Ex Parte Kong et al

Patent Trial and Appeal Board

Oct 31, 2016

12842990 (P.T.A.B. Oct. 31, 2016)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR
12/842,990 07/23/2010
20350 7590 11/02/2016
KILPATRICK TOWNSEND & STOCKTON LLP
Mailstop: IP Docketing - 22
1100 Peachtree Street
Suite 2800
Atlanta, GA 30309
Xianqi Kong
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
ATTORNEY DOCKET NO. CONFIRMATION NO.
95256-000llOUS-864221 5199
EXAMINER
ZUCKER, PAUL A
ART UNIT PAPER NUMBER
1671
NOTIFICATION DATE DELIVERY MODE
11/02/2016 ELECTRONIC
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.
Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the
following e-mail address( es):
ipefiling@kilpatricktownsend.com
j lhice@kilpatrick.foundationip.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte XIAN QI KONG, DAVID MIGNEAULT, and XINFU WU1
Appeal2015-001486
Application 12/842,990
Technology Center 1600
Before JACQUELINE WRIGHT BONILLA, ULRIKE W. JENKS, and
DEVON ZASTROW NEWMAN, Administrative Patent Judges.
NEWMAN, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving a claim to a purity-
enhanced pharmaceutical drug candidate free of bromide. The Examiner has
entered final rejections of anticipation and obviousness. We have
jurisdiction under 35 U.S.C. § 6(b ).
We affirm.
STATEMENT OF THE CASE
The Specification discloses "[t]his invention pertains to methods of
preparation of sulfonate derivatized compounds, e.g., 3-amino-1-
propanesulfonic acid and 1,3-propanedisulfonic acid disodium salt with
increased purity, with reduced potential for toxic by-products, and that are
1 Appellants identify the Real Party in Interest as Kiacta Sarl. App. Br. 3.
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Application 12/842,990
pharmaceutically useful, e.g., for the treatment of amyloidosis. Spec. 11 :32-
35. "[An] aspect [of] the invention is directed to a purity-enhanced
pharmaceutical drug candidate comprising: 1,3-propanedisulfonic acid or a
salt thereof, wherein the pharmaceutical drug candidate is free of bromide."
Id. at 11 :3-6.
The following issues are before us on review (Ans. 3-5):
A. Claim 185 is rejected under 35 U.S.C. § 102(b) as anticipated
by Zuffanti2 or Kisilevsky.3
B. Claim 185 is rejected under 35 U.S.C. § 103(a) as obvious over
Zuffanti or Kisilevsky.
Claim 185 is the sole claim on appeal and reads as follows:
185. A purity-enhanced pharmaceutical drug candidate comprising:
1,3-propanedisulfonic acid or a salt thereof,
\"/herein the pharmaceutical drJg candidate is free of bromide.
App. Br. Claims Appendix 15.
ANTICIPATION
Issue
The issue is: Does the preponderance of evidence of record support
the Examiner's finding that Zuffanti or Kisilevsky teach the composition of
claim 18 5?
2 Saverio Zuffanti and Rudolf Hendrickson, The Preparation of Some
Alkane-a,w-disulfonic Acids, 63 JOURNAL OF THE AMERICAN CHEMICAL
SOCIETY, 2999-3000 (1941) ("Zuffanti")
3 Robert Kisilevsky et al., WO 96/28187 Al, published Sept. 19, 1996
("Kisilevsky")
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Application 12/842,990
Findings ofFact
FF 1. The Specification states:
The language "free of" is used herein, in reference to a final
product of a sulfonate derivatized compound, e.g., a
pharmaceutical drug candidate, i.e., derived from a crude or
purified reaction mixture, which is completely lacking a
referenced item, for example, a byproduct (such as bromide),
which has been introduced into the reaction through the
synthetic process. For example, in certain embodiments, the
language "free of' is not intended to encompass impurities, for
example, residual sodium, which has been introduced through
environmental factors rather than through the synthetic process.
Spec. 17:14-20.
FF 2. The Specification states:
The language "purity-enhanced" is used in reference to a final
product of a sulfonate derivatized compound, e.g., a
pharmaceutical drug candidate, i.e., derived from a crude or
purified reaction mixture, e.g., including, but not limited to the
sulfonate derivatized compounds produced by the methods of
the invention, which is significantly free of byproducts, e.g.,
toxic by-products (i.e., by-products that are side-products of the
reaction or residual starting material that would be considered
unsuitable for administration to a subject, e.g., a human, or
preferentially omitted by a skilled artisan from a pharmaceutical
composition prepared for administration to a subject). It should
be noted that purity-enhanced compounds of the invention are
not intended to be limited by scale of the reaction that produces
the compounds.
Id. at 15: 14-23.
FF 2. Zuffanti discloses purification of anhydrous a,co-Decamethylene-
disulfonic acid as follows:
The acids were purified by redissolving them in a minimum of
absolute methanol and saturating the solutions with dry
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Application 12/842,990
hydrogen chloride. This procedure carried the reaction further
to completion as evidenced by the precipitation of sodium
chloride. After filtration, the acids were recovered as
previously indicated and recrystallized several times from
absolute methanol.
Zuffanti col. 2, iJ 2.
FF 3. Kisilevsky discloses that sodium 1,3-propanedisulfonate is
prepared by a modification of the method described in Stone,
... 1,3-Dibromopropane (40.4 g, 0.20 mol) was treated with
sodium sulfite (60.3 g, 0.50 mol) in water at reflux temperature
for 48 h. Inorganic salts (sodium bromide and sodium sulfite)
were removed by successive treatment of the resultant reaction
mixture with barium hydroxide and silver(l)oxide. The solution
was then neutralized with Amberlite-120 (acid form) and
decolorized with Norit-A. Barium ions were removed by
treatment of the aqueous solution with Amberlite-120 (sodium
form) ion exchange resin. The solvent was removed on a rotary
evaporator, and the crude product was recrystallized from
water-ethanol several times to give the title compound (42.5 g).
The small amount of trapped ethanol \'1/as removed by
dissolving the crystals in a minimum amount of water and then
concentrating the solution to dryness. The pure product was
further dried under high vacuum at 56 °C for 24 h ....
Kisilevsky 33:1-15.
FF 4. Kisilevsky discloses
A method for inhibiting amyloid deposition in a subject comprising
administering to the subject an effective amount of a therapeutic
compound, the therapeutic compound comprising at least one
sulfonate group covalently attached to a carrier molecule, or a
pharmaceutically acceptable salt thereof ... wherein the therapeutic
compound is ... 1,3-propanedisulfonic acid.
Id. at 34:1-13.
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Application 12/842,990
FF 5. The Barriault Declaration4 reflects the results of chromatogram
analysis of 1,3-propanedisulphonic acid, disodium salt that was prepared by
Appellants using the method ofKisilevsky. Barriault Deel. 1-2.
FF 6. The Barriault Declaration explains that "[t]he peak on both
chromatograms labeled C990 is bromide." Id. at 4.
Principles of Law
"A single prior art reference that discloses, either expressly or
inherently, each limitation of a claim invalidates that claim by anticipation."
Perricone v. Medicis Pharmaceutical Corp., 432 F.3d 1368, 1375 (Fed. Cir.
2005).
Analysis
The Examiner finds that the definition of "free of' in the Specification
(see FF 1)
does not mean that an impurity is absent but only that it has not
been introduced by the synthesis of 1, 3-propandisulfonic acid.
Any amount of any arbitrary impurity (including bromide) is
permitted as long as it has not been introduced in the synthesis
of 1, 3-propandisulfonic acid. Claim 185 therefore must be
treated as a product-by-process claim and the examiner
considers that any impurities, regardless of the amounts, in the
products of either Zuffanti or Kisilevsky are permitted by the
language "free of' when given its broadest reasonable
interpretation in light of the specification. Patentability for a
product-by-process claim is determined on the basis of the
product and not its method of formation. Claim 185 is
therefore anticipated by Zuffanti or Kisilevsky.
4 Declaration under 37 C.F.R. § 1.132 by Nancy Barriault, signed Nov. 1,
2012 ("Barriault Deel.").
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Application 12/842,990
Ans. 4.
Appellants argue neither Zuffanti or Kisilevsky "disclose any
preparation of 1,3-propanedisulfonic acid (or a salt thereof) that meets the
specific purity requirements of the present claims." App. Br. 10. Appellants
argue the Examiner incorrectly interprets "free of bromide" and that
[a] component such as bromide is clearly identified as an
unavoidable by-product of the synthesis process. In contrast,
other components which may inadvertently (and acceptably) be
present in (or added to) invention compositions are identified as
"environmental factors." Those of skill in the art readily
appreciate the difference between a reaction by-product (which
is produced as a direct consequence of the synthetic protocol
employed) as opposed to "environmental factors" (which may
vary depending on the purity of the reagents employed, the
reaction vessels employed, the methodology employed, and the
like).
Id. at 5-6.
According to Appellants, the Examiner's interpretation of the claims
is unreasonable and "[t]he purity of the claimed compositions is based on the
presence or absence of certain defined components, and not by the method
used to prepare the claimed compositions." Id. at 6.
Rejection based on Zuffanti
We find the Examiner correctly interpreted "free of' based on the
language in the Specification (FF 1 ), but do not agree with the Examiner's
position that claim 185 is a product-by-process claim. We find that claim
185 recites a composition "free of bromide" wherein "free of' means that
any bromide introduced in the synthesis process must be completely
removed. FF 1. The language "purity-enhanced" is likewise defined by the
Specification in reference to the final product, and establishes what the
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product is "free ot:" e.g., bromide. FF 2. With respect to the composition of
Zuffanti, Appellants have not identified bromide as a source in the synthesis
process or otherwise established that bromide is present in Zuffanti. Instead,
the Examiner sufficiently establishes that the composition of Zuffanti meets
the limitation of "completely lacking" bromide according to the language of
the Specification because no bromide is introduced in the synthesis process.
Ans. 4, FF 1-2. Accordingly, we find Zuffanti teaches "purity-enhanced"
1,3-propanedisulfonic acid "free of bromide" and affirm the rejection of
anticipation based on Zuffanti.
Rejection based on Kisilevsky
Kisilevsky discloses the use of 1,3-Dibromopropane (a source of
bromide) to synthesize sodium 1,3-propanedisulfonate sodium bromide.
FF 3. While sodium bromide is removed from the synthetic milieu, the
Barriault Declaration confirms that bromide is present as detected by
chromatography. FF 5-6. Accordingly, we are persuaded that Kisilevsky
does not teach "purity-enhanced" 1,3-propanedisulfonic acid "free of
bromide" and reverse the rejection of anticipation based on Kisilevsky.
Conclusion of Law
A preponderance of the evidence of record supports the Examiner's
finding that Zuffanti teaches the composition of claim 185. However, a
preponderance of the evidence of record does not support the Examiner's
finding that Kisilevsky teaches the composition of claim 185.
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OBVIOUSNESS
Issue
The issue is: Does the preponderance of evidence of record support
the Examiner's finding that Zuffanti or Kisilevsky teaches the composition
of claim 185?
The Examiner finds that:
The difference between the instantly claimed 1, 3-
propanedisulfonic acid and that taught by Zuffanti or
Kisilevsky is that Zuffanti is that a purer 1, 3-propanedisulfonic
acid is claimed ... Appellants have not demonstrated any
unexpected result or new utility for the purer form of the
compound they claim. Thus, the instantly claimed purity-
enhanced 1, 3-propanedisulfonic acid would have been obvious
to one of ordinary skill in the art.
Ans. 6-7.
Appellants argue that neither "Zuffanti nor Kisilevsky disclose or
suggest methods to produce 1,3-disulfonic acid which meet the purity
requirements of the present claims, i.e., that is free of bromide [or] provide
any motivation to produce 1,3-disulfonic acid meeting such purity
requirements. Only the present Appellants describe such methods, and
reason to do so." App. Br. 13. Appellants' cited reason for increasing purity
is "to produce preparations of 1,3-propanedisulfonic acid or a salt thereof
that met purity or quality standards sufficient for drug development
purposes; i.e., that met GMP standards or were sufficient for, e.g., the United
States FDA regulatory standards." Id., citing Garceau5 Deel., ,-i 6.
5 Declaration under 37 C.F.R. § 1.132 by Denis Garceau, signed Apr. 15,
2011 ("Garceau Deel.").
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Application 12/842,990
Appellants further argue that prior preparations of 1,3-disulfonic acid, which
they acknowledge has been "reported and known in the art for at least 65
years prior to 2003/2004" were "not suitable for clinical administration due
to the presence of synthetic by-products and other impurities." Id., citing
Garceau Deel., iJ 7.
Rejection based on Zuffanti
For the reasons given above regarding Zuffanti (FF 1-3), we find
Zuffanti anticipates and likewise also renders claim 185 obvious because it
teaches every limitation of claim 185. See In re McDaniel, 293 F.3d 1379,
1385 (Fed. Cir. 2002) (citations omitted) ("It is well settled that 'anticipation
is the epitome of obviousness"'). Accordingly, we affirm the finding of
obviousness over Zuffanti.
Rejection based on Kisilevsky
Kisilevsky discloses a method of treating amyloid deposition in a
subject comprising administering an effective therapeutic amount of 1,3-
propanedisulfonic acid or its salt. FF 4. The Examiner states "sufficient
motivation to produce pure material is found in Kisilevsky who teaches
pharmaceutical administration of 1, 3- propanedisulfonic acid as set forth in
the rejection of record. Kisilevsky also teaches 1, 3- propanedisulfonic acid
of suitable purity for administration as well as a method for producing it as
set forth in the rejection of record." Ans. 11.
While Kisilevsky teaches purification of 1,3- propanedisulfonic acid
to remove bromide, not all of the bromide used in the synthetic process is
removed as shown in the Barriault Declaration (FF 5-6). We acknowledge
that the Examiner interprets Kisilvesky' s teaching of "a pharmaceutically
acceptable salt[] ... wherein the therapeutic compound is ... 1,3-
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Application 12/842,990
propanedisulfonic acid" and the Examiner's interpretation of the
chromatogram in the Barriault Declaration to mean that the 1,3-
propanedisulfonic acid of Kisilevsky is sufficiently pure for pharmaceutical
administration. (FF 4-6) But to establish a prima facie case of obviousness,
the Examiner must articulate that the teachings of Kisilevsky would have
motivated one of skill in the art to further modify its 1,3- propanedisulfonic
acid to remove any remaining bromide, thereby arriving at the composition
of claim 185. We agree with Appellants that the Examiner has not met this
burden. Reply Br. 7-8. Accordingly, we reverse this rejection.
Conclusion of Law
A preponderance of the evidence of record does not support the
Examiner's findings that Zuffanti and Kisilevsky suggest the composition of
claim 18 5 .
SUMMARY
We affirm the rejection of claim 185 35 U.S.C. § 102(b) as anticipated
by Zuffanti.
We reverse the rejection of claim 185 35 U.S.C. § 102(b) as
anticipated by Kisilevsky.
We affirm the rejection of claim 185 under 35 U.S.C. § 103(a) as
obvious over Zuffanti.
We reverse the rejection of claim 185 under 35 U.S.C. § 103(a) as
obvious over Kisilevsky.
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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. § l.136(a).
AFFIRMED
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