Ex Parte Wikström et al

Board of Patent Appeals and Interferences

Sep 13, 2010

11790465 (B.P.A.I. Sep. 13, 2010)

UNITED STATES PATENT AND TRADEMARK OFFICE
UNITED STATES DEPARTMENT OF COMMERCE
United States Patent and Trademark Office
Address: COMMISSIONER FOR PATENTS
P.O. Box 1450
Alexandria, Virginia 22313-1450
www.uspto.gov
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO.
11/790,465 04/25/2007 Hâkan Vilheim Wikström 072790-0013 1157
20277 7590 09/13/2010
MCDERMOTT WILL & EMERY LLP
600 13TH STREET, N.W.
WASHINGTON, DC 20005-3096
EXAMINER
DESAI, RITA J
ART UNIT PAPER NUMBER
1625
MAIL DATE DELIVERY MODE
09/13/2010 PAPER
Please find below and/or attached an Office communication concerning this application or proceeding.
The time period for reply, if any, is set in the attached communication.
PTOL-90A (Rev. 04/07)

UNITED STATES PATENT AND TRADEMARK OFFICE
____________________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
____________________

Ex parte HÂKAN VILHEIM WIKSTRÖM, DURK DIJKSTRA,
and BASTIAAN JOHAN VENHUIS
____________________

Appeal 2009-014379
Application 11/790,465
to reissue U.S. Patent 6,998,405
Technology Center 1600
____________________

Before JAMES T. MOORE, Vice-Chief Administrative Patent Judge,
MICHAEL P. TIERNEY, and STEPHEN WALSH, Administrative Patent
Judges.

WALSH, Administrative Patent Judge.

DECISION ON APPEAL1

1 The two-month time period for filing an appeal or commencing a civil
action, as recited in 37 C.F.R. § 1.304, or for filing a request for rehearing,
as recited in 37 C.F.R. § 41.52, begins to run from the “MAIL DATE”
(paper delivery mode) or the “NOTIFICATION DATE” (electronic delivery
mode) shown on the PTOL-90A cover letter attached to this decision.
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This is an appeal under 35 U.S.C. § 134(a) involving reissue
application claims to compounds, pharmaceutical compositions, and
methods of treatment. We have jurisdiction under 35 U.S.C. § 6(b).
STATEMENT OF THE CASE
H. Lundbeck A/S, the real party in interest, seeks review of a Final
Rejection mailed May 8, 2008. Claims 1-32, all the pending claims, are on
appeal. A copy of the claims is included in the Claims Appendix of
Appellants’ Brief. (See App. Br. 21-47.)
Claims 1-32 were rejected under 35 U.S.C. § 251 on the ground that
the reissue application improperly attempts to recapture “subject matter not
previously elected.” (Ans. 3.)
Claims 1, 3-4, 10, 19, 25-27 and 31-32 were rejected under 35 U.S.C.
§ 112, first paragraph, based on lack of enablement for the scope claimed.
(Ans. 5.)
We reverse the recapture rejection and affirm the enablement
rejection.
RECAPTURE
The Issue
The historical facts are not in dispute. (See Lundbeck’s Statement
filed April 25, 2007; Ans. 3-5.) During prosecution of the application from
which U.S. Patent 6,998,405 issued, the Applicants were required to divide
the subject matter of the original claims. The Applicants elected the subject
matter related to compounds of “formula If.” The Examiner informed
Applicants that claims directed to the elected subject matter, “formula If,”
were allowable. The Applicants cancelled the original claims and added
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claims 19-21, which issued as claims 1-3, directed to compounds of
“formula If.” The Applicants did not file a divisional application.
Lundbeck filed for reissue of claim 1, amended claims 2 and 3 to
depend on a subsequent new claim, and added new claims 4-32. Lundbeck
characterizes new claims as “linking claims.” The Examiner’s position is:
[a] reissue applicant’s failure to timely file a divisional
application covering the non-elected invention(s) following a
restriction requirement is not considered to be error causing a
patent granted on elected claims to be partially inoperative by
reason of claiming less than the applicant had a right to claim.
Thus, such applicant’s error is not correctable by reissue of the
original patent under 35 U.S.C. 251. See [MANUAL OF
PATENTING EXAMINING PROCEDURE] MPEP § 1412.01.

(Final Rej. 5.)
Lundbeck contends that the Examiner erred because the “basis for the
present reissue application is on the ground that the claims that issued in [the
‘405 patent] were narrower than the disclosure of the patent,” not failure to
file a divisional application. (App. Br. 14.) Lundbeck states that “the new
claims sought to be added through reissue are not the same as the claims that
were non-elected and cancelled from the original application,” and “new
claims 4-32 include compounds and compositions having specific
enantiomeric forms . . . which were disclosed in the specification but not
specifically claimed in the original application.” (Id. at 15.) “[T]he new
claims read on certain subject matter included in the issued claims of the
patent as well as on certain subject matter that was not elected in the original
application. In other words, the new claims are broad enough to read on, or
link, the elected inventions together with the non-elected inventions.” (Id.)
According to Lundbeck, “[s]uch claims have been judicially approved as
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proper for reissue. In re Doyle, 293 F.3d 1355 [] (Fed. Cir. 2002) (holding
that linking claims can be proper subject matter for reissue).” (Id.)
The Examiner responds that “[i]f appellants had filed a divisional then
this reissue request and arguments directed to the linking claims would have
been proper” (Ans. 10), but “[c]laims withdrawn in response to a restriction
requirement for a division ( restriction) cannot be recaptured by a reissue
because the withdrawn [sic] is deliberate” (id. at 18). The Examiner did not
acknowledge Lundbeck’s reliance on the Doyle case.
The issue to be decided is whether the Examiner established that
failure to present linking claims during patent prosecution was an error not
correctable by reissue.
Findings of Fact
1. Within two years of the date Lundbeck U.S. Patent 6,998,405 issued,
Feb. 14, 2006, Lundbeck filed application 11/790,465 on April 25, 2007,
seeking to reissue the patent.
2. As filed, the reissue application contained claims 1-32.
3. Claim 1 is the same as Claim 1 of the patent.
4. Claims 2-32 are new.
5. Claim 4 is a generic claim covering 10 groups of compounds.
6. Included within the 10 groups are the compounds of formula If, the
compounds claimed in Claim 1 of the patent sought to be reissued.
7. At the time the reissue application was filed, Lundbeck also filed a
paper styled “Statement of Status and Support for all Changes to Claims in
U.S. patent No. 6,998,405.”
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8. According to Lundbeck, the patent is “partially defective because the
claims [of the patent] are narrower than the disclosure of the ‘405 patent.”
(Statement 1.)
9. In particular, notes Lundbeck, the patent does not claim specific
enantiomeric forms of the disclosed compounds. (Id.)
10. Lundbeck acknowledges that it did not file a “divisional” before the
‘405 patent issued. (Id. at 2.)
11. Lundbeck characterizes claim 4 as a “linking claim” which differs
from Claim 1 of application 10/737,782 which matured into the patent
sought to be reissued. Lundbeck maintains that presentation of the new
claims, including “linking claim” 4, is authorized by In re Doyle, 293 F.3d
1355 (Fed. Cir. 2002), notwithstanding the fact that Lundberg did not file a
divisional. (Id.)
Principles of Law
“[F]ailure to timely file a divisional application covering the
originally non-elected subject matter [] is not germane to any error in the
prosecution of application I or in the patent resulting therefrom” and is not
an error correctable under 35 U.S.C. § 251. In re Orita, 550 F.2d 1277,
1280 (CCPA 1977). However, the “[Orita] rationale cannot apply” when an
“error in the existing patent [is the] failure to claim as broadly as possible
matter that could have been sought in the original application.” In re Doyle,
293 F.3d 1355 (Fed. Cir. 2002).
Analysis
The claims have not been argued separately, and we select linking
claim 4 as the broadest claim for deciding this issue. 37 C.F.R.
§ 41.37(c)(1)(vii).
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The Examiner’s Answer cited MPEP § 1412.01 for the proposition
that, if an Applicant fails to file a divisional application, the non-elected
inventions cannot be recovered by filing a reissue application. MPEP
§ 1412.01 in turn cites In re Watkinson, 900 F.2d 230 (Fed. Cir. 1990), In re
Mead, 581 F.2d 251 (CCPA 1978), and In re Orita, 550 F.2d 1277 (CCPA
1977), as authority for that proposition. However, § 1412.01 also explains
that failure to file a linking claim may be correctable by reissue. MPEP
§ 1412.01, citing In re Doyle,2 the same case Lundbeck relied on in its
Statement. (FF 11.)
The Doyle decision distinguishes between the circumstance where
subject matter sought on reissue could not have been prosecuted originally,
e.g., because of a restriction requirement, and the circumstance where
subject matter, e.g., a linking claim, could have been sought in the original
application. Doyle, 293 F.3d at 1361. Doyle explains that a linking claim is
distinguishable from claims precluded by the Orita doctrine if the linking
claim could have been prosecuted in the application from which it was
restricted. “The so-called Orita doctrine [] precludes a reissue applicant
from obtaining substantially identical claims to those of nonelected groups
identified in an examiner’s restriction requirement when such claims could
not have been prosecuted in the application from which they were
restricted.” Id. at 1359 (emphasis added). The Doyle court thus
distinguished the Orita doctrine on the ground that Doyle’s “linking claims

2 It appears that the Doyle holding was added to § 1412.01 of MPEP, 8th ed.,
in May, 2004. Compare Revision 1, issued February, 2003, accessible at
www.uspto.gov/web/offices/pac/mpep/old/mpep_E8R1.htm, with Revision
2, issued May, 2004, accessible at
www.uspto.gov/web/offfices/pac/mpep/old/mpep_E8R2.htm.
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not only could have but should have been prosecuted with the elected
group.” (Id. at 1360, emphasis in original.)
The Examiner here adhered to the Orita doctrine; the Examiner did
not acknowledge the Doyle ruling; and the Examiner did not apply a
“Doyle” analysis to Lundbeck’s claims. (See Ans. 18.) In sum, although
Doyle held that linking claims may be sought via reissue if they could have
been prosecuted in the patent application, the Examiner has not explained
why Lundbeck’s claim 4 could not have been prosecuted in the patent
application. Because the rejection did not explain why Doyle does not
control the issue in this case, we reverse.
THE ENABLEMENT REJECTION
The Issues
The Examiner concluded that the Specification does not enable
making and using the invention commensurate in scope with the claims.
(Ans. 5.) In particular, the Examiner identified (1) the scope of R2
substituents, and (2) the variety of diseases to be treated, as beyond the
enabled scope. (Id.) The Examiner performed a Wands factor analysis. (Id.
at 5-9.)
Appellant contends that the full scope of the claims is enabled, and
that the Examiner has not rebutted the evidence provided in the Bang-
Anderson Declaration under Rule 132. (App. Br. 17.)
The issue is whether the totality of the record evidence supports the
Examiner’s conclusion that undue experimentation would have been
required to make and use compositions commensurate with the claim scope.
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Findings of Fact
12. References to the Specification are to the Specification of U.S. Patent
6,998,405, the patent sought to be reissued.
13. Additional findings appear in the Analysis portion of the opinion.
The claims
14. Claim 4 is the broadest claim on appeal.
15. Claim 4 is directed to a Markush group of generic formulas Ia, Ib, Ie,
Ic, If, Id, Ig, Ih, Ii, and Ik, defining numerous compounds.
16. The formulas have R1 and R2 groups and “m” and “n” variables.
Background
17. According to Lundbeck, neurodegenerative diseases are becoming
more prevalent with the aging population. One particular neurodegenerative
disease which typically has its onset between the ages of 50 and 80 years of
age is Parkinson's disease. Parkinson's disease is a disorder of the brain
which is characterized by tremor and difficulty with walking, movement,
and coordination. (Spec., col. 1:19-25.)
18. “Parkinson's disease appears to be caused by a progressive
deterioration of dopamine-containing neurons in the substantia nigra zona
compacta of the brain.” (Id. at col. 1:26-28, emphasis added.) From
Lundbeck's statement, we gather that those skilled in the art are not entirely
sure what causes Parkinson's disease.
19. Dopamine is a chemical neurotransmitter which is utilized by brain
cells to transmit impulses to control or modulate peripheral muscle
movement. The loss of the dopamine-containing neurons results in reduced
amounts of dopamine available to the body. Insufficient dopamine is
thought to disturb the balance between dopamine and other
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neurotransmitters such as acetylcholine. When such dopamine levels are
reduced, nerve cells cannot properly transmit impulses, resulting in a loss of
muscle control and function. (Id. at col. 1:28-38.)
20. Currently [the date of Lundbeck's Swedish application is April 18,
2000], there is no known cure for Parkinson's disease. Typically, treatments
are said to be aimed at controlling the symptoms of Parkinson's disease,
primarily by replacing the dopamine, with either L-DOPA which is
metabolized in the body to dopamine, or by administering chemical agents
that stimulate dopamine receptors. Current treatments are said to slow the
progression of the disease include compounds such as (1) deprenyl
(Selegeline), a selective monoamine oxidase inhibitor, and (2) amantadine,
a compound that appears to decrease dopamine uptake into presynaptic
neurons. (Id. at col. 1, ll. 39-48.)
21. Certain hydroxylated (mono-phenolic or catechols)
phenylethylamines (as such or forming part of a semi-rigid/rigid ring
system) are known to have useful dopaminergic activity. However, their
clinical use is limited because they have low or no bioavailability (high first-
pass effect). (Id. at col. 1, ll. 49-53.)
22. Lundbeck tells us that in 1994 it was reported that (±)-5-keto-2-N,N-
di-n-propylamino-tetrahydrotetralin, a/k/a, (±)-5-keto-DPATT
(id., Formula A, col. 2, l.5) possessed dopaminergic effects in rats in vivo.
However, in vitro binding of this compound does not take place, i.e. (±)-5-
keto-DPATT has itself no affinity to DA receptors. Consequently, it must
be bioactivated before displaying its effects. (Id. at col. 1, ll. 54-62.)
23. Drugs acting as agonists or antagonists on central DA transmission are
said to be clinically effective in treating a variety of central nervous system
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disorders such as parkinsonism, schizophrenia, Huntington's disease and
other cognitive dysfunctions. (Id. at col. 2, ll. 39-43.)
The Lundbeck invention
24. An object of the Lundbeck invention is to provide new prodrugs
which are uniquely metabolized in vivo to a catecholamine derivative that is
a potent dopamine receptor ligand with agonist, partial agonist, inverse
agonist and/or antagonist effects. (Id. at col. 3, ll. 32-36.)
25. A “prodrug” is a class of drugs, the pharmacologic action of which
results from conversion by metabolic processes with the body. STEDMAN'S
MEDICAL DICTIONARY, page 1433 (26th ed. 1995) (ISBN 0-683-07922-0).
A prodrug as administered is inactive; once administered, the prodrug is
metabolized in vivo into an active metabolite (compound). (Id.)
Examiner's § 112 enablement rejection
26. The Examiner rejected claims 1, 3-4, 10, 19, 25-7 and 30-32 under
35 U.S.C. § 112 based on lack of enablement. (Ans. 5.)
27. The Examiner was concerned that the enabling disclosure is not
commensurate in scope with the breadth of the claims. (Id.)
28. In particular, the Examiner stated:
the specification, while being enabling for
1) R2 to be propyl and m to be 2, does not reasonably provide
enablement for all the various R2 substituents such as group
consisting of a hydrogen atom, alkyl or haloalkyl groups of 1 to
7 carbon atoms, cycloalkyl (alkyl) groups of 3 to 7 carbon
atoms, alkenyl or alkyinyl groups of 3 to 6 carbon atoms,
arylalkyl, heteroaryalkyl having 1 to 3 carbon atoms in the alkyl
moiety, in which the aryl/heteroaryl may be substituted; [and]
2) while being enabled for example for formula 6 (formula Ie)
(non-elected) to have some dopamine activity does not have
any enablement for it to treat all the various diseases such as
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Parkinson[s], psychoses, Huntington’s, impotence, [5] renal
failure, [6] heart failure or [7] hypertension.

(Id.)
29. The Examiner then undertook a Wands analysis. (Id. at 5-9.)
30. Lundbeck and the Examiner discussed the Specification and these
additional documents:
Gilbert S. Banker et al., eds, MODERN PHARMACEUTICS, pp. 451, 896 (1996);
F. Zaragosa Dörwald, SIDE REACTIONS IN ORGANIC SYNTHESIS, p. ix (Wiley-
VCH 2005);
Manfred E. Wolff, ed., BURGER’S MEDICINAL CHEMISTRY AND DRUG
DISCOVERY, 5th ed., vol. 1, 975-997 (John Wiley & Sons, rec’d at the
USPTO Feb. 8, 1995);
Benny Bang-Andersen, Declaration under 37 C.F.R. § 1.132 (April 17,
2008);
Ao Zhang et al., Recent Progress in Development of Dopamine Receptor
Subtype-Selective Agents: Potential Therapeutics for Neurological and
Psychiatric Disorders, 107 CHEM. REV. 274-302 (2007) [Bang-Anderson
Decl. Exh. 1];
Ao Zhang et al., Advances in Development of Dopaminergic Aporphinoids,
50 J. MED. CHEM. 171- (2007) [Bang-Anderson Decl. Exh. 2].

31. Declarant Dr. Bang-Anderson states that “[i]n my opinion, a person
skilled in the art pertains can make and use the claimed subject matter . . .
based on the disclosure in the specification coupled with information known
in the art at the time of the application without undue experimentation.”
(Decl. ¶6.)
32. Declarant points to Specification Examples 1-11 and states that “[t]he
specification provides adequate guidance as to how to make compounds
with the various R2 substituents disclosed in the specification.” (Id. at ¶7.)
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33. Declarant states that “[t]he specification further provides guidance as
to how to test the pharmacological effects of the prepared compounds.” (Id.
at ¶8.)
34. Declarant states that “[t]he specification teaches that enantioners can
be prepared by resolving racemic mixtures . . . by chemical or physical
measures that are known to persons skilled in the art.” (Id. at ¶11.)
35. Declarant states that “[c]ompounds having dopaminergic activity with
respect to central dopamine transmission, will show some effect in treating
diseases such as Parkinson, psychoses, Huntington’s, impotence, renal
failure, heart failure or hypertension.” (Id. at ¶12.)
36. Declarant states that “I would expect the compounds with all the
various R2 substituents disclosed and claimed in the present application to
have dopaminergic effects. . . . Compounds having similar substituents to
the R2 substituents recited for the claimed compounds have been shown to
have dopamine receptor activity.” (Id. at ¶13, citing papers by Zhang et al.)
“I would also expect analogous activity for the treatment of diseases
involving dopamine receptors. . . . it is my opinion that one skilled in the art
would have been enabled to make and use the claimed compounds and
pharmaceutical compositions to treat diseases such as Parkinson, psychosis,
Huntington’s, impotence, renal failure, heart failure or hypertension, without
undue experimentation. (Id.)
Principles of Law
“The scope of enablement . . . is that which is disclosed in the
specification plus the scope of what would be known to one of ordinary skill
without undue experimentation.” National Recovery Technols. Inc. v.
Magnetic Separation Sys., Inc., 166 F.3d 1190, 1195-96 (Fed Cir. 1999).
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When rejecting a claim under the enablement requirement of
section 112, the PTO bears an initial burden of setting forth a
reasonable explanation as to why it believes that the scope of
protection provided by that claim is not adequately enabled by
the description of the invention provided in the specification of
the application; this includes, of course, providing sufficient
reasons for doubting any assertions in the specification as to the
scope of enablement. If the PTO meets this burden, the burden
then shifts to the applicant to provide suitable proofs indicating
that the specification is indeed enabling.

In re Wright, 999 F.2d 1557, 1561-62 (Fed. Cir. 1993).
Factors to be considered in determining whether a disclosure
would require undue experimentation . . . include (1) the
quantity of experimentation necessary, (2) the amount of
direction or guidance presented, (3) the presence or absence of
working examples, (4) the nature of the invention, (5) the state
of the prior art, (6) the relative skill of those in the art, (7) the
predictability or unpredictability of the art, and (8) the breadth
of the claims.

In re Wands, 858 F.2d 731, 737 (Fed. Cir. 1988).
“While every aspect of a generic claim certainly need not have been
carried out by an inventor, or exemplified in the specification, reasonable
detail must be provided in order to enable members of the public to
understand and carry out the invention.” Genentech Inc. v. Novo Nordisk
A/S, 108 F.3d 1361, 1366 (Fed. Cir. 1997).
Analysis
In the Appeal Brief, Lundbeck does not single out any particular claim
for separate consideration. The same is true in the Reply Brief. A Rule 132
Declaration of Benny Bang-Andersen also treats the claims as a whole.
Accordingly, we will decide the enablement issue on the basis of Claim 4.
37 C.F.R. § 41.37(c)(1)(vii)(2009).
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While the Examiner analyzes the Wands factors in the Answer, we
have not found a corresponding analysis in the Appeal Brief or Reply Brief.
Rather it appears that Lundbeck relies on the Bang-Andersen Declaration
testimony to demonstrate error on the part of the Examiner.
The Examiner made specific findings of fact. While Lundbeck
broadly maintains in the Reply Brief (page 8) “that the factual record of this
case does not establish that the claimed subject matter fails to meet the test
of enablement,” Lundberg does not address in the Reply Brief the specific
facts found by the Examiner. We proceed with an analysis of the Wands
factors in the order the Examiner placed them, followed by an analysis of the
Bang-Andersen Declaration testimony.
(1) Breadth of the claims
Claim 4 covers many compounds. We have not calculated the number
of compounds because some of the members of the R2 Markush group have
an indefinite number of possibilities. For example R2 can be arylalkyl with
no limit on the number of carbon atoms, the number of aryl groups or the
number of alkyl groups on the aryl groups. Another example is the
heteroarylalkyl having 1 to 3 carbon atoms in the alkyl moiety. The
heteroaryl portion of the Markush group member is open to an unlimited
number of possibilities. Also open to unlimited possibilities are the possible
“can be substituted” on the aryl/heteroaryl nucleus. The breadth of Claim 4
has a definite appearance of Lundberg attempting to preempt the field
without providing enablement commensurate in scope with the breadth of
Claim 4.
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(2) Nature of the invention
The Examiner finds that the invention is a chemical compound said to
be a prodrug.
(3) State of the prior art
(a) The Examiner first notes that drugs and enzymes react in a lock and
key mechanism and that the structure of a compound has to be specific.
(Ans. 6.) What we think the Examiner means is that drugs and enzymes
function in what is known as a “lock and key mechanism” and that in order
to function in a lock and key mechanism, the structure of a compound has to
be specific as to a particular enzyme.
To make her point, the Examiner notes that a difference in a methyl
group [―CH3] versus a hydrogen [―H] can change “the properties
altogether.” The Examiner calls attention to theophylline versus caffeine.
N
H
N
O
O
H3C
CH3
Theophylline
N
N
O
O
H3C
CH3
CH3

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Caffeine
Theophylline differs from caffeine by a methyl versus hydrogen, but
only one (theophylline) has a pharmaceutical use as a bronchodilator.
Accordingly, the Examiner reasons that there is no absolute
predictability that similar compounds would “behave in the exact same
way.” What we think the Examiner meant was that there is no reasonable
expectation that similar compounds necessarily would have the same use or
the same degree of usefulness.
(b) The Examiner also found that there is no established correlation
between in vitro activity and the treat of diseases in vivo as the in vitro data
is not a reliable predictor of success even in view of the seemingly high level
of skill in the art. (Ans. 6.) On this basis, the Examiner found that one
skilled in the art would not necessarily accept any therapeutic regimen on
the face of a prediction.
(c) The Examiner found that finding a prodrug is an empirical exercise.
For example, the Examiner stated that predicting whether a certain ester of a
claimed alcohol is in fact a prodrug that produces the active compound
metabolically in man at a therapeutic concentration and at a useful rate is
filled with experimental uncertainty. In other words, experimentation would
be necessary to determine whether an ester prodrug in fact metabolizes to an
alcohol drug in the body.
The Examiner found that for a compound to be a prodrug, it must
meet three tests. Test 1: the prodrug is biologically inactive. Test 2: the
prodrug must be metabolized in the body to a second substance (the drug) at
a rate and to an extent to produce a drug at a physiologically meaningful
concentration. Test 3: the metabolized drug must be clinically effective.
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Relying on the literature, the Examiner notes that determining whether
a particular compound meets these three criteria in a clinical trial setting
requires a large quantify of experimentation. Wolfe outlines a research
program needed to be undertaken to develop a new prodrug. (Wolfe 976,
col. 1.) In § 10, Wolfe also reveals that there are substantial difficulties
facing one skilled in the art attempting to develop a prodrug. (Id. at 967-
977.) Wolfe is consistent with Banker which states that “extensive
development must be undertaken” to find a prodrug. (Banker 596.)
(4) Level of skill in the art
The Examiner found that “[t]he ordinary artisan is highly skilled.”
(Ans. 6.) We are not entirely sure what the Examiner means by “highly
skilled.” However, Dr. Benny Bang-Andersen says that he is a person
skilled in the art. (Decl. ¶ 2.) Dr. Bang-Andersen has a Ph.D. degree and
claims considerable experience in the field. (Decl. ¶¶ 2-3.) While degrees
and experience are not irrelevant, they are not particularly helpful per se in
determining the level of skill in the art. Argyropoulos v. Swarup,
56 USPQ2d 1795, 1807 (BPAI 2000). The Examiner found that the
Declaration is presented by a person highly skilled in the art. (Ans. 18.)
The examiner goes on to say, however, that it is the person having ordinary
skill who must not have to engage in undue experimentation. Matching the
Examiner's finding that the person having ordinary skill “is highly skilled”
with Dr. Bang-Andersen’s credentials, we find that Dr. Bang-Andersen is a
person having ordinary skill in the art.
(5) Level of predictability in the art
The Examiner found, and Lundbeck has not explicitly disagreed, that
the pharmaceutical art is unpredicatable.
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The Examiner first addressed “how to use.” (Ans. 7.) The Examiner
found that the pharmaceutical art is unpredictable requiring each
embodiment to be individually assessed for physiological activity.
Lundberg does not deny the accuracy of the Examiner's finding. Precedent
supports the proposition that the degree of enablement is inversely
proportional to the unpredictability—particularly where broad claims are
asserted. In re Fisher, 427 F.2d 833, 839 (CCPA 1970).
Apart from some rather broad assertions in the Specification
concerning potential utility of the compounds of Claim 4, the only
pharmacology example relates to experimental data said to have been
conducted with respect to behavioral testing of rats with “Compound
GMC6650.” (See Spec., col. 24:8-34.)
The Examiner next addressed “how to make.” The Examiner quoted a
passage from Dorwald, disclosing that “many attempted syntheses fail,” and
that synthetic research chemists “spend most of their time working out what
went wrong, and why.” (Ans. 7.) Based on Dorwald, the Examiner found
“it is not very easy to synthesize compounds.” (Id.) Although “easy” is not
the standard for undue experimentation, Dorwald’s disclosure indicates that
most syntheses are the result of years of work, and “the final synthesis
usually looks quite different from that originally planned, because of
unexpected difficulties encountered in the initially chosen synthetic
sequence.” (Id.)
(6) Amount of direction provided by the inventor
The Examiner found the Specification taught how to prepare one
compound wherein m is 2 and R2 is propyl, provided no starting materials
for compounds having other than R2 as propyl, and showed no test data that
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the compounds treat a disease. (Ans. 8.) The compound that was made is
said to be a derivative of formula Ia, not the elected If compound. (Id.) The
Examiner found it significant that there are no definitions for various groups
named in the claims, namely, haloalkyl, arylalkyl, heteroarylalkyl. The
Examiner found that “it would require undue experimentation to find out
which compound would behave as a prodrug.” (Id.)
(7) Existence of working examples
The Examiner found there were no working examples and “no data
provided that the compounds do treat any disease, which in itself is a tedious
and highly experimental task.” (Ans. 8-9.)
(8) Quantity of experimentation needed to make or use the invention
The Specification provides general assurances that the claimed
compounds may be made, but provides little specific guidance. The
Examiner found that Wolff and Banker evidenced that extensive empirical,
i.e. trial-and-error, experimentation is required to find working pro-drugs.
We agree that Wolff and Banker support that finding. Dr. Bang-Anderson
does not discuss the Wolff and Banker evidence.
Dr. Bang-Anderson relies on two papers by Zhang et al. as evidencing
that substituents “similar” to those recited in the claims have dopaminergic
activity. (FF 32.) Declarant provides no explanation of what compounds in
Zhang are thought pertinent. Neither Dr. Bang-Anderson nor Lundbeck has
explained how the Zhang compounds relate to the claimed compounds and
subject matter. Lundbeck argues that “the compounds discussed in the
review articles provided by the Declarant evidence the fact that the
compounds recited in the claims have dopamine receptor activity.” (Reply
8.) No further explanation is given.
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We find the evidence supports the Examiner’s view that extensive
experimentation is required in the pro-drug field. We find the Declaration in
general agreement that the Specification provided a starting point for
experimentation. We find the Declaration unresponsive to the Wolff and
Banker evidence. There is scant factual evidence to support the Declarant’s
multiple opinions that the experimentation needed is not undue. After
weighing the evidence, we think the Examiner correctly concluded that on
this record, undue experimentation would be required to practice the
invention with the claimed scope. See Genentech Inc. v. Novo Nordisk A/S,
108 F.3d 1361, 1366 (Fed. Cir. 1997) (“[although] a specification need not
disclose what is well known in the art . . ., that general, oft-repeated
statement is merely a rule of supplementation, not a substitute for a basic
enabling disclosure. . . . It is the specification, not the knowledge of one
skilled in the art, that must supply the novel aspects of an invention in order
to constitute adequate enablement.”).
CONCLUSIONS
Recapture
The failure to prosecute linking claims is an error that may be
corrected by reissue if the linking claims could have been prosecuted in the
application from which the patent issued. The rejection of record must be
reversed because it did not explain why, under that standard, linking claims
in this reissue application could not have been prosecuted in the application
from which the patent issued.

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Enablement
The totality of the record evidence supports a conclusion that undue
experimentation would have been required to practice the scope of the
claims.
SUMMARY
We reverse the rejection of claims 1-32 under 35 U.S.C. § 251.
We affirm the rejection of claims 1, 3-4, 10, 19, 25-27 and 31-32
under 35 U.S.C. § 112, first paragraph.

No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a).

AFFIRMED-IN-PART

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