Ex Parte Holmaas et al

Board of Patent Appeals and Interferences

Aug 20, 2010

10560497 (B.P.A.I. Aug. 20, 2010)

MOD PTOL-90A (Rev.06/08)

APPLICATION NO./
CONTROL NO.
FILING DATE FIRST NAMED INVENTOR /
PATENT IN REEXAMINATION
ATTORNEY DOCKET NO.
10/560,497 12/12/2005 Lars Terje Holmaas et al.

EXAMINER
KATAKAM, SUDHAKAR
ART UNIT PAPER NUMBER
GE HEALTHCARE, INC.
IP DEPARTMENT 101 CARNEGIE CENTER
PRINCETON, NJ 08540-6231

1621
MAIL DATE DELIVERY MODE

08/23/2010 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.

UNITED STATES DEPARTMENT OF COMMERCE
U.S. Patent and Trademark Office
Address : COMMISSIONER FOR PATENTS
P.O. Box 1450
Alexandria, Virginia 22313-1450
www.uspto.gov
UNITED STATES PATENT AND TRADEMARK OFFICE
_____________________________________________________________________________________
UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte LARS TERJE HOLMAAS, OLE MAGNE HOMESTAD,
JAN CERVENKA, and KHALID HUSSAIN
__________

Appeal 2010-000515
Application 10/560,497
Technology Center 1600
__________

Before DONALD E. ADAMS, DEMETRA J. MILLS, and MELANIE L.
McCOLLUM, Administrative Patent Judges.

McCOLLUM, Administrative Patent Judge.

DECISION ON APPEAL1
This is an appeal under 35 U.S.C. § 134 involving claims to an
iohexol production process. The Examiner has rejected the claims as
obvious. We have jurisdiction under 35 U.S.C. § 6(b). We affirm.

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.
Appeal 2010-000515
Application 10/560,497

2
STATEMENT OF THE CASE
Claims 1-21 are pending and on appeal (App. Br. 1). The claims have
not been argued separately and therefore stand or fall together. 37 C.F.R.
§ 41.37(c)(1)(vii). We will focus on claim 1, which reads as follows:
1. A process for the production of iohexol comprising alkylating
5-(acetamido)-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophtalamide
with a 2,3-dihydroxypropylating agent in the presence of a base and of a
solvent which solvent comprises a C1-C5-monoalkylether of a C3-C10
alkylene-glycol.
Claims 1-21 stand rejected under 35 U.S.C. § 103(a) as obvious in
view of Malthe-Sorensen et al. (US 5,948,940, Sep. 7, 1999) (Ans. 4).
The Examiner relies on Malthe-Sorensen for teaching “a process for
the production of iohexol, said process comprising reacting 5-(acetamido)-
N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodoisophtalamide with a
2,3-dihydroxypropylating agent in the presence of a base and a solvent, viz.,
2-methoxy-ethanol . . . [,] which is a C1-C5-monoalkylether of a C2-C10
alkylene-glycol” (Ans. 4). The Examiner concludes that it would have been
obvious “to have modified the reference’s teachings by using an alternative
solvent, such as 1-methoxy-2-propanol with a reasonable expectation of
success” (id. at 5). In support of this position, the Examiner finds that the
“solvents differ by one carbon” and, relying on In re Henze, 181 F.2d 196
(CCPA 1950), “note[s] that adjacent homologs are considered to be obvious
absent unexpected results” (id.).
ISSUE
Does the evidence support the Examiner’s conclusion that it would
have been obvious to modify the iohexol production process disclosed in
Malthe-Sorensen to use a solvent comprising 1-methoxy-2-propanol?
Appeal 2010-000515
Application 10/560,497

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FINDINGS OF FACT
1. The Specification discloses that “WO-A-02/083623 discloses
the purification of crude iohexol using 1-methoxy-2-propanol as the solvent
optionally in a mixture with other solvents” (Spec. 2).
2. Malthe-Sorensen discloses “a process for the production of
iohexol . . . comprising reacting 5-acetamido-N,N'-bis(2,3-dihydroxy-
propyl)-2,4,6-triiodophthalamide with a 2,3-dihydroxypropylating agent in
the presence of a solvent . . . compris[ing] 2-methoxy-ethanol and,
optionally, isopropanol” (Malthe-Sorensen, col. 2, ll. 1-7).
3. Malthe-Sorensen also disclose that “[t]he reaction solvent
preferably is 2-methoxy-ethanol; however a mixture of 2-methoxy-ethanol
and isopropanol may be used, e.g. up to 95 vol % isopropanol may be used”
(id. at col. 2, ll. 39-42).
4. Malthe-Sorensen also discloses that the process “is preferably
effected in the presence of a base” (id. at col. 2, ll. 53-54).
5. In addition, Malthe-Sorensen discloses:
The crude iohexol obtained . . . may then be purified preferably
by recrystallization.
In the method of the invention, the crude iohexol starting
material . . . is first dissolved in the crystallization solvent. In
one particularly preferred embodiment, the solution used may
simply be the reaction mixture from the process of the
invention, optionally after adjustment of its salt content, with
the isopropanol/2-methoxy-ethanol content of the solvent if
necessary also being adjusted.
(Id. at col. 3, ll. 11-22.)
6. In a Rule 132 Declaration, one of the inventors states: A
different homolog, 2-ethoxyethanol, was initially considered, but “was
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Application 10/560,497

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impossible to use . . . due to solubility and selectively. 1-methoksy-2-
pronanol [sic] (PM) was not considered since it was estimated to be even
less polar than 2-ethoxyethanol.” (Decl. 1.)2
7. The Rule 132 Declaration also states:
To be able to use a solvent in the alkylation step it is necessary
that NaOH is soluble. . . . Regarding PM, NaOH was not
soluble. . . . At first a modification of PM by adding co-solvents
for increasing solubility of NaOH was not considered due to the
assumption that such an addition would worsen selectivity of
the reaction. This is true for 2-ME. It was therefore definitely
not obvious to pursue this lead any further.
(Id. at 1-2.)
8. In addition, the Rule 132 Declaration states: “In summary it
was not believed that PM was able to substitute 2-ME. This assumption was
based on decades of experience with these processes and general chemical
knowledge.” (Id. at 2.)
PRINCIPLES OF LAW
Obviousness analysis “need not seek out precise teachings directed to
the specific subject matter of the challenged claim.” KSR Int’l Co. v.
Teleflex Inc., 550 U.S. 398, 418 (2007). Instead, it proper to “take account
of the inferences and creative steps that a person of ordinary skill in the art
would employ.” Id. “A person of ordinary skill is also a person of ordinary
creativity, not an automaton.” Id. at 421.
Structural relationships may provide the requisite motivation or
suggestion to modify known compounds to obtain new
compounds. For example, a prior art compound may suggest

2 The page citations are to the Declaration as filed on July 14, 2008, rather
than the reformatted version submitted with the Appeal Brief.
Appeal 2010-000515
Application 10/560,497

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its homologs because homologs often have similar properties
and therefore chemists of ordinary skill would ordinarily
contemplate making them to try to obtain compounds with
improved properties.
In re Deuel, 51 F.3d 1552, 1558 (Fed. Cir. 1995).
“[A]ll disclosures of the prior art, including unpreferred embodiments,
must be considered.” In re Lamberti, 545 F.2d 747, 750 (CCPA 1976).
A reference may be said to teach away when a person of
ordinary skill, upon reading the reference, would be
discouraged from following the path set out in the reference, or
would be led in a direction divergent from the path that was
taken by the applicant. The degree of teaching away will of
course depend on the particular facts; in general, a reference
will teach away if it suggests that the line of development
flowing from the reference’s disclosure is unlikely to be
productive of the result sought by the applicant.
In re Gurley, 27 F.3d 551, 553 (Fed. Cir. 1994).
“An assertion of what seems to follow from common experience is
just attorney argument and not the kind of factual evidence that is required to
rebut a prima facie case of obviousness.” In re Geisler, 116 F.3d 1465, 1470
(Fed. Cir. 1997). However, “[i]f a prima facie case is made in the first
instance, and if the applicant comes forward with reasonable rebuttal,
whether buttressed by experiment, prior art references, or argument, the
entire merits of the matter are to be reweighed.” In re Hedges, 783 F.2d
1038, 1039 (Fed. Cir. 1986). “Appellant’s opinion on the ultimate legal
issue is not evidence in the case. . . . [However,] some weight ought to be
given to a persuasively supported statement of one skilled in the art on what
was not obvious to him.” In re Lindell, 385 F.2d 453, 456 (CCPA 1967).
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ANALYSIS
Malthe-Sorensen discloses “a process for the production of iohexol
. . . comprising reacting 5-acetamido-N,N'-bis(2,3-dihydroxy-propyl)-2,4,6-
triiodophthalamide with a 2,3-dihydroxypropylating agent in the presence of
a solvent . . . compris[ing] 2-methoxy-ethanol” and a base (Findings of Fact
(FF) 2 & 4). We agree with the Examiner that it would have been prima
facie obvious to replace 2-methoxy-ethanol with an adjacent homolog,
1-methoxy-2-propanol.
Appellants argue, however, that Malthe-Sorensen “does not teach,
describe, or suggest using any other solvent other than 2-methoxy-ethanol”
(App. Br. 3). We are not persuaded. Instead, we agree with the Examiner
that the structural relationship between 2-methoxy-ethanol and 1-methoxy-
2-propanol provides the suggestion to use 1-methoxy-2-propanol rather than
2-methoxy-ethanol. See In re Deuel, supra.
Appellants also argue:
[I]t was known from WO02/083623, as discussed in the present
specification, page 2, lines 1-2, to use 1-methoxy-2-propanol as
solvent in the purification by recrystallization of iohexol.
The fact that a solvent is known for its use as the dominant
solvent in the crystallisation step of the same process would
clearly teach away from using the same in the alkylation step.
(App. Br. 4.) We are not persuaded.
Claim 1 requires that the solvent comprise a C1-C5-monoalkylether of
a C3-C10 alkylene-glycol. It does not exclude the presence of a co-solvent,
as taught by Malthe-Sorensen (FF 2-3), or even require that the predominant
solvent is a C1-C5-monoalkylether of a C3-C10 alkylene-glycol. In addition,
as recognized by Appellants, Malthe-Sorensen describes “using 2-methoxy-
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ethanol as a solvent in both the alkylation and in the purification step” (App.
Br. 5; see also FF 2 & 5). We also note that Appellants’ argument is based
on attorney argument and “not the kind of factual evidence that is required to
rebut a prima facie case of obviousness.” In re Geisler, supra. Thus, we
cannot agree that the evidence of record teaches away from using the same
solvent in both steps.
In addition, Appellants argue that the Declaration of one of the
inventors demonstrates that using 1-methoxy-2-propanol would not have
been obvious (App. Br. 5-6). We are not persuaded.
The Declaration states that “it was not believed that [1-methoxy-
2-propanol] was able to substitute [2-methoxy-ethanol]” (FF 8). In addition,
the Declaration provides reasons for this belief (FF 6-7). However, on
balance, we do not agree that this evidence is sufficient to demonstrate that
one of ordinary skill in the art would not have found it obvious to replace, in
the production of iohexol, 2-methoxy-ethanol, which was known to be used
as a solvent in both the production and purification of iohexol (FF 2 & 5),
with an adjacent homolog thereof, 1-methoxy-2-propanol, which was known
to be used as a solvent in the purification of iohexol (FF 1). In this regard,
we note that, contrary to the indication in the Declaration that Appellants did
not consider adding co-solvents “due to the assumption that such an addition
would worsen selectivity of the reaction” (FF 7), Malthe-Sorensen
specifically discloses the use of a co-solvent in the production of iohexol
(FF 2-3), albeit in a non-preferred embodiment. However, “all disclosures
of the prior art, including unpreferred embodiments, must be considered.”
In re Lamberti, supra.
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Application 10/560,497

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CONCLUSION
The evidence supports the Examiner’s conclusion that it would have
been obvious to modify the iohexol production process disclosed in Malthe-
Sorensen to use a solvent comprising 1-methoxy-2-propanol.
TIME PERIOD FOR RESPONSE
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

cdc

GE HEALTHCARE, INC.
IP DEPARTMENT 101 CARNEGIE CENTER
PRINCETON, NJ 08540-6231