Ex Parte Pathi et al

Board of Patent Appeals and Interferences

Jul 25, 2011

11574642 (B.P.A.I. Jul. 25, 2011)

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.
11/574,642 05/23/2007 Srinivas Laxminarayan Pathi EEHC/24259US
(4137-02100)
7262
30652 7590 07/25/2011
CONLEY ROSE, P.C.
5601 GRANITE PARKWAY, SUITE 750
PLANO, TX 75024
EXAMINER
WILLIS, DOUGLAS M
ART UNIT PAPER NUMBER
1624
MAIL DATE DELIVERY MODE
07/25/2011 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 SRINIVAS LAXMINARAYAN PATHI,
RAVIKUMAR PUPPALA, RAJENDRA NARAYANRAO KANKAN,
and DHARMARAJ RAMACHANDRA RAO
__________

Appeal 2011-004075
Application 11/574,642
Technology Center 1600
__________

Before DEMETRA J. MILLS, JEFFREY N. FREDMAN, and
STEPHEN WALSH, Administrative Patent Judges.

Opinion for the Board filed by
WALSH, Administrative Patent Judge.

Opinion Concurring filed by
FREDMAN, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134(a) involving claims to a
process for the preparation of the alpha crystal form of the compound of
Formula II. The Patent Examiner rejected the claims as obvious. We have
jurisdiction under 35 U.S.C. § 6(b). We reverse.

Appeal 2011-004075
Application 11/574,642

2
STATEMENT OF THE CASE
The invention concerns a process for preparing Imatinib which is the
international non-proprietary name of 4-(4-methylpiperazin-l-yl methyl)-N-
[4-methyl-3-(4-pyridin-3-yl)pyrimidin-2-ylamino)phenyl]-benzamide.
(Spec. 1, ll. 13-14.) Imatinib is used for the treatment of patients with
certain types of leukemia and a gastro-intestinal stromal tumor. (Id. at ll. 14-
16.)
Claims 1-4, 6-8 and 34 are on appeal. Claim 1 is representative and
reads as follows:
1. A process for the preparation of the alpha crystal form of the
compound of Formula II:

II

wherein the said process comprises:
(a) suspending or dissolving the compound of the Formula I in a solvent;

I

(b) adding methane sulfonic acid at a temperature of 25°C to 30 °C to the
suspension or solution formed in step (a);
(c) heating the mixture formed in step (b) to at least 70°C for 1 to 2
hours; and
(d) cooling the mixture to ambient temperature and isolating the alpha
crystal form,
wherein the alpha crystal form is a stable crystal form of the
Appeal 2011-004075
Application 11/574,642

3
compound of Formula II, and
wherein the mixture is not concentrated prior to cooling.

The Examiner rejected the claims 1-4, 6-8 and 34 under 35 U.S.C. §
103(a) as unpatentable over Kankan.1

OBVIOUSNESS
The Issue
The Examiner’s position is that step (d) of the instant application
recites “(d)(1) cooling the mixture to ambient temperature, (2)
concentrating the mixture of step (d)-(1) to obtain a crude alpha crystal
form of Imatinib mesylate and (3) isolating the alpha crystal form of
Imatinib mesylate.” (Ans. 4-5.) The Examiner found that the “only
difference” between the instantly recited process and Kankan’s process was
that Kankan’s step (d) comprised “(1) concentrating the mixture before (2)
cooling the crude Imatinib mesylate to ambient temperature.” (Id. at 5,
emphasis added.) According to the Examiner, this difference only involved
a change in the sequence of steps, and will not support patentability. (Id. at
6.)
Appellants contend that “the Examiner’s characterization of
Appellants’ claim 1 is in error.” (App. Br. 7.) Specifically, Appellants
assert that instant “claim 1 does not recite concentration of a reaction
mixture after cooling” or at all. (Id. at 8.) According to Appellants, the

1 Patent Application Publication No. GB 2 398 565 A by Rajendra
Narayanrao Kankan et al., published Aug. 25, 2004.

Appeal 2011-004075
Application 11/574,642

4
instantly claimed process “allow[s] for the product crystals to grow in a
dilute solution,” which product is then filtered, washed and dried. (Id. at
11.)
The issue on appeal is whether the rejection was based on an
erroneous claim interpretation that led to a failure to recognize a difference
between the claimed method and the prior art method.
Findings of Fact
1. Independent claim 1 recites the following step:
(d) cooling the mixture to ambient temperature and isolating
the alpha crystal form,
wherein the alpha crystal form is a stable crystal form of the
compound of Formula II, and
wherein the mixture is not concentrated prior to cooling.

(App. Br. 13, Claims App’x.)

2. The Specification states that “[t]he isolation in step (d) may be
achieved by filtration, preferably followed by drying under reduced
pressure.” (Spec. 5, ll. 14-15.)
3. The Specification states in Example 1 that the mixture is “cooled to 25
to 30°C, filtered and washed with isopropyl alcohol, dried under reduced
pressure at 45 to 50°C to obtain 110 g of Imatinib mesylate alpha-form.”
(Id. at 10, ll. 20-26.)
4. The Examiner’s position is that step (d) of claim 1 recites:
“(1) cooling the mixture to ambient temperature, (2) concentrating the
mixture of step (d)-(1) to obtain a crude alpha crystal form of Imatinib
mesylate and (3) isolating the alpha crystal form of Imatinib mesylate.”
(Ans. 4-5.)
Appeal 2011-004075
Application 11/574,642

5
5. Neither claim 1 nor the Specification recites or describes
“concentrating the mixture of step (d).” (See, e.g., FF1, 2, and 3.)
Principles of Law
The question of obviousness is resolved on the basis of underlying
factual determinations including (1) the scope and content of the prior art,
(2) any differences between the claimed subject matter and the prior art, (3)
the level of skill in the art, and (4) where in evidence, so-called secondary
considerations. Graham v. John Deere Co., 383 U.S. 1, 17 (1966).
Analysis
We agree with Appellants that the Examiner has mischaracterized the
claimed invention by stating that step (d) of claim 1 recites “(1) cooling the
mixture to ambient temperature, (2) concentrating the mixture of step (d)-
(1) to obtain a crude alpha crystal form of Imatinib mesylate and (3)
isolating the alpha crystal form of Imatinib mesylate.” (FF4.) Instead claim
1 recites in step (d) that “the mixture is not concentrated prior to cooling.”
(FF1.) The Examiner states that “the skilled artisan in the field of chemistry
readily recognizes that obtaining any one of the individual components of
any mixture inherently involves concentrating said mixture, wherein to
concentrate means … to make less dilute or remove solvent.” (Ans. 9.) We
disagree. The claimed process does not make the mixture less dilute nor
remove solvent. Essentially, the Examiner’s position is that the mixture
becomes concentrated when the alpha crystal form is removed. However,
after the crystal is removed, what remains can no longer be called a mixture
comprising a crystal. At most, the removal of the crystal by, e.g. filtration
may be said to concentrate the crystal, i.e., the filtration product. Similarly,
while the claimed process may be interpreted as concentrating the product,
Appeal 2011-004075
Application 11/574,642

6
i.e., imatinib, by filtering the mixture (see FF2, 3), the process does not
explicitly or inherently involve “concentrating the mixture of step (d).”
(FF5.) Consequently, the rejection did not establish that the claimed
invention would have been obvious over Kankan, because it failed to
recognize that the claimed subject matter differed from the prior art by not
requiring the mixture in step (d) to be concentrated. See Graham v. John
Deere Co., 383 U.S. at 17.

CONCLUSION OF LAW
The record does not support a conclusion that Kankan’s disclosure
would have made the claimed process prima facie obvious.

SUMMARY
We reverse the rejection of claims 1-4, 6-8 and 34 under 35 U.S.C.
§ 103(a) as unpatentable over Kankan.

REVERSED
Cdc

CONCURRING OPINION
Fredman, Administrative Patent Judge
While I am constrained by the evidence of record to concur in the
Majority’s conclusion, I find the implicit reliance on the claim limitation
“wherein the mixture is not concentrated prior to cooling” troubling.

Appeal 2011-004075
Application 11/574,642

7
Additional Findings of Fact
6. When Appellants introduced the limitation “wherein the
mixture is not concentrated prior to cooling” into claim 1, in the amendment
filed Apr. 8, 2009, Appellants identify paragraph 0025 of the Substitute
Specification for support (see Applicant’s Amend., 4/8/2009).
7. Paragraph 0025 of the Substitute Specification reads, in its
entirety:
[0025] It will be noted that the alpha crystal form of imatinib
mesylate obtained by the process of the present invention
involves refluxing, followed by cooling and isolation of the
crystals. The contrasts with the process in WO99/03854,
where the process involves refluxing, cooling, filtration,
evaporation to dryness, suspension in ethanol, refluxing,
adding water, cooling and filtering the alpha form. This
much more complex process apparently produces the alpha
form in a state which is less stable and more hygroscopic
than the product produced in accordance with the process of
the present invention. It will be particularly noted that an
advantageous feature of the present invention is that water,
per se, is not added at any stage of the process.

8. There is no teaching in the Specification or Kankan of whether
the “refluxing” step will inherently result in some concentration of the
solution, but Kankan simply states that “the reaction mixture was refluxed
for 2 hours. The reaction mixture was concentrated to about 100 ml volume,
cooled and the product isolated” (Kankan 18).
Additional Principles of Law
“[I]t is the specification itself that must demonstrate possession. And
while the description requirement does not demand any particular form of
disclosure, … or that the specification recite the claimed invention in haec
verba, a description that merely renders the invention obvious does not
Appeal 2011-004075
Application 11/574,642

8
satisfy the requirement” Ariad Pharmaceuticals, Inc. v. Eli Lilly and Co.,
598 F.3d 1336, 1352 (Fed. Cir. 2010).
In Miyazaki, the Board stated:
[R]ather than requiring that the claims are insolubly
ambiguous, we hold that if a claim is amenable to two or
more plausible claim constructions, the USPTO is justified
in requiring the applicant to more precisely define the metes
and bounds of the claimed invention by holding the claim
unpatentable under 35 U.S.C. § 112, second paragraph, as
indefinite.

Ex Parte Miyazaki, 89 USPQ2d 1207, 1211 (BPAI 2008).
Analysis
In my view, the Majority opinion focuses upon the Examiner’s flawed
approach to interpreting concentration,2 without addressing underlying
issues such as a concern that the claim limitation “wherein the mixture is not
concentrated prior to cooling” represents new matter.
I reach that conclusion after review of paragraph 0025 of the
substitute Specification, which provides no support, suggestion, or teaching
that mixture is not concentrated prior to cooling. At best, it might be
inferred that such a step is not necessary or that the absence of such a step is
obvious, but there is no clear possession of a method which deliberately
excludes a concentration step (see FF 7).
The next issue is how the phrase “wherein the mixture is not
concentrated prior to cooling” should be interpreted. Claim 1 does not state

2 I agree with Majority that the Examiner’s approach to the term
“concentration” is flawed.
Appeal 2011-004075
Application 11/574,642

9
that the mixture is “refluxed” for 1 to 2 hours, but rather states “heating the
mixture formed in step (b) to at least 70ºC for 1 to 2 hours” (see Claim 1).
Any heating step, including a reflux step, will necessarily result in the loss of
some solvent.3 Consequently, I would address whether the claim is
indefinite since the heating step will necessarily result in a concentration of
the mixture, a result which is directly contradicted by the negative limitation.
However, with regard to the art as applied to the claims as they
currently stand, I am constrained to agree with the Majority that Kankan
expressly teaches a concentration step, a step which is expressly excluded by
the negative limitation of claim 1.

3 See, e.g.,
http://us.mt.com/global/en/home/supportive_content/supportive_information
/knowledge_base/XT_Reflux_Efficiency.rxHgAwXLlLnPBMDSzq--
.MediaFileComponent.html/XT_Reflux_Efficiency.pdf for more
information.