferburary 29, 2008 Default oral argument date (if ordered) 1

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Human Genome Sciences, Inc. v. Amgen, Inc. et al.

LETTER BRIEF REGARDING ISSUES ON APPEAL

EXHIBIT C

54113-0036/LEGAL13778157.1

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The opinion in support of the decision being binding precedent of the Board. entered today is

Paper 101
By:

Trial S d o n Merits Panel Board of Patent Appeals and Interferences Mail Stop InterFerence P.O. Box 1450 Alexandria, VA 22313-1450 Tel: 571-272-9797 F a : 571-273-0042

Filed: March 26,2007

UNITED STATES PATENT AND TRADEMARK OFFICE

BEFORE THE BOARD OF PATENT APPEALS AND INTERFERENCES (Administrative Patent Judge Richard E. Schafer)

Human Genome Sdences, Inc. Junior Party (Application 10/0Q5,842-I FW Inventors: Jian Ni, Reiner L. Gentz, Guo-Liang Yu and Craig A. Rosen),

MAILED
MAR 2 6 2007
U WENTAND T S R A B O W OF rn APPEALS
A mBE N EdS Df C R
~ ~

lmmunex Corp., Senior Party (Patent 6,642,358 Inventors: Charles Rauch and Henning Walczak)
Patent Interference No. 105,381 (RES)

Before: SCHAFER, HANLON and SPIEGEL, Administrative Patent Judaes. SPIEGEL, Administrative Patent Judne.
DECISION MOTIONS Bd.R. 125(a)

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Interference No. 105,381 Human Genome Sciences, Inc. (Ni) v. tmmunex Corp. (Rauch)

1.

Introduction

This is a decision on the motions remaining in interference no. 105,381. Junior party Ni has filed four motions. Senior party Rauch has filed five motions. Ni substantive motion Ito substitute Ni proposed count 2 for current Count Iis denied. Ni substantive motion 2 for benefit for the purpose of priority is dismissed as moot as to Ni proposed count 2, granted as to the 29 July 1997 filing date of the 601054,021 application for Count 1 and otherwise denied. Ni substantive motion 3 seeking judgment that all Rauch's involved claims are unpatentable under 35 U.S.C.

5 102(e) as anticipated by U.S. Patent 6,872,568

is denied. Ni miscellaneous motion 4 to exclude certain evidence is denied. Rauch substantive motion Ifor benefit for the purpose of priority as to Count 1 is granted as to the 28 March 1997 and 4 June 1997 filing dates of applications 08/829,536 and 08/869,852, respectively, and otherwise denied. Rauch substantive motion 2 to designate Ni claims 46, 55, 63, 64, 110 and 118 as corresponding to Count 1 is denied. Rauch substantive motion 3 is granted to the extent that Ni claims 35, 36, 38-45,47-54, 56-61, 75, 83, 92, 99, 100, 102109, 111-116, 127-133, 168-178 and 180-203 are unpatentable under 35 U.S.C.

5 102(e) as anticipated by U.S. Patent 6,072,047,

moot as to anticipation under

3 102(e) by US. Patents 6,642,358 and 6,569,642, and otherwise denied.
Rauch responsive motion 4 is dismissed as moot in view of the denial of Ni substantive motion 1. Rauch miscellaneous motion 5 to exclude certain evidence is dismissed as moot.

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Interference No. 105,381 Human Genome Sciences, Inc. (Ni) v. lmmunex Corp. (Rauch)

II.

Findings of Fact (FF)

The following findings of fact are supported by a preponderance of the evidence.
1. The junior party is Jian NI, Reiner L. GENTZ, Guo-Liang YU and Craig A.

Rosen ("Ni").
2. Ni is involved in the interference on the basis of application 101005,842

("the '842 application," NX 2025), filed 7 December 2001.
3. The '842 application has been accorded benefit for the purpose of priority

of the 17 March 1998 filing date of application 091042,583 ("the '583 application," NX 2024).
4.

Ni's real party-in-interest is Human Genome Sciences, Inc. ("HGS").

5. The senior party is Charles RAUCH and Henning WALCZAK ("Rauch").
6. Rauch is involved in the interference on the basis of U.S. Patent

6,642,358 ("the '358 patent," RX 1012), issued 4 November 2005, based on application 091578,392 ("the '392 application"), filed 25 May 2000.
7.

The '392 application has been accorded benefit for the purpose of priority
of the 26 June 1997 filing date of application 081883,036 ("the '036 application," RX 1018), which issued 6 June 2000 as U.S. Patent 6,072,047 ("the '047 patent," RX 1048)

8.

Rauch's real party-in-interest is lmmunex Corp. ("lmmunex").

9. The subject matter of the interference is defined by one count.
10.

Count Iis "Claim 6 of U.S. Patent 6,642,358 (Paper I, 3). p.

I Claim 6 of the '358 patent, written in independent form, reads: I.

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Interference No. 105,381 Human Genome Sciences, Inc. (Ni) v. lmmunex Corp. (Rauch) A purified TRAIL-R polypeptide comprising an amino acid sequence that is at least 90% identical to the amino acid sequence presented in SEQ ID NO:2 wherein said polypeptide binds TRAIL.
12. According to

the '358 patent, SEQ ID NO:2 is the 440 amino acid

sequence of a full length human receptor protein (including the Nterminal signal peptide), "TRAIL-R," encoded by the DNA of SEQ ID NO:l (RX 1012, c. Ill.66 - c. 2,l. 2 and c. 22, 11. 7-11).
13. The claims of the

parties are: 35-72,75, 83, 92, 99-133, 152-178 and 180-203 1-41

Ni Rauch

14. The claims of the parties which correspond to Count 1 are: Ni Rauch 35,36,38-45,47-54, 56-61,75, 83, 92, 99, 100, 102109, 111-116, 127-133, 168-178 and 180-203 1,4-6, 8-1 I , 17-19, 26-28, 34, 37,38and 40

I The claims of the parties which do 5.

not correspond to Count 1, and

therefore are not part:of this interference, are:

Ni Rauch

37,46, 55,62-72, 101, 110, 117-126 and 152-167 2, 3,7, 12-16, 20-25,29-33, 35, 36, 39 and 41

Other findings of fact follow below.

Ill.

Ni Substantive Motion I Pursuant to 37 CFR 5 41.21(a)(l)(i), Ni moves to redefine the scope of I

the interference by substituting proposed count 2 for current Count 1 (Paper 29). Rauch opposes (Paper 52); Ni replies (Paper 60).
16. Ni's proposed count 2 reads (Paper 29, p. I, I): 7

A purified TRAIL-R polypeptide comprising an amino acid sequence that is at least 90% identical to the amino acid sequence presented in SEQ ID NO:2

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Interference No. 105,381 Human Genome Sciences, lnc. (Ni) v. lrnmunex Corp. (Rauch)

wherein said polypeptide binds TRAIL or induces apoptosis.
17. According to Ni, its proposed count 2 simply incorporates Rauch claims 5

and 6, as does the current count, and adds the language "or induces apoptosis" (id.). It is our understanding that the source of SEQ ID NO:2 in Ni's proposed count 2 is the involved '358 patent of Rauch. With this understanding, we now address Ni motion 1. Ni argues that the abilities to bind TRAIL and to induce apoptosis are inherent properties of the polypeptide of Count 1, although only the former is expressly recited in the count (Paper 29, p. 7, fi 3). A party seeking to change the count in an interference must demonstrate a genuine need to change the count. As stated in Louis v. Okada, 59 USPQ2d 1073, 1076 (Bd. Pat. App. & Int.

[a]t a minimum, ... a preliminary motion to broaden out the count on the basis that a party's best or earliest proofs are outside the current count (1) should make a proffer of the patty's best proofs, (2) show that such best proofs indeed lie outside of the scope of the current count, and (3) further show that the proposed new count is not excessively broad with respect to what a party needs for its best proofs.

Ni seeks to change the count by adding the limitation "orinduces
apoptosis" as an alternative to the limitation "binds TRAIL" (FF 16). Ni seeks to change the current count because its best proofs do not exglicitlv recite that the TRAIL-R polypeptide of the count binds TRAIL (FF 18). However, the fact that Nils "best proofs" do not explicitly recite the language of the count does not alone

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Interference No. 105,381 Human Genome Sciences, Inc. (Ni) v. lmmunex Corp. (Rauch)

establish that those proofs are not directed to "subject matter" defined by the count. "The invention is not the language of the count but the subject matter thereby defined." Silvestri v. Grant, 496 F.2d 593, 598, 181 USPQ 706, 709
(CCPA 1974). In appropriate circumstances, express limitations of the count

may be shown to be inherent in the proofs, id. ("In reaching this conclusion, we
do not disregard the fact that the count also requires that the ampicillin possesses greater storage-stability than hydrated ampicillin and have a molecular weight of about 349. However, we regard these as inherent properties of Form II ampicillin which add nothing to the count definition beyond that determined by the [other limitations].").' The limitation said not to be disclosed by Nils best proofs, i-e., the ability to bind TRAIL, may be shown to be an inherent property of the TRAIL-R polypeptide of the count. In fact, Ni argues that the ability to bind TRAIL and the ability to induce apoptosis are both inherent properties of the TRAIL-R polypeptide of the count:

The ability to bind TRAIL is an expressly recited
property of the polypeptide and it is an inherent property of the polypeptide of SEQ ID NO:2. Similarly, the ability of the polypeptide of SEQ ID NO:2 to induce apoptosis is also an inherent property of the polypeptide of SEQ ID NO:2. [Paper 29, p. 7,7 3 (citation to material facts omitted).] Additionally, Ni has not asserted that there are polypeptides meeting the amino acid sequence
In Silvestri, the count was directed to a new crystalline form of ampicillin which was "substantially free of water in the chemically bound state" and had a molecular weight of about 349, a particular infrared ("IR) spectrograph and improved storage stability vis-svis the 496 F.2d at 595-96, 181 USPQ at 709-710. The court previously known form of ampicillin. Id., held that it was sufficient to possess the claimed compound and to characterize it by its water content and IR spectrograph, without demonstrating the knowledge of the ampicillin's molecular weight because the molecular weight lladd[s] nothing to the count beyond that determined by the water content and infrared spectrograph." Id.,496 F.2d at 599, 181 USPQ at 709.

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InterferenceNo. 105,381 Human Genome Sciences, Inc. (Ni) V. lmrnunex Corp. (Rauch)

requirements of the count which would induce apoptosis, but not bind TRAIL. Consequently, adding the phrase "or induces apoptosis" to Count 1 has not been shown to be necessary to encompass Nils best proofs. Furthermore, changing the scope of the count would leave Ni in essentially the same position it is in now of having to prove an inherent property of the TRAIL-R polypeptide of the count
(FF d ) Hence, Ni has failed to demonstrate that its best proofs are outside the 8.

scope of the current count and, therefore, that there is a genuine need to change the count. Based on the foregoing, N substantive motion 1 is denied. i

IV.

Rauch Responsive Motion 4
Pursuant to 37 CFR 5 41.121(a)(2), Rauch moves to be accorded benefit

for the purpose of priority of the (i) 26 June 1997, (ii) 4 June 1997, (iii) 28 March 1997, (iv) 12 March 1997 and (v) 13 February 1997 filing dates of U.S. applications (i) 081883,036, (ii) 081869,852, (iii) 081829,536, (iv) 08/815,255 and (v) 081799,861, respectively, as to Ni's proposed count 2 (Paper 45). Rauch responsive motion 4 is contingent upon the grant of Ni substantive motion Ito substitute Ni's proposed count 2 for current Count 1. Since the contingency has not occurred, Rauch responsive motion 4 is dismissed as moot.
V.

Ni Substantive Motion 2

Pursuant to 37 CFR $41.I21(a)(l)(ii), Ni moves to be accorded benefit for the purpose of priority of the 17 March 1997 and 29 July 1997 filing dates of its earlier filed provisional applications 60/040,846 ("the '846 application," NX 2042) and 601054,021 ("the '021 application," NX 2056), respectively, as to Count 1

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and, contingent on the grant of Ni substantive motion 1, as to Ni's proposed count 2 (Paper 30). Rauch opposes (Paper 53); Ni replies (Paper 61). To the extent Ni substantive motion 2 is contingent upon the grant of Ni substantive motion 1, it is dismissed as moot because the contingency has not occurred. As discussed above, the subject matter of Count Iis directed to a purified TRAIL-R polypeptide having an amino acid sequence that is at least 90% identical to SEQ ID NO:2 of Rauch's involved '358 patent, wherein the polypeptide binds TRAIL (FF 11).
18. TRAIL (TNF-Related Apoptosis-Inducing Ligand) is a member of the TNF

ligand family known to be capable of inducing apoptosis when added to certain cells, e-g., Jurkat cells (NX 2096').

is. The '021 and '846 application are both provisional applications.
20. The '021 application was filed 29 July 1997 (NX 2056, cover sheet).
21.

The '846 application was filed 17 March 1997 (NX 2042, cover sheet).

22. Figure 1 of the '021 application is said to show the nucleotide and

deduced amino acid sequences of "human Death Domain Containing Receptor 5" (DR5) obtained from the cDNA clone deposited as ATCC Deposit No. 97920 on 7 March 1997 (NX 2056, p. 1,Il. 7-9; p. 6, 11. 5-6; p. 7,Il. 29-33; p. 9,ll. 9-12; p. 10, 11. 34-35).
23. According to the '021 specification, DR5 is a 41 1 amino acid protein (id.,

p. 26, 11. 9-10).
2

Wley et al., "Identificationand Characterization of a New Member of the TNF Family that Induces Apoptosis," Immunity, Vol. 3, pp. 673-682 (December 1995) (NX 2096).

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24. Example 6 of the '021 specification is said to show that a DR5

extracellular domain-Fc fusion construct (DR5-Fc) binds TRAIL (id., p. 50, 1. 6 - p. 51,l. 2; Figures 6A-6C).
25. Figure 1 of the '846 application is said to show the nucleotide and

deduced amino acid sequences of DR5 obtained from the cDNA clone deposited as ATCC Deposit No. 97920 on 7 March 1997 (NX 2042, p. I,

11. 5-6; p. 3, 11. 22-25; p. 5, 11. 24-27).
26. According to the '846 specification, DR5 is a 41 1 amino acid protein (id.,

p. 6, 11. 25-27).
27. Figure 2 of the '846 application is said to compare the deduced amino

acid sequence of DR5 to the amino acid sequences of three known TNF family death receptor proteins -- human tumor necrosis factor receptor 1 (human TNFRI), human Fas protein and DR3 protein @., p. 5, 11.8-13).
28. According to the '846 specification, similarities between the amino acid

sequences shown in Figure 2 "strongly suggest that DR5 is also a death domain containing receptor with the ability to induce apoptosis," i.e., that DR5 is a putative death receptor protein of the TNF receptor family

a., 11. 31-33, emphasis added). p. 6,

29. Further according to the '846 specification, "TNF-family ligands induce

various cellular responses by binding to TNF-family receptors, including the DR5 of the present invention. Cell which express the DR5 polypeptide are believed to have a potent cellular response to DR5 ligands ... " (id., p. 26, 11. 12-15, emphasis added).

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30. The '846 specification defines "TNF-family ligand" as

naturally occurring, recombinant, and synthetic ligands that are capable of binding to a member of the TNF-receptor family and inducing the ligandlreceptor signaling pathway. Members of the TNF ligand family include, but are not limited to, DR5 ligands, TRAIL, TNF-a, lymphdtoxin-a (LT-a, also known as TNF-a), LT-8 (found in complex heterotrimer LT-a2-B), FasL, CD40, CD27, CD30,4-lBB, OX40 and nerve growth factor (NGF). p. 31, 11.4-9, emphasis added.]

u.,

31. The amino acid sequence of the DR5 protein shown in the respective

Figures 1 of the '021 and '846 applications are identical.
32. It is undisputed that the amino acid sequences shown in Figures 1 of the

'021 and '846 applications are at least about 93% identical to the amino acid sequence of SEQ ID NO:2 as recited in Count 1, with 411 of 440 total amino acids being identical (see Paper 53, p. 22 where Rauch admits Nils Statement of Material Facts (SMFs) 7 and 8 as set forth in Paper 30, p. 26).
33. Thus, the '021 application describes an enabled embodiment within the

scope of Count 1, i.e.,a DR5 polypeptide having an amino acid sequence that is at least 90% identical to the amino acid sequence of
SEQ ID NO:2 of the '358 patent (FFs 22, 31 and 32) and which binds

TRAIL (FF 24).
34.

Rauch does not dispute Ni's claim to benefit for the purpose of priority of the filing date of the '021 application (Paper 53).

Based on the foregoing, we accord Ni benefit for the purpose of priority of the filing date of the '021 application as to Count 1.

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While the '846 application describes (Figure I ) a DR5 polypeptide having a deduced amino acid sequence which is at least 90% identical to the amino acid sequence set forth in SEQ ID NO:2 of the '358 patent (FF 32),the disclosure of the '846 application suaaests that the DR5 polypeptide is a death domain containing receptor with the ability to induce apoptosis (FF 28). However, the disclosure of the '846 application does not describe preparing a DR5 polypeptide (or ligand binding portion thereof) or binding the ligand TRAIL to the DR5 polypeptide (or ligand binding portion thereof). Rather, the disclosure of the '846 application suclaests that a DR5 polypeptide binds a "DR5 ligand" (FFs 29 and

30).
Ni's position is premised on classifying DR5 as a "putative TNF death receptor" based on the described similarity between the amino acid sequences of DR5 and three previously known TNF death receptors TNFRI, Fas and DR3 in the '846 application. According to Ni, TNFRI, Fas and DR3 were all known to induce apoptosis upon activation and, therefore, that same function should be imputed to DR5 by virtue of the described similarity in amino acid sequences between DR5 and the three TNF death receptors. Ni argues that the '846 specification explicitly teaches that DR5 induces apoptosis and binds to a TNF ligand selected from a limited list including TRAIL. Ni further argues that, based on the doctrine of inherency, the '846 application need not expressly recite that DR5 binds TRAIL so long as the '846 application describes the subject matter of the Count. [Paper 30, p. 2,13and 7 bridging pp. 9-10.]

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35. Ni relies on the direct testimony of John C. Reed, M.D., Ph.D. (NX 2103)

in support of its position.
36.

Dr. Reed has been qualified as an expert to give opinions on the subjects of apoptosis and of the tumor necrosis family of ligands (TNFs) and receptors (TNFRs), including death receptors.

37. According to Dr. Reed, the deduced amino acid sequence of human OR5

described in the '846 application has all the canonical (structural) features of a classic death receptor of the TNFR family, i.e., a leader peptide, conserved cysteine-rich domain(s), a transmembrane domain and a cytosolic domain containing a "death domain1'(NX 2103,T 28).
38. Further according to Dr. Reed, the death domain "is necessary and

sufficient for apoptosis induction, at least when overexpressed in mammalian cells" (id.,fl21).
39. Still further according to Dr. Reed, DR5 shares the highest degree of

amino acid sequence identity with then known death receptor proteins human TNFRI, Fas and DR3
40.

(a,,7 29).

Dr. Reed states that the deduced amino acid sequence of the "death domain" region of the DR5 protein described in Ni's '846 application was approximately 21, 32 and 33 percent identical to the amino acid sequences of the death domains of Fas,TNFRI and DR3, respectively, "using Lipman-Pearson Protein Alignment (with the following parameters: Ktuple 2; Gap Penajty 4; Gap Length Penalty 12)" (id., fi 31).

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41, Dr.

Reed opines that a death domain amino acid sequence identity of

approximately 21-33 percent is "significant" because Chinnaniyan (NX 2058) reported that the death domain of DR3 was 47 and 23 percent identical to that of TNFRI and Fas, respectively, while Marsters (NX 2059) reported that the death domain of DR3 was 48 and 20 percent identical to that of TNFRI and Fas, respectively (NX 2103,q 31).
42.

Chinnaiyan reported using ~ e g ~ l i g n " software to align the compared amino acid sequences (NX 2058, Fig. 1).

43.

~ e g ~ l i software can create alignments between two or more gn~~ sequences according to different methods, e.g., the clustal method or the Jotun Hein method (see e.g., U.S. Patent 6,277,568, col. 8, 11. 22-41).

44.

Neither Chinnayian or Marsters reported the alignment program and parameters used to obtain their respective percent sequence identity scores.

45.

Dr. Reed did not explain percent sequence identity scoring, e.g., how different alignment methods and parameters calculate percent sequence identity scores; how different alignment methods are compared (normalized to account for the use of different parameters, e.g., sequence lengths, gaps, gap positions, etc.); the significance, if any, of comparing sequences within predicted structural features (e-g., a death domain or extracellular domain) versus over the entire primary amino acid sequence; standard error of the method(s) used; use of iteration, etc.

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46.

For example, according to ~ a r t a g l i a , ~ [i]t has been noted previously that the intracellular domain of TNF-Rl shares a weak homology (29% identity over 45 amino acids) with the intracellular domain of Fas antigen. Upon further inspection of these sequences, we noted that introduction of a A amino acid gap in the Fas sequence extended the region of homology an additional 20 amino acids (Figure 3). [NX 2067, p. 846, col. 2,7 1, emphasis added.]

47.

Nonetheless, Dr. Reed believes that one of ordinary skill in the art would have reasonably expected the putative death receptor DR5 of the '846 specification to have utilities similar to the known utilities of known death receptors TNFR1, Fas and DR3 (NX 2103, 33-34).

48. According to Dr. Reed, "the most reasonable conclusion to draw from

Nits March 17, 1997 application is that DR5 is expected, by persons of ordinary skill in the art, to be a novel death receptor" and, therefore, skiled artisans "would have predicted that activation of DR5 would induce apoptosis" (NX 2103,n 32, emphasis added).
49. Further according to Dr. Reed, activation (aggregation) of a death

receptor could be caused by (i) ligand binding to the death receptor, (ii) antibody binding to the death receptor or (iii) overexpression of the death

I, . receptor on the cell surface &fi 24).

so. Dr. Reed testified that
if one would want to determine which TNF ligand DR5 binds, Nils March 17, 1997 application [i.e., the '846 application], in combination with what was known in the art at the time, provides all of the necessary I information. For example, Nits March ' 7, 1997
Tartaglia et a!. (Tartaglia), "A Novel Domain within the 55 kd TNF Receptor Signals Cell Death,"

Cell, - Vol. 74, pp. 845-853 (10 September 1993) (NX 2067).

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application states that DR5 binds to a TNF-family ligand (Exhibit 2042, pg. 4, m2-3; pg. 26,nl; pgs 2829; pg. 31,flI, pg. 31, fll [sic]), which would have been expected by a person of ordinary skill in the art in view of the literature that was available by March 17, 1997. Additionally, Nils March 17, 1997 application specifically defines "a TNF family ligand" as a limited number of molecules, one of which is TRAIL. (Exhibit 2042, pg. 31, lines 4-9). The Ni March 17, 1997 application also teaches assays, such as cellular response assays, that could be used t o determine whether TRAIL, or any other of the listed TNF ligands, binds to DR5. (Exhibit 2042, pg. 26, lines 12-26; pg. 27, line 21 through pg. 29, line 6). Alternatively, as of March 17, 1997, it would have been routine for a person of ordinary skill in the art to have tested whether DR5 binds to the TNF-family ligands recited in Ni's May [sic] 17,1997 application, including TRAIL. Thus, if one wanted to have determined whether DR5 bound to a TNF ligand, including TRAIL, the Ni March 17, 1997 application, in combination with what was known in the art at the time, teaches all of the needed information. [NX 2103, n56, emphasis and bracketed text added.]
51. Dr. Reed notes that while most TNF family receptors have been shown

experimentally to bind to specific TNF family ligands, some receptors "do not have known receptors to date, or a delay of many years occurred before the specific ligand was established" (NX 2103, 718).
52. According to the '846 specification, there are eleven known members of

the TNF ligand family, i-e., TNF-a, lymphotoxin-a (LT-a, also known as TNF-a), LT-13 (found in complex heterotrirner LT-a2-a), FasL, CD40, CD27, CD30,4-IBB, 0x040, nerve growth factor (NGF) and TRAIL (NX 2042, p. 1, 11. 21-25 and p. 31,Il. 6-9).
53.

The '846 specification defines "TNF-family ligand" as

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naturally occurring, recombinant, and synthetic ligands that are capable of binding to a member of the TNF receptor family and inducing the ligandlreceptor signaling pathway. Members of the TNF ligand family include, but are not limited to, DR5 ligands, TRAIL, TNF-a, lymphdtoxin-a (LT-a, also known as TNF-a), LT-I3 (found in complex heterotrimer LT-a2-a), FasL, CD40, CD 27, CD30,4-1 BB, OX40 and nerve growth factor (NGF). p. 31, 1. 4-9, emphasis added.] 1

w.,

54.

Dr. Reed relies on Nils later filed '201 application (NX 2056, Figure 6A) and on a later published August 1997 article (NX 20314) to support his testimony that DR5 "necessarily" binds to TRAIL and "necessarily" induces apoptosis (NX 2103, 7 57).

To be accorded benefit for the purpose of priority in an interference proceeding "means Board recognition that a patent application provides a proper constructive reduction to practice under 35 U.S.C. 102(g)(l)." 37 CFR 5 41.201.

A constructive reduction to practice "means a described and enabled anticipation
under 35 U.S.C. 102(g)(l) in a patent application of the subject matter of a count."

Id. To fulfill the written description requirement, the patent specification

must describe an invention in sufficient detail that one skilled in the art can clearly conclude that the inventor invented what is claimed. Lockwood v. Am. Airlines, Inc., 107 F.3d 1565, 1572,41 USPQ2d 1961, 1966 (Fed. Cir. 1997). The specification "need not describe the claimed subject matter in exactly the same terms as used in the claims; it must simply indicate to persons skilled in the art that as of the [filing] date the applicant had invented what is now claimed." Eiselstein v. Frank, 52 F.3d 1035, 1038, 34 USPQ2d 1467, 1470 (Fed. Cir. 1995)
Guohua et al. (Guohua), "An Antagonist Dewy Receptor and a Death Domain-Containing Receptor for TRAIL," Science, Val. 277, pp. 815-818 (8 August 1997). Three of the six coauthors are also Ni inventors.

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(citations omitted). Furthermore, "the fact that a characteristic is a necessary feature or result of a prior-art embodiment (that is itself sufficiently described and enabled) is enough for inherent anticipation, even if that fact was unknown at the time of the prior invention." Toro Co. v. Deere & Co., 69 USPQ2d 1584, 1590 (Fed. Cir. 2004) (citations omitted). Benefit for the purpose of priority focuses on the subject matter of a count and only requires a constructive reduction to practice of a single embodiment within the scope of the count. FaIkner v. Inqlis, 463 F.3d 1376, 1379,79 USPQ2d 1001,1004 (Fed. Cir. 2006); Hunt v. Tre~~schuh, F.2d 1386,1389,187 USPQ 426,429 (CCPA 1975).' 523 Here, the subject matter of the count is directed to a functional protein, i.e., a purified TRAIL-R polypeptide having an amino acid sequence that is at least 90% identical to SEQ ID NO:2 of Rauch's involved '358 patent, wherein the polypeptide binds TRAIL (FF 11). Relying on the testimony of Dr. Reed, Ni argues that the similarity between the deduced amino acid sequence of DR5 and the known amino acid sequences of three TNF death receptor proteins, i.e., TNFRI, Fas and DR3, as described in the '846 application is sufficient to characterize DR5 as a putative TNF death receptor protein and to predict that
Dl35 has utilities/functions similar to those of known death receptor proteins, e.g.,

induction of apoptosis upon activation. Neither the disclosure of the '846 application nor the testimony of Dr. Reed is as explicit as Ni argues. The '846 application suagests that DR5 is a putative
TNF death receptor protein (FF 28). Dr. Reed testified that the most reasonable
In contrast, benefit for the purpose of 35 U.S.C. § 120 and related statutes focuses on the subject matter of the claim and requires the application for which benefit is sought to describe and enable the entire scope of the claim.

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conclusion a person of ordinary skill in the art would draw from the '846 application is that DR5 "is expected ... to be a novel death receptor" (FF 48).

The '846 specification does not describe preparing DR5 or a ligand binding
portion thereof (e.g., expressing and purifying DR5 from the DNA of Figure 1). The '846 specification does not describe an activated (functional) DR5 or identify the TNF ligand which activates (binds to) DR5. Since TRAIL was known to be capable of inducing apoptosis (FF 18), identifying TRAIL as the TNF ligand which bound to DR5 in the '846 specification would have been one way of describing DR5 as capable of inducing apoptosis. Dr. Reed testified that '846 application "states that DR5 binds to a TNF-family ligand" and that there were "assays, that could be used to determine whether TRAIL, or any other of the listed TNF ligands, binds to DR5" (FF 50). Dr. Reed further testified that "it would have been routine for one of ordinary skill in the art to have tested whether DR5 binds to the TNF-family ligands recited" in the '846 application, "including TRAIL" (FF 50). Notably, the '846 specification enumerates "DR5 ligands" as separate and distinct ligands in its list of TNF ligands, including TRAIL (FF 53), implying that OR5 might bind to either a known TNF ligand, e.g., TRAIL, or an as yet unknown TNF ligand, i.e., a DR5 ligand, or another TNF ligand known to be capable of inducing another function, e.g., cell proliferation. In short, there is neither explicit nor implicit disclosure in the '846 application said to show that the DR5 polypeptide encoded by the DNA of Figure

Iis a functional/bioactive protein. The cognate ligand for DR5 is not explicitly

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identified in the '846 application, although it would have been routine for one of ordinary skill in the art to do so using known techniques, as testified to by Dr. Reed (FF 50). Moreover, there could be no explicit description of an activated DR5 based on antibody binding or overexpression in mammalian cells absent obtaining the DR5 polypeptide (e.g., by expressing the product of the DNA of Figure 1) against which to raise an antibody. Finally, a person skilled in the art could not have reasonably predicted the function&) of DR5 based solely on the similarity between its deduced amino acid sequence as set forth in Figure 1 of the '846 application and the known amino acid sequences of TNFRI, Fas and

DR3 in view of the state of the art when the '846 application was filed for the
following reasons. Genes encode proteins by providing a sequence of nucleic acids that is translated into a sequence of amino acids. Methods used to identify novel genes are classified into two types, i.e., homology based or non-homology based. In homology based methods, for example, clones from a cDNA library are cloned and analyzed (sequenced). The resultant nucleotide sequences andlor deduced amino acid sequences are checked against databases for similarity (homology) to previously characterized sequences on the theory that molecules with simiIar sequences would be expected to perform similar functions. However, one of the difficulties in identifying a functional protein is that function depends not only on the amino acid sequence of the protein, but also on other factors, e.g., the threedimensional structure of the protein.

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In order for a protein to function properly its amino acid sequence (primary structure) must fold itself up into a complex three-dimensional shape which allows for molecular recognition. Molecular recognition often involves only a small number of key amino acid residues on the functional surfaces of interacting molecules. These residues are dispersed in diverse regions of the primary amino acid sequence due to the complex structural organization of the protein. There are multiple levels to the structural organization of a protein. The primary

structure of a protein refers to the linear arrangement of amino acid residues
along a polypeptide chain. Secondary structures form through interactions between amino acids typically found near each other in the peptide chain which fold parts of the chain into regular structures, e.g., a helices and I3 sheets.
Tiediary structure folds both the secondary structures and the regions between

them into compact three-dimensional shapes in an energetically favourable way.

Quaternary structure refers to the organization of several polypeptide chains into
a single protein molecule, e.g., hemoglobin is a tetramer. Consequently, amino acid residues rather near to each other in a protein's primary structure may be rather distant in the protein's ultimate quaternary structure. [See generally, MOLECULAR CELL BIOLOGY ("MCB), second edition, Darnell et al., W.H. Freeman and Company, New York, NY ( I 990), pp. 44-48 (copy enclosed).] For example, an enzyme is a protein that catalyzes a biochemical reaction. The function of an enzyme relies on the structure of its "active site," a specific cavity-like region on the surface of the three-dimensional enzyme which allows a spatial f (molecular recognition) between the enzyme and its substrate t i

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(reactant in the reaction being catalyzed). The active site contains key amino acids that bind the substrate and are involved in the reaction catalyzed by the enzyme. These key amino acids are brought into proximity (into the active site) by protein folding. [See generally, MICROBIOLOGY: An Introduction, Tortora et al., The BenjaminICummings Publishing Company, Inc., Menlo Park, California
1 ( I982), pp. I 1-112, copy enclosed; MCB, pp. 55-65, copy enclosed.]

On the other hand, mutations that cause human disease often disrupt protein structure, thereby altering or abolishing normal protein function. For example, sickle cell anemia occurs in humans that are homozygous for a l3hemoglobin gene that differs from the normal adult hemoglobin gene by a single base pair, resulting in a change in a single amino acid @omglutamate to valine in position 5. This substitution is on the surface of the abnormal hemoglobin (Hb S) and changes the electrostatic charge on the surface of Hb S.

When oxygen is

removed from Hb S, the protein polymerizes into rigid crystals that deform a sickle cell patient's red blood cells. Thus, although normal hemoglobin and Hb S have virtually identical primary amino acid sequences, a single amino acid change in Hb S alters its quaternary structure and results in abnormal protein function. [See generally, CLINICAL DIAGNOSIS AND MANAGEMENT BY LABORATORY METHODS, sixteenth edition, J.B. Henry ed., W.B. Saunders Company, Philadelphia (1979), Vol. I,p. 992, copy enclosed.] Therefore, "[~Jequence comparison can indicate whether an RNA or protein molecule or region of DNA is already known (identity) or has some degree of similarity to a known sequence" (MOLECULAR BIOLOGY AND

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BIOTECHNOLOGY, R. Myers, ed., VCH Publishers, Inc., New York, NY (1995), p. 860, c. I, I, 7 copy enclosed). However, since "[tlhe function of nucleic acids and proteins depend on their structure and involves complex interactions in three dimensions", [ijt is not presently understood whether it is possible, in general, to derive structure from sequence. Sequence alone is therefore often inadequate to determine function. Predictions made from sequence analysis need to be experimentally tested. Nonetheless, computer analysis of sequences is valuable in suggesting the most useful experiments to perform. [Id.,p. 860, c. 1 , y 2.1 Indeed, the difficulties in predicting the structure and function of a protein from just its amino acid sequence (primary structure) are so well known in the art that the ability to characterize the function and structure of a protein from its amino acid sequence has been called the "Holy Grail" of molecular biology (RX 1061,6 p. 511, c. 2,11top. 512, c. 1 , y l ) .
55. Genchong Cheng, Ph.D., is a witness for Rauch and has been qualified

as an expert to give opinions on the subjects of signal transduction and gene expression networks through the TNFR, Toll-like receptor (TLR) and Nod receptor families during immune responses.
56. Dr. Cheng testified that

[slequence homology to other death domaincontaining TNF receptors may be sufficient to convince one of ordinary skill in the art that a novel protein is a TNFR family member. However, sequence homology alone is not sufficient to support an assertion that a novel TNFR family member protein will induce specific biological activities such as
Pawlowski et al., "from fold to function predictions: an apoptosis regulator protein BID," Computers and Chemistry, Vol. 24, pp. 511-517 (2000) (RX 1061).

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apoptosis. Wlthout additional data regarding the activity of a TNFR family member, such as, for example, the identity of the ligand with a known function (such as TRAIL) to which the receptor binds, one of ordinary skill in the art cannot reasonably predict the function of the TNFR family member. [RX 1039,y 17.1 Ni's own witness, Dr. Reed, did not testify that the specification and figures of the '846 application would have reasonably conveyed to a skilled artisan that a
DR5 having the deduced amino acid sequence shown in Figure 1 is in fact a

functional death receptor protein based solely on its amino acid sequence (primary structure). Dr. Reed did not testify that the skilled artisan would have understood the '846 application to describe a functional death receptor. Rather, Dr. Reed testified to ''the most reasonable" (not the necessary and always) conclusion that one of ordinary skill in the art would have drawn from the disclosure of the '846 application (FF 48).

Dr. Reed also testified that there was a "significant" percent sequence
identity between the deduced amino acid sequence of DRS's death domain and the amino acid sequence of the death domains of TNFRI, Fas and DR3 (FFs 40 and 41). However, Dr. Reed's testimony in this regard is entitled to little, if any, weight because Dr. Reed did not provide a sufficient basis for his opinion. Dr. Reed did not explain how percent sequence identity scores were obtained, identify what alignment methods and parameters were used by the "references" (Chinnaiyan (NX 2058)~ Marsters (NX 2059j8), explain how percent identify and

7

Chinnaiyan et al. (Chinnaiyan),"Signal Transduction by DR3, a Death Domain-Containing Receptor Relatedto TNFR-1 and CD95,"Science, Vol. 274, pp. 990-992 (8 November 1996) (NX 2058).
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scores based on different alignment methods and parameters relate to each other, what standard of error was typically found, whether iteration was necessary to obtain a statistically valid result, etc. 37 CFR 5 41.158; Standing Order 7 24. Further, as illustrated by the discussion of Hb S above, even very small differences between protein variants with highly similar amino acid sequences can produce significant differences in function. Therefore, in view of the state of the art at the time the '846 application was filed and the testimony of both Drs. Reed and Cheng, we find that the '846 application does not describe an enabled embodiment (a functional DR5 having the deduced amino acid sequence shown in Figure 1) within the scope of Count

I. The '846 application does describe a OR5 which may be preliminarily
classified as a TNF death receptor protein based upon its deduced amino acid sequence. However, given the unpredictability of determining function from structure, a skilled artisan would have had to carry out further research to identify the function(s) of DR5 having the deduced amino acid sequence set forth in Figure 1. Anticipation is a question of fact, not a conclusion of law, no matter how reasonable that conclusion may appear to be. Putative assignment to a protein (sub)family does not assess the actual biological functionlutility of a nucleic acid sequence and its encoded protein product. Ni has failed to establish that the
'846 application describes a functional death receptor protein within the scope of

the count based solely on the disclosure of a deduced amino acid sequence.
Marsters et al. (Marsters), "Apo-3, a new member of the tumor necrosis factor receptor family, contains a death domain and activates apoptosis and NF-KB,"Current Bioloay,Vol. 6, No. 12, pp. 1669-1676 (1996) (NX 2059).

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Brenner v. Manson, 383 U.S. 519,532,148 USPQ 689,694 (1966) ("the presumption that adjacent homologues have the same utility has been challenged in the steroid field because of 'greater known unpredictability of compounds in that field."'). Ni also argues that the DR5 protein of the '846 application inherently binds TRAIL and that the '846 specification explicitly teaches that DR5 binds a TNF ligand selected from a limited list which includes TRAlL (Paper 30, p. 2,7 3). However, before considering whether a limitation is an inherent characteristic of an embodiment within the scope of a count, that embodiment must itself be sufficiently described and enabled.

m,69 USPQ2d at 1590. Thus, this

argument fails because Ni has not established that the '846 application describes an enabled embodiment within the scope of the count for the reasons above. Secondly, arguing that DR5 binds a TNF ligand from a limited list which includes TRAIL is also unpersuasive because the so-called "limited" list appears to cover all the known and unknown ligands of the TNF family, i.e., the list enumerates the eleven then known TNF ligands and then adds a catch-all "DR5 ligands," seemingly in the event DR5 did not bind any of the then known TNF ligands. Neither the disclosure of the '846 application nor the testimony of Dr. Reed suggests that DR5 necessarily and always binds TRAIL or that DR5 binds a specific ligand from the "limited" subset of TNF ligands. Moreover, Ni's reliance on case law is misplaced.
Ni argues that

even without express appreciation of a limitation recited in a count, disclosure in a priority application of an embodiment which is later shown to inherently Letter Brief Ex. C D-M

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possess a characteristic satisfying that limitation is sufficient to establish constructive reduction to practice. See e.g., Silvestri v. Grant, 496 F.2d 593, 599, 181 U.S.P.Q. 706, 710 (CCPA 1974) ("The s invention i not the language of the count but the subject matter defined thereby."); See also Hudziak v. Ring, 2005 Pat. App. LEXlS 26 (Bd. Pat. App. Inff., Sept. 2005) (confirming that a party's priority applications, which disclosed an antibody but did not state the antibody bound to a particular receptor protein (HER2) as recited in the count, were nonetheless constructive reductions to practice because subsequent evidence showed that the antibody bound HER2.) [Paper 30, p. 8, 1, original emphasis.] Neither Silvestri nor Hudziak are on point. Silvestri has been discussed above (§Ill. Ni Substantive Motion I). In Silvestri, the court held that the evidence established that Silvestri had prepared a new form of ampicillin, recognized and appreciated the existence of the new form of ampicillin, and that the new form of ampicillin had utility.

Id.,496 F.2d at 598-601, 181 USPQ at

709-712. The court acknowledged that the ampicillin of the count required a molecular weight of about 349 and greater storage stability than the previously known form of ampicillin. However, the court thought these were inherent properties of the new form of ampicillin that Silvestri was said to have obtained, recognized and described. Id.,496 F.2d at 599,181 USPQ at 709. The court noted in Silvestri that the reduction to practice test does not require in haec verba appreciation of each of the limitations of the count: This standard does not require that Silvestri establish that he recognized the invention in the same terms as those recited in the count. The invention is not the language of the count but the subject matter thereby defined. Silvestri must establish that he recognized and appreciated as a new form, a compound
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,'I

corresponding to the compound defined by the count. Id 496 F.2d at 599, 181 USPQ at 710

Here, the compound of the count is a functional protein which has at least 90% identity to a defined amino acid sequence and binds TRAIL. Thus, it is necessary to consider whether the '846 application describes propertiesluses of DR5. The '846 application only speculates that DR5 has desired properties, e.g., inducing apoptosis upon activation. Ni is not in the same position as Silvestri whose application was said to have described obtaining an ampicillin compound, to have recognized it as a new form of ampicillin and to have described certain properties of the compound. Nils '846 application describes a precursor to an encoded protein and speculates on the nature and properties of that protein. Therefore, Silvestri is not on point. Similarly, in Hudziak v. Rinq, 80 USPQ2d 1018, 1019 (Bd. Pat. App. & Int. 20