Ex Parte Reddy et al

Patent Trial and Appeal Board

Sep 21, 2012

10601844 (P.T.A.B. Sep. 21, 2012)

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.
10/601,844 06/23/2003 Manne Satyanarayana Reddy BULK 3.0-018 9550
45776 7590 09/24/2012
DR. REDDY''S LABORATORIES, INC.
200 SOMERSET CORPORATE BLVD
SEVENTH FLOOR
BRIDGEWATER, NJ 08807-2862
EXAMINER
WARD, PAUL V
ART UNIT PAPER NUMBER
1624
MAIL DATE DELIVERY MODE
09/24/2012 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 PATENT TRIAL AND APPEAL BOARD
__________

Ex parte MANNE SATYANARAYANA REDDY, SRINIVASAN
THIRUMALAI RAJAN, UPPALA VENKATA BHASKARA RAO, and
VADDADI PATTABHI RAMAYYA
__________

Appeal 2012-000207
Application 10/601,844
Technology Center 1600
__________

Before TONI R. SCHEINER, ERIC GRIMES, and STEPHEN WALSH,
Administrative Patent Judges.

GRIMES, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to an
antihistamine, which the Examiner has rejected for indefiniteness,
anticipation, and obviousness. We have jurisdiction under 35 U.S.C. § 6(b).
We affirm-in-part, but designate the affirmance a new ground of rejection.
STATEMENT OF THE CASE
“Cetirizine and its salts, including dihydrochloride, is known and is
effective in the treatment of allergies. . . . Antihistamines, such as cetirizine,
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block the effect of histamines.” (Spec. 2.) “‘[C]etirizine’ is a generic term
that denotes the racemic mixture of R and S enantiomers” (id. at 7). “The R
enantiomer is referred to as levocetirizine” (id.). “Levocetirizine is believed
to have a two-fold higher affinity for human H1 receptors than cetirizine.
Levocetirizine is believed to be rapidly and extensively absorbed.
Levocetirizine also has been shown to be free from side effects on the
central nervous system.” (Id. at 3.)
Claims 1-18 are on appeal. Claims 1 and 2 are representative and read
as follows:
1. Amorphous levocetirizine dihydrochloride.

2. Amorphous levocetirizine dihydrochloride, which is substantially
free of crystalline forms of cetirizine dihydrochloride.

The claims stand rejected as follows:
• Claims 2 and 10 under 35 U.S.C. § 112, second paragraph (Answer
4);
• Claims 1-16 under 35 U.S.C. § 102(b) as anticipated by each of
Tang,1 Pflum,2 and Van de Venne3 (Answer 5); and
• Claims 17 and 18 under 35 U.S.C. § 103(a) as obvious based on
Van de Venne (Answer 8).

1 Tang Xiang-hong, et al., Enantomeric Separation of Cetirizine
Hydrochloride by HPLC, 22(4) J. CHINA PHARM. UNIV. 311-312 (2002).
2 Derek A. Pflum et al., A Large-Scale Synthesis of Enantiomerically Pure
Cetirizine Dihydrochloride Using Preparative Chiral HPLC, 5 ORGANIC
PROCESS RESEARCH & DEVLOP.110-115 (2001).
3 Van de Venne et al., US 6,489,329 B2, Dec. 3, 2002.
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I.
The Examiner has rejected claims 2 and 10 as indefinite, on the basis
that “‘substantially’ . . . is a relative term, which renders the claim[s]
indefinite. The term ‘substantially’ is not defined by the claim[s], the
specification does not provide a standard for ascertaining the requisite
degree, and one of ordinary skill in the art would not be reasonably apprised
of the scope of the invention.” (Answer 4-5.)
Appellants argue that the Specification defines what is meant by
“substantially free of crystalline forms,” as recited in claims 2 and 10
(Appeal Br. 4, Reply Br. 6).
We agree with Appellants that the phrase “substantially free of
crystalline forms” does not make claims 2 and 10 indefinite. The
Specification states that “the term ‘substantially free of crystalline forms of
cetirizine dihydrochloride,’ as used herein, means that the crystalline form of
cetirizine dihydrochloride cannot be detected by methods known to those
skilled in the art” (Spec. 7). The Examiner has not provided persuasive
reasoning to support his conclusion that the use of “substantially” in this
phrase renders claims 2 and 10 indefinite despite the Specification’s express
definition. The rejection under 35 U.S.C. § 112, second paragraph, is
reversed.
II.
The Examiner has rejected claims 1-16 as anticipated by each of Tang
and Van de Venne (Answer 5). The Examiner finds that “Tang teaches the
levocetirizine dihydrochloride and falls within the range of Applicant’s
compounds” (id.) and that “Van de Venne teaches compositions comprising
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levocetirizine dihydrochloride with one or more pharmaceutically acceptable
excipients, and falls within the range of Applicant’s compounds” (id. at 6).
The Examiner has also rejected claims 17 and 18 as obvious based on
Van de Venne, because, although “[t]he claims differ from the reference by
reciting the composition containing a moisture content . . . one skilled in the
art would find the differences in the teaching to be negligible” (id. at 8).
Appellants argue that “[a]lthough the English portions of Tang
apparently disclose an isolation of levocetirizine hydrochloride by high
performance liquid chromatography, there is no teaching or suggestion that
the isolated levocetirizine hydrochloride was in a solid form, or was
amorphous” (Appeal Br. 4). Appellants also argue that while “Van de
Venne . . . discloses compositions comprising levocetirizine dihydrochloride
with one or more pharmaceutically acceptable excipients, . . . there is no
teaching or suggestion that the levocetirizine dihydrochloride was
amorphous” (id. at 5). Appellants argue that Van de Venne does not
describe how its levocetirizine dihydrochloride was made, so it would be
improper for the Examiner to shift the burden to them to show that it is not
amorphous (Reply Br. 10).
We agree with Appellants that the Examiner has not provided an
adequate basis for finding that Tang and Van de Venne disclosed amorphous
levocetirizine dihydrochloride. As Appellants point out, Tang describes
separation of the enantiomers of cetirizine dihydrochloride, but does not
describe the separated enantiomers as amorphous, or even as solid.
Van de Venne discloses pharmaceutical compositions comprising “an
effective amount of (i) pseudoephedrine . . . and an effective amount of (ii)
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at least one compound selected from 2-[4-(diphenylmethyl)-1-piperazinyl]-
acetic acid or amide derivatives” (Van de Venne, col. 2, l. 64 to col. 3, l. 1).
“The most preferred compounds (ii) are the racemate . . known as cetirizine
dihydrochloride, and its levorotatory and dextrorotatory enantiomers” (id. at
col. 4, ll. 36-40).
Van de Venne discloses that its formulations can be in solid form (id.
at col. 5, ll. 25-50) but, as Appellants point out, it does not describe them as
amorphous or describe how the enantiomers of ceterizine dihydrochloride
are isolated. The reference therefore provides insufficient evidence to
support the Examiner’s conclusion (Answer 6) that it inherently discloses
the claimed amorphous levocetirizine dihydrochloride.
We reverse the rejection of claims 1-16 as anticipated by either Tang
or Van de Venne. Because the Examiner’s obviousness rejection (Answer
8) is addressed only to the moisture content limitations of claims 17 and 18,
we also reverse the rejection of claims 17 and 18 as obvious based on Van
de Venne.
III.
Issue
The Examiner has rejected claims 1-16 as anticipated by Pflum, on the
basis that Pflum inherently discloses the amorphous form of levocetirizine
dihydrochloride (Answer 5-7). The claims have not been argued separately
and therefore stand or fall together. 37 C.F.R. § 41.37(c)(1)(vii).
Appellants contend that Pflum “does not teach or suggest that the
resulting levocetirizine dihydrochloride was amorphous” (Appeal Br. 5).
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The issue with respect to this rejection is: Does the evidence provide
an adequate basis for shifting the burden to Appellants to show that Pflum’s
levocetirizine dihydrochloride was not amorphous?
Findings of Fact
1. Pflum discloses enantiomerically pure ceterizine dihydrochloride
(Pflum 110, title).
2. Pflum refers to racemic cetirizine dihydrochloride as “(±)-1” (id. at
110, Fig. 1).
3. Pflum describes a process of making the (R) form of compound 1;
i.e., the R form of cetirizine dihydrochloride, or levocetirizine dihydro-
chloride (id. at 114, right col., last full ¶; Spec. 7).
4. Pflum states that HCl was added to a solution of a precursor
compound (“(R)-2”), then
the reaction mixture was distilled to remove the methanol as it
formed. The organic phase was removed, and to the aqueous
phase was added methyl ethyl ketone (MEK, 70 L total).
Azeotropic removal of water . . . provided a slurry of (R)-1 in
MEK which was filtered, washed with MEK (5.5 kg), and dried
to furnish the title compound (1.2 kg, 74%) with >99% purity.
(Pflum 114, right col., last full ¶.)
5. The Specification exemplifies the following method of making
amorphous levocetirizine dihydrochloride:
Levocetirizine dihydrochloride (10.0 grams) was dissolved in a
mixture of acetone (40 ml) and water (100 ml). The reaction
mixture was stirred at a temperature of 25-35°C to get a clear
solution. The reaction solution was then filtered and the solvent
was completely distilled off from the reaction solution to
dryness . . . to result [in] the amorphous form of levocetirizine
dihydrochloride.
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(Spec. 16 (Example 4).)
Principles of Law
Where . . . the claimed and prior art products are identical or
substantially identical . . . the PTO can require an applicant to
prove that the prior art products do not necessarily or inherently
possess the characteristics of his claimed product. . . . [The]
fairness [of the burden-shifting] is evidenced by the PTO’s
inability to manufacture products or to obtain and compare
prior art products.
In re Best, 562 F.2d 1252, 1255 (CCPA 1977).
“[W]hen the PTO shows sound basis for believing that the products of
the applicant and the prior art are the same, the applicant has the burden of
showing that they are not.” In re Spada, 911 F.2d 705, 708 (Fed. Cir. 1990).
Analysis
Claim 1 is directed to “[a]morphous levocetirizine dihydrochloride”
and therefore reads on any amount of levocetirizine dihydrochloride, in the
amorphous form. See SmithKline Beecham Corp. v. Apotex Corp., 403 F.3d
1331, 1339 (Fed. Cir. 2005) (claim to crystalline paroxetine hydrochloride
hemihydrate “encompasses, without limitation, PHC hemihydrate – a crystal
form of paroxetine hydrochloride that contains one molecule of bound water
for every two molecules of paroxetine hydrochloride in the crystal
structure”).
Pflum discloses a method of making solid levocetirizine dihydro-
chloride that is very similar to the method described in the Specification’s
Example 4. Both methods include a solution of levocetirizine dihydro-
chloride in a mixture of water and a ketone solvent – Pflum’s because the
levocetirizine dihydrochloride results from conversion of the corresponding
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methyl ester (“(R)-2”) and the Specification’s because levocetirizine
dihydrochloride was directly dissolved in the mixed solvents. In Pflum’s
method the water is removed to provide a slurry of (precipitated)
levocetirizine dihydrochloride, which is then filtered out of the remaining
solvent and dried, while in the Specification’s method the solvent is distilled
off completely to yield dried levocetirizine dihydrochloride. Both methods,
therefore, separate the solid levocetirizine dihydrochloride from the solvent
mixture.
In addition, it is noteworthy that Pflum does not characterize its (R)-1
product as crystalline but does characterize another product as “crystallized”
(compare Pflum 114, right col., middle and last full ¶¶). The fact that Pflum
noted the crystalline nature of some products, but not its (R)-1 product,
provides further evidence that the solid (R)-1 was not crystalline, and
therefore amorphous. Cf. Spec. 3-4 (distinguishing between the amorphous
form of a drug and crystalline forms).
We conclude that the similarity between Pflum’s method of making
levocetirizine dihydrochloride and the Specification’s Example 4, describing
a method of making amorphous levocetirizine dihydrochloride, provides an
adequate basis for concluding that Pflum disclosed amorphous levocetirizine
dihydrochloride even though it did not characterize it as such. Pflum’s
characterization of some products, but not (R)-1, as crystalline supports this
conclusion. Thus, the burden is properly shifted to Appellants to provide
evidence that carrying out the process disclosed by Pflum does not result in
amorphous levocetirizine dihydrochloride.
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Conclusion of Law
The evidence provides an adequate basis for shifting the burden to
Appellants to show that Pflum’s levocetirizine dihydrochloride was not
amorphous.
SUMMARY
We reverse the rejection under 35 U.S.C. § 112, second paragraph,
and the prior art rejections based on Tang and Van de Venne.
We affirm the rejection of claims 1-16 as anticipated by Pflum.
However, since our reasoning differs significantly from the Examiner’s, we
designate the affirmance a new ground of rejection to give Appellants a fair
opportunity to respond to the reasoning that we rely on.
TIME PERIOD FOR RESPONSE
This decision contains a new ground of rejection pursuant to 37 CFR
§ 41.50(b) (effective September 13, 2004, 69 Fed. Reg. 49960 (August 12,
2004), 1286 Off. Gaz. Pat. Office 21 (September 7, 2004)). 37 CFR §
41.50(b) provides "[a] new ground of rejection pursuant to this paragraph
shall not be considered final for judicial review."
37 CFR § 41.50(b) also provides that the appellants, WITHIN TWO
MONTHS FROM THE DATE OF THE DECISION, must exercise one of
the following two options with respect to the new ground of rejection to
avoid termination of the appeal as to the rejected claims:
(1) Reopen prosecution. Submit an appropriate
amendment of the claims so rejected or new evidence relating
to the claims so rejected, or both, and have the matter
reconsidered by the examiner, in which event the proceeding
will be remanded to the examiner. . . .
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(2) Request rehearing. Request that the proceeding be
reheard under § 41.52 by the Board upon the same record. . . .

AFFIRMED-IN-PART, 37 C.F.R. § 41.50(b)

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