Ex Parte 7148211 et al

Board of Patent Appeals and Interferences

Mar 28, 2012

95001245 (B.P.A.I. Mar. 28, 2012)

UNITED STATES PATENT AND TRADEMARKOFFICE
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.
95/001,245 10/13/2009 7148211 03851.000600.36 5540
5514 7590 03/29/2012
FITZPATRICK CELLA HARPER & SCINTO
1290 Avenue of the Americas
NEW YORK, NY 10104-3800
EXAMINER
HUANG, EVELYN MEI
ART UNIT PAPER NUMBER
3991
MAIL DATE DELIVERY MODE
03/29/2012 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 BOARD OF PATENT APPEALS
AND INTERFERENCES
____________

COBREK PHARMACEUTICALS, INC.
Requester and Respondent

v.

Patent of GENZYME CORPORATION
Patent Owner and Appellant
____________

Appeal 2012-002710
Reexamination Control 95/001,245
Patent 7,148,211 B2
Technology Center 3900
____________

Before RICHARD E. SCHAFER, ROMULO H. DELMENDO, and
RICHARD M. LEBOVITZ, Administrative Patent Judges.

DELMENDO, Administrative Patent Judge.

DECISION ON APPEAL

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Patent 7,148,211 B2
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Genzyme Corporation (hereinafter “Genzyme”), the Patent Owner,
appeals from the Examiner’s final decision to reject claims 1-16 in the
above-identified inter partes reexamination of United States Patent
7,148,211 B2 (hereinafter “the ’211 Patent”).1, 2 Cobrek Pharmaceuticals,
Inc. (hereinafter “Cobrek”) is the sole Third-Party Requester.3 We have
jurisdiction under 35 U.S.C. §§ 6, 134, and 315.
We AFFIRM.

STATEMENT OF THE CASE
We have been informed that the ’211 Patent is or has been the subject
of several United States district court proceedings, including a patent
infringement action against Cobrek. App. Br. 1. We have not been made
aware, however, of any court rulings that may affect our decision.
We heard oral arguments from Genzyme on February 15, 2012. A
written transcript of the oral arguments was entered into the electronic
record on March 7, 2012.4

1 The ’211 Patent issued to Richard B. Mazess, Jeffrey W. Driscoll,
Creighton Reed Goldensoph, and Leon W. LeVan on December 12, 2006,
based on Application 10/247,765 filed September 18, 2002. We refer to the
Specification of the ’211 Patent as “Spec.”
2 See Examiner’s Answer mailed September 8, 2011, hereinafter “Ans.”;
Right of Appeal Notice mailed September 10, 2010.
3 In a Decision on Petition mailed July 13, 2011, the Chief Administrative
Patent Judge held that Cobrek’s Respondent Brief filed January 26, 2011
remains not entered. Decision on Petition mailed July 13, 2011 at 8.
4 Cobrek’s Request for Oral Hearing was denied. Decision on Petition at 8.
Therefore, Cobrek’s counsel was present at the Hearing but did not
participate in the oral arguments.
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The invention of the ’211 Patent relates to a parenteral formulation
comprising, inter alia, a lipophilic drug in the form of doxercalciferol, also
known as 1α-hydroxyvitamin D2, which may be useful in the treatment
and/or prophylaxis of a wide variety of conditions and disorders. Spec. col.
3, ll. 35-37; col. 9, ll. 29-42; col. 10, ll. 22-58. The ’211 Patent explains that
vitamin D compounds are known to be sensitive to oxygen, losing their
integrity upon oxidation. Spec. col. 3, ll. 15-17. According to Inventor
Leon W. LeVan, certain prior art antioxidants “rapidly developed yellow
color in the presence of air” and/or “did not adequately maintain
doxercalciferol potency.” Decl. (C) of Leon W. LeVan, App. Br., Evid.
App’x, Ex. C, ¶¶ 5-10; Spec. col. 3, ll. 19-22. According to the ’211 Patent,
the “invention provides a pharmaceutical formulation that overcomes the
problems associated with parenteral formulations of lipophilic drugs.” Spec.
col. 3, ll. 35-37.
Claim 1 is illustrative of the subject matter on appeal and is
reproduced as follows:
1. A parenteral formulation, comprising a lipophilic drug
which is doxercalciferol, a non-ionic solubilizer which is
polysorbate 20 present at a concentration of about 0.05% to
about 5% w/w, a lipophilic antioxidant which is butylated
hydroxytoluene (BHT) present at a concentration of about 20 to
about 2000 ppm, an optional agent which is ethanol present at a
concentration of 0 to 30% w/w, and an aqueous vehicle.
App. Br. 36, Claims App’x.

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The Examiner rejected the claims under 35 U.S.C. § 103(a) as
follows:
I. Claims 1, 2, 5, and 7 as unpatentable over HECTOROL®
Injection Package Insert5 and/or Physician’s Desk
Reference (PDR)6 in view of Hesse ’957 (hereinafter
“Hesse I”),7 Makino,8 Aiello,9 and Wade;10
II. Claims 1-16 over HECTOROL® Injection Package Insert
and/or PDR in view of Hesse ’957, Makino, Aiello,
Wade, and Hesse ’928 (hereinafter “Hesse II”);11

5 The record includes several different versions of documents entitled
“HECTOROL®” or “HECTOROL INJECTION®.” It appears, however, that
the Examiner relied on “Hectorol Injection: BCI Draft Version, March 29,
2000,” Bone Care Int’l, Inc. (exact publication date unknown), which is
identified as “Ex. E” in the Request for Inter Partes Reexamination filed
October 13, 2009. Ans. 7; Req. for Inter Partes Reexamination 2, 19-27.
Genzyme did not dispute the Examiner’s finding that HECTOROL®
Injection Package Insert is a printed publication that is available as prior art
against the appealed claims.
6 Physician’s Desk Reference® 988-990 (55th ed. exact publication date
unknown). Genzyme did not dispute the Examiner’s finding that PDR is a
printed publication that is available as prior art against the appealed claims.
7 United States Patent 5,472,957 issued to Robert H. Hesse et al. on
December 5, 1995.
8 United States Patent 5,182,274, issued to Yuji Makino et al. on January
26, 1993.
9 United States Patent 3,384,545, issued to Ronald Eugene Aiello et al. on
May 21, 1968.
10 Handbook of Pharmaceutical Excipients 7-9, 47, 48 (Ainley Wade and
Paul J. Weller eds., 2d ed., 1994).
11 United States Patent 3,901,928, issued to Robert Henry Hesse et al. on
August 26, 1975.
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III. Claims 1-16 over HECTOROL® Injection Package Insert
and/or PDR in view of ROCALTROL® Package Insert,12
Makino, Aiello, Wade, Hesse I, and Hesse II; and
IV. Claims 1-6 over HECTOROL® Injection Package Insert
and/or PDR in view of Knutson,13 Makino, Aiello, Wade,
Hesse I, and Hesse II.

DISCUSSION
REJECTION I – CLAIMS 1, 2, 5, & 7
Genzyme has argued claims 1, 2, 5, and 7 together. App. Br. 3-26.
Accordingly, we select claim 1 as representative and confine our discussion
to this selected claim. Claims 2, 5, and 7 stand or fall together with claim 1.
See 37 C.F.R. § 41.67(c)(1)(vii).
The Examiner found that the HECTOROL® Injection Package Insert
or PDR describes an injection solution of doxcercalciferol. The Examiner
acknowledged that the disclosure of the HECTOROL® Injection Package
Insert or PDR differs from the subject matter of claim 1 in that
HECTOROL® contains 10 mg of sodium ascorbate as an antioxidant rather
than the recited BHT in the specified concentration. Ans. 8. The Examiner
concluded, however, that “it would have been obvious for one of ordinary
skill in the art to substitute the sodium ascorbate in Hectorol Injection with
the alternative BHT” in view of the teachings in the other references –
namely Hesse ’957, Makino, Aiello, and Wade. Ans. 8-9.

12 ROCALTROL® Brand of Calcitriol: Capsules and Oral Solution, Roche
Laboratories, Inc. (exact publication date unknown).
13 PCT Publication WO 02/06218 A2 published on January 24, 2002.
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Genzyme contends that “the art is unpredictable . . . and there has
been no showing of a reasonable expectation of success that one would have
been able to formulate a stable, non-yellowing, aqueous parenteral
formulation of doxercalciferol . . . .” App. Br. 5. Genzyme also relies on
secondary considerations including unexpected results, failure of others, and
copying. App. Br. 17-26.
Thus, the issues arising from these contentions are:
(1) Did the Examiner identify a reason supported by sufficient
evidence that would have prompted a person of ordinary skill in the art to
substitute BHT for sodium ascorbate, thus arriving at a parenteral
formulation encompassed by claim 1?
(2) If so, did Genzyme demonstrate secondary considerations of
nonobviousness sufficient to overcome the Examiner’s prima facie case of
obviousness?
We answer Question (1) in the affirmative and Question (2) in the
negative. Our reasons follow.

The Teachings of HECTOROL® Injection:
HECTOROL® Injection Package Insert as listed in the PDR describes
an aqueous injectable (i.e., a parenteral) formulation, wherein each mL of
the aqueous formulation contains:
2 mcg (μg) doxercalciferol;
4 mg TWEEN® Polysorbate 20;
1.5 mg sodium chloride;
10 mg of sodium ascorbate;
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7.6 mg of dibasic sodium phosphate;
1.8 mg of monobasic sodium phosphate; and
1.1 mg of disodium edetate (EDTA).
P. 1.14 The Examiner found that the sodium ascorbate described in
HECTOROL® Injection Package Insert is an antioxidant. Ans. 10. Genzyme
does not dispute this finding and, in fact, acknowledges that HECTOROL®
Injection Package Insert “discloses sodium ascorbate . . . as its antioxidant.”
App. Br. 10.

The Difference Between HECTOROL® Injection and Claim 1:
HECTOROL® Injection Package Insert differs from the subject matter
of claim 1 only in that sodium ascorbate is used as an antioxidant instead of
BHT in the recited amounts. App. Br. 10.

The Known Problems of Sodium Ascorbate Antioxidant in
HECTOROL® Injection:
The ’211 Patent itself acknowledges that certain antioxidants,
including sodium ascorbate, previously used to address the oxygen
sensitivity of vitamin D compounds “will discolor in the course of
performing their intended function.” Col. 3, ll. 15-22. Therefore, a person
of ordinary skill in the art would have known, by simple observation, that
sodium ascorbate antioxidant presents the problem of discoloration. Indeed,
Declaration (A) of Dawn R. Parks (App. Br., Evid. App’x, Ex. A) confirms

14 PDR contains the same or similar disclosure as HECTOROL® Injection
Package Insert. For brevity, we focus on HECTOROL® Injection Package
Insert, but our discussion here is equally applicable to PDR.
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that HECTOROL® Injection containing sodium ascorbate was the subject of
consumer complaints related to discoloration before the filing date of the
current invention. Parks Decl. (A) ¶ 2. According to Genzyme, “the
yellowing issue experienced with doxercalciferol formulations made with
sodium ascorbate mandated the use of a nitrogen overlay during filling of
the ampoules, as well as the maintenance of an inert gas headspace in the
filled ampoule.” App. Br. 6; Declaration (B) of Inventor Leon W. LeVan ¶
7.

Prior Art Teachings Regarding BHT Antioxidant for Vitamin D:
The relied-upon evidence reveals that BHT was well known as an
FDA-approved antioxidant for vitamin D injections that do not suffer from
discoloration.
In particular, Wade teaches that butylated hydroxytoluene (BHT) was
well known as an antioxidant in several types of compositions including
pharmaceuticals such as for injection. P. 47. According to Wade, 0.0009-
0.002% of BHT is sufficient for use as an antioxidant in IV injections. Id.
Dr. Gilbert S. Banker testified as an expert for “Third Party Requester
Pentech Pharmaceuticals, Inc.” Decl. of Gilbert S. Banker filed March 24,
2010 ¶ 1. Dr. Banker previously held the position of Head of the
Department of Industrial and Physical Pharmacy at Purdue University,
where he taught for nearly 30 years. Banker Decl. ¶ 7. In 1992, he was
named Dean and Distinguished Professor of Drug Delivery in the College of
Pharmacy at the University of Iowa, where he currently serves as an
Emeritus Professor and Dean since 1999. Id. Dr. Banker testified that it was
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known that BHT is an antioxidant that does not discolor in an aqueous
solution exposed to air. Banker Decl. ¶ 14. According to Dr. Banker, BHT
was approved by the FDA for use in a wide range of oral, rectal, vaginal,
topical, and injectable dosage forms. Banker Decl. ¶ 16.
Makino teaches:
[W]hen an aqueous preparation of 1α, 25-
dihydroxycholecarciferol [sic, 1α, 25-dihydroxycholecalciferol
– an active form of vitamin D3] was provided by insolubilizing
the compound from water at a pH ranging from 6.4 to 7.8 with
a nonionic surface active agent and stabilizing it with a
combination of a metal salt of ascorbic acid and disodium
edetate to provide an aqueous preparation, and the storage test
was conducted in ampules, it was found to be susceptible to
heat and cause such a level of yellowing as it may happen in
high possibility in the usual distribution process of medical and
pharmaceutical products. [Emphases added.]
Col. 2, ll. 47-57. Thus, Makino teaches that the combination of a nonionic
surface active agent, sodium ascorbate (a metal salt of ascorbic acid), and
EDTA rendered an aqueous formulation containing a compound that is
structurally similar to doxercalciferol susceptible to heat and subject to
yellowing at certain pH values. Specifically, Makino attributes the problems
to the use of EDTA as a chelating agent. Col. 3, l. 33 to col. 4, l. 9. Makino
states that “an aqueous preparation of active form of vitamin D3 which is
resistant to discoloration and stable even in the presence of oxygen can be
produced by solubilizing the active form of vitamin D3 with a nonionic
surface active agent and adding a combination of at least one of chelating
agents selected from the group consisting of citric acid, tartaric acid and
their metal salts with an antioxidant . . . .” (emphasis added). Col. 2, l. 62 to
col. 3, l. 3. Furthermore, Makino teaches that the preparations may be
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parenteral solutions for intravenous injection. Col. 5, ll. 33-35. Although
Makino teaches that sodium ascorbate may be used as the antioxidant, it also
exemplifies the use of BHT in a working example directed to an oral
composition. Col. 4, ll. 40-49; col. 8, ll. 21-59 (Example 5). With respect to
the nonionic surface active agent, Makino teaches the use of TWEEN® 20,
the same polysorbate 20 used in the claimed invention. Makino at col. 4, ll.
21-31and col. 6, ll. 27-42; ’211 Patent at col. 8, l. 51 to col. 9, l. 7 and col.
11, ll. 41-65.
In a working example, Aiello describes an aqueous parenteral
composition containing, inter alia, vitamin D2 (calciferol), BHT, and
Emulphor EL-620 (an emulsifying agent that is a polyoxyethylene ether of
castor oil). Col. 5, l. 61 to col. 6, l. 12 (Example 5). Aiello characterizes the
composition as an aqueous emulsion. Dr. Banker, however, testified that
HECTOROL® Injection, which is characterized as an “aqueous solution,” is
“not an aqueous solution” but rather “. . . an aqueous micellar colloidal
dispersion containing micelles that contain doxercalciferol, which is a
concept akin to an emulsion.” Banker Decl. ¶ 18.
Hesse I teaches, in addition to oral compositions, a parenteral
composition containing, inter alia, vitamin compounds such as active
vitamin D2 and “an antioxidant such as ascorbic acid, butylated
hydroxyanisole, butylated hydroxytoluene [BHT] or hydroquinone.” Col. 2,
ll. 24-48.

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The Combination of the Prior Art References:
In view of the collective teachings of the prior art references, we agree
with the Examiner that a person of ordinary skill in the art would have found
it obvious to substitute BHT for sodium ascorbate in the HECTOROL®
Injection based on the reasonable expectation that they would be
interchangeable as antioxidants when used to stabilize parenteral
composition containing doxercalciferol. KSR Int’l Co. v. Teleflex, Inc., 550
U.S. 398, 416 (2007) ( “[W]hen a patent claims a structure already known in
the prior art that is altered by the mere substitution of one element for
another known in the field, the combination must do more than yield a
predictable result.”) (citation omitted).
Because a person of ordinary skill in the art would have readily
known that (1) the HECTOROL® Injection containing sodium ascorbate and
EDTA was susceptible to yellowing, thus requiring the use of nitrogen and
(2) the use of FDA-approved BHT alone or BHT in combination with a
specified chelating agent other than EDTA (in compositions containing
structurally similar vitamin D compounds) does not suffer from the problem
of yellowing, a person of ordinary skill in the art would have had ample
reason to modify the HECTOROL® Injection in the manner claimed. KSR,
550 U.S. at 417 (“When a work is available in one field of endeavor, design
incentives and other market forces can prompt variations of it, either in the
same field or a different one . . . . [I]f a technique has been used to improve
one device, and a person of ordinary skill in the art would recognize that it
would improve similar devices in the same way, using the technique is
obvious unless its actual application is beyond his or her skill.”). See also In
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re Mayne, 104 F.3d 1339, 1343 (Fed. Cir. 1997) (“Structural relationships
often provide the requisite motivation to modify known compounds to
obtain new compounds.”) (citation omitted).
“When the PTO shows prima facie obviousness, the burden then shifts
to the applicant[s] to rebut.” Mayne, 104 F.3d at 1342 (citation omitted).
Genzyme appears to be arguing that to support an obviousness
conclusion, the prior art must teach the same purpose contemplated by the
inventors. App. Br. 4 (“a person of ordinary skill in the art would not have
had any reasonable expectation of success in solving the problems
associated with the Hectorol® injection product containing sodium ascorbate
by substituting BHT therefor.”). Genzyme is incorrect on this matter. See
KSR, 550 U.S. at 419 (“In determining whether the subject matter of a claim
is obvious, neither the particular motivation nor the avowed purpose of the
patentee controls. What matters in the objective reach of the claims.”).
Hesse I, Makino, Aiello, and Ward all show that FDA-approved BHT
may be successfully used as an antioxidant in similar vitamin D parenteral
compositions and thus a person of ordinary skill in the art would have
reasonably expected that BHT would provide the same or similar antioxidant
effect for doxercalciferol parenteral formulations, which is a formulation
containing a vitamin D analog. Even in the unpredictable arts, only a
reasonable expectation of success – not absolute predictability – is required
to support a conclusion of obviousness. In re O’Farrell, 853 F.2d 894, 904
(Fed. Cir. 1988).
Indeed, Makino explicitly teaches that the use of an antioxidant such
as BHT or sodium ascorbate and a specified chelating agent (citric acid,
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tartaric acid and their metal salts) instead of sodium ascorbate and EDTA
chelating agent, which are present in the problematic HECTOROL®
Injection, provides a stable composition that is “resistant to discoloration,”
even in the presence of oxygen. Col. 2, l. 62 to col. 3, l. 3; Example 5; Table
5. Thus, a person of ordinary skill in the art would have had specific
motivation to modify HECTOROL® Injection by using BHT and citric acid,
tartaric acid or their metal salts in lieu of sodium ascorbate and EDTA. In
this regard, we emphasize that Claim 1 reads on a doxercalciferol
formulation that contains BHT and a chelating agent such as tartaric acid salt
but which does not contain EDTA.
While Genzyme makes much of the fact that Makino’s Example 5
showing the use of BHT is directed to an oral aqueous preparation (App. Br.
12), it failed to direct us to persuasive evidence that the antioxidizing effect
of BHT would be significantly and unpredictably different in a parenteral
composition relative to an oral composition. In any event, Makino plainly
teaches parenteral injectable compositions as well. Col. 5, ll. 33-35. Also,
while Genzyme refers to Makino’s Table 1 as evidence that Makino’s
formulation containing sodium ascorbate and trisodium citrate dihydrate
turned yellow (“a little yellowish” or “pale yellow”) despite the use of
nitrogen, it did not direct us to persuasive evidence that BHT and trisodium
citrate dihydrate yielded a result that is unexpectedly better than sodium
ascorbate and trisodium citrate dehydrate.
Genzyme contends that Aiello requires the use of glycerine and a
polyoxyethylene ether of castor oil and is directed to parenteral
compositions for animals and poultry, not humans. App. Br. 13. Therefore,
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according to Genzyme, “Aiello would not have provided any guidance to a
person of ordinary skill to substitute BHT for sodium ascorbate with a
reasonable expectation that the problems of the prior art formulation, i.e.,
Hectorol® Injection Package Insert and/or PDR, could be overcome. . . . .”
Id. These contentions have no merit. First, claim 1 does not exclude
glycerine. In fact, the ’211 Patent identifies glycerine (glycerol) as an
optional additional agent to enhance the solubility of the lipophilic
therapeutic agent in the carrier system. Col. 9, ll. 14-28. Second, while
Aiello describes the use of a polyoxyethylene ether of castor oil as an
emulsifying agent, it is similar (in terms of its ability to emulsify lipophilic
drugs in water) to TWEEN® 20 disclosed in HECTOROL® Injection. That
finding is consistent with the disclosure in the ‘211 Patent itself that
TWEEN® and polyethoxylated castor oil are alternative solubilizers. Col. 8,
l. 51 to col. 9, l. 7. Third, nothing in the claim 1 recites that the parenteral
formulation is limited to those suitable for humans. In fact, ’211 Patent
plainly states that the claimed formulation “has utility in the treatment or
prevention of diseases or disorders affecting mammals, including humans . .
. .” (emphasis added). Col. 4, ll. 22-34.
Relying on Declaration (C) of Inventor LeVan (¶¶ 4-7), Genzyme
argues that “[i]n a side by side testing of seven different antioxidants in
fourteen different formulations, BHT was the only antioxidant that led to a
stable, non-yellowing, aqueous parenteral formulation of doxercalciferol
when combined with Tween 20 and water.” App. Br. 16. But Inventor
LeVan’s testing merely shows the screening of a limited number of known
antioxidants options to determine the best antioxidant to solve a known
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problem (yellowing). The testing or work performed to determine which of
the known FDA-approved antioxidants would solve the discoloring problem
has not been shown to involve anything beyond the ordinary and routine
skill in the art. A person of ordinary skill in the art, having knowledge that
HECTOROL® Injection suffered from discoloration, would have looked to
solutions reported in other literature, including Makino, which explicitly
discloses that BHT and a particular chelating agent is resistant to
discoloration. KSR, 550 U.S. at 421 (“When there is a design need or
market pressure to solve a problem and there are a finite number of
identified, predictable solutions, a person of ordinary skill has good reason
to pursue the known options within his or her technical grasp.”).
Also, notwithstanding Genzyme’s argument that the aqueous
formulation containing BHT antioxidant and vitamin D2 of Aiello’s Example
5 is an oral composition, it would reasonably appear that the same person of
ordinary skill would have also learned, by simple observation, that Aiello’s
exemplified aqueous formulation provides a clear, stable formulation and
thus would have found it obvious to implement the improvement in
HECTOROL Injection to address its discoloration problem. In re Baxter
Travenol Labs., 952 F.2d 388, 392 (Fed. Cir. 1991) (“Mere recognition of
latent properties in the prior art does not render nonobvious an otherwise
known invention . . . . Since the prior art bags plasticized with DEHP were
inherently suppressing hemolysis, albeit unknown at the time of the Becker
document, this hemolysis-suppressing function is not a basis for rebutting a
prima facie finding of obviousness.”) (internal citation omitted).
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For similar reasons, Genzyme’s arguments based on unexpected
results and processing advantages are equally unpersuasive. App. Br. 17-20.
While we have fully considered the evidence offered, we think that a person
of ordinary skill in the art would have pursued known antioxidant options,
including Makino’s BHT and tartaric acid salt combination that is said to be
“resistant to discoloration” or Aiello’s BHT antioxidant to address the
known problem of yellowing attributed to the combination of sodium
ascorbate and EDTA. Again, the testing of a limited number of known
antioxidants commonly used for vitamin D parenteral formulations and then
evaluating that data do not rise to the kind of unexpected results required to
overcome a strong prima facie case of obviousness. Asyst Techs., Inc. v.
Emtrak, Inc., 544 F.3d 1310, 1316 (Fed. Cir. 2008) (“[E]vidence of
secondary considerations does not always overcome a strong prima facie
showing of obviousness.”).
Genzyme is correct that the relied-upon evidence shows that sodium
ascorbate does not function in an identical manner to BHT. App. Br. 11, 18;
LeVan Decl. (D) ¶¶ 4-12. That showing, however, is limited to formulations
that contain EDTA chelating agent. But claim 1 does not require EDTA. As
discussed above, Makino indicates that when EDTA is replaced with a
different chelating agent such as tartaric acid salt, the use of an antioxidant
such as sodium ascorbate or BHT provides a formulation that is free from
the discoloration problem. Also, while Inventor LeVan states that the
claimed formulation “unexpectedly has improved stability over time,” we
agree with the Examiner’s finding (Ans. 34-35) that Genzyme failed to offer
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a side-by-side test showing that BHT is unexpectedly better than sodium
ascorbate in terms of potency over time.
Genzyme further contends that others attempted but failed to solve the
problem of discoloration. App. Br. 20-21. That contention is contradicted
by the disclosure of Makino, which solved the same or similar problem for a
closely related compound (active vitamin D3).
Genzyme asserts that five entities, including Cobrek, have copied the
invention. App. Br. 24. Specifically, Genzyme argues that each of these
entities filed an Abbreviated New Drug Application (ANDA) that includes a
paragraph IV certification for the ’211 Patent. Id. Genzyme’s unsupported
assertion amounts to mere attorney argument and is therefore ineffective.
We have not been directed to persuasive, specific evidence that these entities
in fact copied, infringed, and sold or intend to sell the invention. Wyers v.
Master Lock Co., 616 F.3d 1231, 1246 (Fed. Cir. 2010). Moreover, “[n]ot
every competing product that arguably falls within the scope of a patent is
evidence of copying; otherwise, ‘every infringement suit would
automatically confirm the nonobviousness of the patent.’” Iron Grip Barbell
Co., Inc. v. USA Sports, Inc., 392 F.3d 1317, 1325 (Fed. Cir. 2004). It is
equally plausible that copyists did so upon concluding that the ’211 Patent
claims were too broad to escape the reach of prior art and therefore invalid.
The short answer here is that Genzyme did not produce the type of evidence
that would be considered sufficient to demonstrate that the copying was due
to the merits of the invention.
For these reasons, we uphold Rejection I.

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REJECTION II – CLAIMS 1-16
Genzyme has argued the claims in three groups as follows: (i) claims
1, 2, 5, and 7; (ii) claims 3, 4, 6, and 8-16; and (iii) claims 9 and 16. App.
Br. 26-30. Regarding group (i), Genzyme relies on the same arguments
offered against Rejection I. Therefore, we find them unpersuasive for the
same reasons stated above. As to groups (ii) and (iii), we select claims 3 and
9, respectively, as representative and confine our discussion to these selected
claims.

Claim 3:
Claim 3 is reproduced below:
3. A [formulalion] formulation as set forth in claim 1,
wherein the optional agent is present in a concentration of about
1% to about 3% w/w.
The Examiner’s position is that Hesse I, Hesse II, Makino, and Wade
all suggest the incorporation of ethanol into HECTOROL® Injection. Ans.
11.
Genzyme argues that “the only composition example in Hesse II is an
oral composition” and that “the oral composition provided in the example of
Hesse II does not contain ethanol.” App. Br. 28.
Thus, the sole issue15 raised is:

15 Genzyme has not offered any reasonably specific arguments against the
Examiner’s reliance of Hesse I, Makino, and Wade with respect to the
limitation recited in claim 3. Therefore, apart from arguments already
addressed, we consider that Genzyme has waived any argument against the
Examiner’s reliance of these references as to claim 3.
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(3) Does Hesse II provide a reason for a person of ordinary skill in
the art to incorporate a suitable amount of ethanol into HECTOROL®
Injection?
We find no error in the Examiner’s rejection based on the
combination of HECTOROL® Injection and Hesse II. Hesse II teaches:
In general, 1α-hydroxy-25-hydrogen vitamin D
compounds and 1α-hydroxy-9,10-tachysterol may be
administered parenterally in combination with an injectable
liquid carrier such as sterile pyrogen-free water, sterile
peroxide-free ethyl oleate, dehydrated alcohol, propylene glycol
or a dehydrated alcohol/propylene glycol mixture. Such
compositions may be injected intravenously, intraperitoneally
or intramuscularly. Injectable compositions are preferably
prepared in dosage unit form, e.g. in ampoules, each unit
advantageously containing 0.1-200 μg, preferably containing
0.2-20 μg of the active vitamin ingredient in the case of the
vitamin D2 and D2 compounds
. . . .
Col. 7, ll. 32-45 (emphases added).
Thus, Hesse II plainly teaches the use of dehydrated alcohol, which
includes dehydrated ethanol, in parenteral formulations. Genzyme appears
to believe that a prior art disclosure should be ignored unless it is in the form
of a working example. That is incorrect. It is well established that a
reference is good for all it fairly teaches a person having ordinary skill in the
art, even a when the teaching is a cursory mention. E.g., In re Mills,
470 F.2d 649, 651 (CCPA 1972).
For these reasons, we find no error in the Examiner’s rejection of
claim 3.

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Patent 7,148,211 B2
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Claim 9:
Claim 9, which ultimately depends from independent claim 7 through
intervening claim 8, recites the further limitation that “the parenteral
formulation has been terminally sterilized.”
The Examiner construed this limitation as a “product-by-process”
limitation. Ans. 43. The Examiner found that HECTOROL® Injection is a
sterile product and therefore the limitation does not confer patentability.
Ans. 12.
Genzyme argues that HECTOROL® Injection does not mention
terminal sterilization and therefore “cannot teach or suggest a parenteral
formulation that is terminally sterilized.” App. Br. 28.
Thus, the issue raised is:
(4) Did Genzyme show that a processing step of terminal
sterilization on HECTOROL® Injection results in a new and unobvious
product?
We agree with the Examiner. The patentability of a claimed product
rests on the product made, not by the process by which the product is made.
In re Thorpe, 777 F.2d 695, 697 (Fed. Cir. 1985).
In this case, it is undisputed that HECTOROL® Injection is a sterile
product. Genzyme failed to direct us to persuasive evidence that terminal
sterilization of HECTOROL® Injection as modified by the teachings of the
other references to include BHT in lieu of sodium ascorbate imparts any
difference. Therefore, Genzyme’s argument fails.

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Patent 7,148,211 B2
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REJECTION III – CLAIMS 1-16
To the extent that Genzyme repeats arguments already made against
Rejections I and II, these arguments are unpersuasive for the reasons given
above.
Genzyme’s other arguments focus solely on ROCALTROL® Package
Insert. According to Genzyme, ROCALTROL® Package Insert constitutes
“evidence of the unpredictable nature of the art relating to formulation of
vitamin D analogs” because it requires a combination of BHA (butylated
hydroxyanisole) and BHT antioxidants. App. Br. 31. Genzyme further
contends that ROCALTROL® Package Insert is exclusively directed to oral
compositions. App. Br. 32.
Even if we accept Genzyme’s characterizations of the reference as
correct, neither argument is persuasive. As pointed out by the Examiner
(Ans. 44), claim 1 recites “comprising” (open language) and therefore does
not exclude BHA or other materials.
Regarding the argument that ROCALTROL® Package Insert is
directed to an oral composition, the Examiner is relying on the collective
teachings of the prior art references, with ROCALTROL® Package Insert
providing further evidence of the use of BHT as an antioxidant. Ans. 13, 32.

REJECTION IV – CLAIMS 1-16
To the extent that Genzyme repeats arguments already made against
Rejections I through III, these arguments are unpersuasive for the reasons
given above.
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Patent 7,148,211 B2
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Genzyme focuses its argument on Knutson, emphasizing that
Knutson’s discloses oral compositions. App. Br. 32-35. We simply refer to
the Examiner’s treatment of Genzyme’s argument against Knutson.
In any event, Knutson is cumulative to the other references.
Therefore, we affirm this rejection for the same reasons that we affirmed
Rejections I through III.

DECISION
The Examiner’s decision to reject claims 1-16 is affirmed.
Requests for extensions of time in this inter partes reexamination
proceeding are governed by 37 C.F.R. § 1.956. See 37 C.F.R. § 41.79.

AFFIRMED

rvb

Patent Owner:

FITZPATRICK CELLA HARPER & SCINTO
1290 AVENUE OF THE AMERICAS
NEW YORK, NY 10104-3800

Third-Party Requester:

ROBERT S. SILVER
CAESAR RIVISE BERSTEIN COHEN & POKOTILOW LTD
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