Ex Parte Buck et al

Patent Trial and Appeal Board

Jun 22, 2018

12867316 (P.T.A.B. Jun. 22, 2018)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
12/867,316 11/01/2010
23117 7590 06/26/2018
NIXON & V ANDERHYE, PC
901 NORTH GLEBE ROAD, 11 TH FLOOR
ARLINGTON, VA 22203
FIRST NAMED INVENTOR
Neil Robert Buck
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.
ES-4662-163 2 9145
EXAMINER
QAZI, SABIHA NAIM
ART UNIT PAPER NUMBER
1621
NOTIFICATION DATE DELIVERY MODE
06/26/2018 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):
PTOMAIL@nixonvan.com
pair_nixon@firsttofile.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte NEIL ROBERT BUCK, WOUTER CLAERHOUT,
BRUNO H. LEUENBERGER, ELISABETH STOECKLIN,
KAI URBAN, and SWEN WOLFRAM 1
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Technology Center 1600
Before LORA M. GREEN, RICHARD M. LEBOVITZ, and
JOHN G. NEW, Administrative Patent Judges.
NEW, Administrative Patent Judge.
DECISION ON APPEAL
1Appellants identify DSM IP ASSETS B.V. as the real party-in-interest.
App. Br. 3.
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Application 12/867 ,316
SUMMARY
Appellants file this appeal under 35 U.S.C. § 134(a) from the
Examiner's Final Rejection of claims 1-3, 10, 11, 14--16, 19, and 20 as
unpatentable under 35 U.S.C. § 103(a) as being obvious over, Krammer et
al. (US 2007 /0082089 Al, April 12, 2007) ("Krammer"), Simoes-Nunes et
al. (US 2005/0064018 Al, March 24, 2005) ("Simoes-Nunes"), J.W. Blunt
et al., The Biological Activity of 25-Hydroxycholecalciferol, a Metabolite Of
Vitamin D3, 61 P.N.A.S. 1503 (1968) ("Blunt"), Bishop et al. (US
2007/0122477 Al, May 31, 2007) ("Bishop"), and R. Vieth, Vitamin D
Supplementation, 25-Hydroxyvitamin D Concentrations, and Safety, 69 AM.
J. CLIN. NUTR. 842-56 (1999) ("Veith").
We have jurisdiction under 35 U.S.C. § 6(b).
We AFFIRM.
NATURE OF THE CLAIMED INVENTION
Appellants' claimed invention is directed to the combined use of
vitamin D (cholecalciferol) and 25-hydroxyvitamin D3 ("25-0H D3") or
( calcifediol) to treat and/or prevent osteoporosis. One or more
bisphosphonate compounds to inhibit bone resorption may also be used.
Abstract.
REPRESENTATIVE CLAIM
Claim 1 is representative of the claims on appeal and recites:
1. A method of maintaining bone health, and/or
treating osteoporosis, rickets and osteopenia, comprising
administering vitamin D3 and 25-0H D3 to a human adult once
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weekly or once monthly; wherein a dosage ratio of vitamin D3
to 25-0H D3 is from 6: 1 to 1 :6.
App. Br. 14.
ISSUE AND ANALYSIS
We expressly adopt the Examiner's findings of fact and conclusion
that the claims are prima facie obvious over the combined cited prior art.
We address Appellants' arguments below.
A. Claims 1-3 and 14--16
Issue
Appellants argue these claims together. App. Br. 7. Appellants argue
that the Examiner erred in finding that the combined cited prior art
references teach or suggest all of the limitations of the claims. Id.
Analysis
The Examiner finds that Krammer teaches a method of treating or
preventing joint diseases in pets, including dogs, cats, rabbits, and pigs
comprising administering to a pet in need of such treatment or prevention an
effective amount of 25-hydroxyvitamin D3 and vitamin D3. Final Act. 4
(citing Krammer i-f 3). The Examiner finds that Krammer teaches that the
ratio of 25-0H D3 and vitamin D3 in a ratio range from 1 :9 to 9: 1 which
overlaps with the claimed range of 1:6 to 6: 1. Id.
The Examiner finds that Simoes-Nunes teaches that animal feed with
25-0H D3 in combination with vitamin D3 improves bone strength and a
reduction of locomotor disorders in animals, particularly pigs. Final Act. 7
(citing Simoes-Nunes Abstr., i-f 14). The Examiner finds Simoes-Nunes
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teaches combination of vitamin D3 and 25-0H D3 in dosage ratios which
correspond to the claimed dose ranges, specifically, approximately 10 µg/kg
to about 100 µg/kg of 25-0H D3 and from about 5 µ/kg to about 100 µg/kg
of vitamin Dare added to regular pig food. 2 Id. (citing Simoes-Nunes i-fi-f l,
5).
The Examiner finds Blunt teaches the biological activity of 25-0H D3
is approximately 1.4 times more active than vitamin D3 in curing rickets in
rats, and is also more active than the vitamin in chicks as determined via
bone ash assay. Final Act. 9-11.
The Examiner finds Bishop teaches that administration of vitamin D
supplements prevent rickets or ostomalacia. Final Act. 9 (citing Bishop i1
10). The Examiner finds Bishop teaches orally dosing a subject, an animal or
a human patient, with sufficient 25-0H D3, ergocalciferol or any
combination of these two vitamins in a formulation that provides unexpected
benefits to the recipient compared to currently available vitamin D
supplements. Id. (citing Bishop i120).
The Examiner concludes that it would have been obvious to a person
of ordinary skill in the art to prepare a combination of vitamin D3 and 25-
0H D3 for treating rickets, osteoporosis and bone health in animals,
including humans (based on the teachings of Bishop), in the dosage ranges
and ratios as claimed. Final Act. 12. The Examiner further concludes that a
2 Simoes-Nunes teaches: "In the manufacture of a pig food in accordance
with the invention, from about 10 µg/kg to about 100 µg/kg of 25-hydroxy
vitamin D3 and, if required, from about 200 IU/kg to about 4,000 IU/kg of
vitamin D3 are added to regular pig food." Simoes-Nunes i-f 5. One µg
equals 40 IU. See Krammer i1 4.
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person of ordinary skill in the art would have been motivated to select dose
ratios in the claimed range 1: 6 and 6: 1 from the direct teachings of the prior
art. Id.
Appellants argue that Krammer teaches the use of 25-0H D3, either
alone or in combination with vitamin D for use in pet food, particularly for
large or giant dogs, such as Great Danes, to prevent and treat joint diseases,
such as osteochondrosis, degenerative arthritis or arthropathy. App. Br. 7.
According to Appellants, Krammer's teaching of the use of 25-0H D3 and
vitamin D in different species, which exhibit different symptoms and possess
different typical lifespans than humans, to treat or prevent a different
condition by daily administration (and not weekly nor monthly) does not
contribute to a conclusion of obviousness. Id.
Appellants also contend that Simoes-Nunes teaches vitamins added to
a constant diet (e.g., pig feed) fed to farm animals with a limited lifespan
relative to humans. App. Br. 7-8. Appellants argue that farm animals such
as pigs display phenotypes and diseases due to inbreeding, selective
breeding, and growth and fattening in confined spaces. Id. at 8. Appellants
assert that such defects shown in pigs are not indicative of human diseases,
because humans have not undergone inbreeding and selective breeding, and
are a fast-growing and fast-fattening species relative to humans. Id.
Appellants argue, therefore, that there is no basis to assume that a diet to
counteract the effect modem animal farming practices on such animals
grown would have the same effect on humans. Id.
Appellants argue further that Blunt incorrectly teaches that 25-0H D3
represents the metabolically active form of vitamin D3, whereas BISHOP,
and other prior art, correctly teaches that 1, 25-dihydroxy vitamin D3 is the
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metabolically active form. App. Br. 8 (citing Bishop i-f 9). According to
Appellants, Blunt also teaches that the biological activity of vitamin D and
25-0H D3 is only compared with regard to their antirachitic activity (i.e.,
curing rickets) in rats. Id. Appellants contend that there is no teaching or
suggestion of a combination of vitamin D and 25-0H D3, or to a specific
dose range as claimed, or to weekly/monthly administration. Id.
With respect to Bishop, Appellants argue that the reference teaches a
pharmaceutical composition comprising vitamin D3 and/or vitamin D2 to
treat vitamin D deficiency, i.e., 25-0H D3 insufficiency or deficiency. App.
Br. 8. Appellants assert that Bishop teaches that 25-0H D3 is a pro-
hormone, which is converted into metabolically active 1, 25-dihydroxy
vitamin D3. Id. According to Appellants, Bishop teaches that vitamin D
hormones are required for normal bone formation and metabolism, however,
25-0H D3 is referred to only in a list of "other therapeutic agents" that can
be administered, depending upon the particular medical condition to be
addressed. Id. (citing Bishop i-fi-19, 11, 59). Appellants assert that there is no
teaching in Bishop that 25-0H vitamin D3 should be administered together
with vitamin D3 and/or D2 "for treating rickets and osteoporosis." Id. at 8-
9. Finally, Appellants argue, Bishop neither teaches nor suggests a dose
range ratio of 25-0H D3 to vitamin D as claimed, nor does it teach weekly
or monthly of administration. Id. at 9.
Finally, Appellants contend that Veith teaches only vitamin D
supplementation. App. Br. 9. According to Appellants, there is neither
teaching nor suggestion in Veith of combining vitamin D3 and 25-0H D3 in
a weekly or monthly treatment of osteoporosis, rickets and osteopenia, as
recited in the claims. Id.
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We are not persuaded by Appellants' arguments. As an initial matter,
Appellants are arguing the references individually, whereas it is the
teachings and suggestions of the combined prior art that form the basis of the
Examiner's rejection of the claims. See, e.g., In re Keller, 642 F.2d 413, 426
(C.C.P.A. 1981) ("[O]ne cannot show non-obviousness by attacking
references individually where ... the rejections are based on combinations of
references").
Furthermore, Bishop is directed to methods for effectively and safely
"restoring ... and maintaining blood 25-hydroxyvitamin D levels ...
include[ing] orally dosing a subject, an animal or a human patient, with
sufficient cholecalciferol [i.e., vitamin D3], ergocalciferol [i.e., vitamin D2]
or any combination of these two vitamins .... " Bishop i-f 20. Bishop teaches
that 25-0H-D3 (a metabolite of vitamin D2 and D3) deficiency: "can cause
serious bone disorders, including rickets and osteomalacia." Id. at i-f 13.
Specifically, Bishop teaches that:
[O]rally dosing a subject, an animal or a human patient, in need
of Vitamin D supplementation with sufficient cholecalciferol
[i.e., vitamin D3], ergocalciferol [i.e., vitamin D2] or any
combination of these two vitamins to effectively and safely
restore blood 25-[0H D3] levels to optimal levels (defined for
human subjects and patients as equal to or greaterthan 30 ng/mL)
and to maintain blood 25-[0H D3] levels at such optimal
levels ....
Bishop i-f 25. Bishop additionally teaches that:
If the compounds of the present invention are administered in
combination with other therapeutic agents, the proportions of
each of the compounds in the combination being administered
will be dependent on the particular disease state being addressed.
For example, one may choose to administer cholecalciferol
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and/or ergocalciferol with one or more calcium salts (intended as
a calcium supplement or dietary phosphate binder),
bisphosphonates, calcimimetics, nicotinic acid, iron, phosphate
binders, active Vitamin D sterols, 25-hydroxyvitamin D,
inhibitors of CYP24 expression or activity, glycemic and
hypertension control agents, and various antineoplastic agents.
Bishop i-f 59 (emphasis added). It was well known in the art that
Vitamin D deficiency can lead to softening or weakening of bones, e.g.,
osteomalacia and rickets, and that administration of Vitamin D can be
important in maintaining bone health, particularly in sunlight-deprived or
otherwise vitamin D-deficient individuals. See, e.g., Vieth 842. Bishop
teaches that Vitamin D deficiency can be treated by administration of
Vitamin D3 and/or D2. Bishop i-f 59. Bishop also teaches that Vitamin D3
can be co-administered with 25-0H D3, which was well-known in the art to
be a metabolite of vitamin D3 and a pro hormone, i.e., precursor, to the
active form, 1,25 dihydroxyvitamin D3. See Bishop i-f 9. Bishop thus
teaches that co-administration of vitamin D3 and 25-0H D3 can be used in
the maintenance of bone health and the treatment of bone loss diseases (i.e.,
rickets).
Krammer teaches, inter alia: "A method of treatment or prevention of
osteochondrosis in pets which comprises administering to a pet in need of
such treatment or prevention an effective amount of 25-[0H D3] and
vitamin D3" to be used to treat or prevent various bone and joint conditions
in a wide variety of mammalian pets domestic pets. See Krammer, claim 13,
i-fi-1 1-9. Furthermore, Krammer teaches that the combination of 25-0H D3
and vitamin D3 can be administered: "by any conventional means, e.g., as a
veterinary formulation for enteral or parenteral application or, preferably, as
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a feed supplement. When both 25-hydroxycholecalciferol and vitamin D3
are administered such administration may be simultaneous or sequential."
Krammer i-f 11. Krammer also teaches that: "While the ratio of 25-hydroxy-
cholecalciferol: vitamin D3 if administered in combination, is not narrowly
critical, said ratio may range from about 1 :9 to about 9: 1 with a ratio of 1: 1
being preferred," which encompasses Appellants' claimed range of 1 :6 to
6: 1. Id. We find that a person of ordinary skill in the art would understand
that administration "as a veterinary formulation for enteral or parenteral
application" could include weekly or monthly dosage forms.
Simoes-Nunes is directed to: "the use of 25-[0H D3], optionally in
combination with vitamin D3, in the manufacture of a food or veterinary
composition for improvement of bone strength in animals." Simoes-Nunes i-f
1. Although it is true that Simoes-Nunes is directed primarily to food
compositions used in the farming of pigs, Simoes-Nunes also teaches that:
"the invention relates to a method of improving bone strength in animals" in
addition to pigs. Id. Moreover, as the Examiner found, Simoes-Nunes
teaches a dosage ratio of 25-0H D3 to vitamin D3 that closely overlaps
Appellants claimed range of ratios.
Both Krammer and Simoes-Nunes are expressly directed to the
prevention and treatment of, inter alia, osteochondrosis and the promotion
of bone strength. Krammer Abstr., Simoes-Nunes i-f 2. Osteochondrosis was
known in the art to occur not only in fast-growing mammals such as large
dogs and pigs, as taught by Krammer and Simoes-Nunes, but also in
humans, especially children and adolescents. See, e.g., B. Yterhus et al.,
Etiology and Pathogenesis of Osteochondrosis, 44 Vet. Pathol. 429-48
(2007). We find that a person of ordinary skill in the art would understand
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that, because administration of Vitamin D3 and 25-0H D3 promotes bone
strength in pigs and other mammals, and in the prevention of
osteochondrosis, which can also occur in humans, administration of Vitamin
D3 and 25-0H D3 would likely be useful in the promotion and maintenance
of bone health, as recited in claim 1. This is further supported, as explained
in this Decision, by the teachings of Bishop and Veith, which teach that
administration of Vitamin D3 and/or its metabolite, the prohormone 25-0H
D3, are useful in the promotion and maintenance of good bone health in
humans.
The remaining references teach that, more generally, Vitamin D3 and
its metabolites 25-0H D3 and 1, 25-dihydroxyvitamin D3 are effective as
agents in curing or preventing bone diseases. For example, Blunt teaches
that administration of 25-0H D3 is effective in the treatment of rickets in
rats, a common animal model. Blunt 1506. Finally, Veith teaches the
relationship of administered vitamin D3 and serum levels of its metabolite
25-0H D3. See Veith 850-51.
We therefore agree with the Examiner that a person of ordinary skill
in the art, understanding the teachings of the combined prior art references
cited by the Examiner, would understand that a combination of 25-0H D3
and vitamin D3, administered weekly or monthly and within the claimed
range of ratios of25-0H D3 to vitamin D3of1:6 to 6:1, would be useful in
the treatment of such bone-loss conditions as osteoporosis, rickets, and
osteopenia. All of the references are directed to the use of administering
vitamin D and/or its metabolite 25-0H D3 for the treatment of bone-loss
related conditions in mammals, including humans. Bishop teaches
administration of a combination of vitamin D3 and 25-0H D3 to humans for
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the treatment of bone loss-related diseases. Both Krammer and Simoes-
Nunes teach that their claimed compositions, which constitute combinations
of vitamin D3 and 25-0H D3 in the claimed range of ratios, can be
administered as veterinary formulations, which a skilled artisan would
understand could include weekly or monthly dosages. Similarly, Veith is
directed to vitamin D administration as a supplement to prevent bone-loss
conditions, a relationship that is well understood in the art.
Because we find that the combination of references teaches or
suggests all of the limitations of the claims, we affirm the Examiner's
rejection of claims 1-3 and 14--16.
B Claims 10, 11, 19, and 20
Appellants argue these claims together. App. Br. 9. Appellants
advance essentially identical arguments as those related supra with respect
to claims 1-3 and 14--16. Id. at 9-11. Additionally, Appellants argue that
none of the cited references teach or suggest a weekly or monthly dosage as
claimed in the claims. Id. at 12. Appellants assert that, although some of the
references (or a combination of all the references) refer to dosages, they are
continuous dosages, and not weekly or monthly dosages. Id. Appellants
have surprisingly found that a dosage provided just once weekly or once
monthly is sufficient to achieve the desired effect. Id.
We are not persuaded by Appellants' arguments. We have explained
why Appellants' arguments presented supra are not persuasive.
Furthermore, Bishop teaches:
Contemplated minimum oral dosages of either vitamin, or the
combination when used, include at least [ 5 µg] per unit dose, at
least [12.5 µg] per unit dose, at least [37.5 µg] per unit dose, and
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at least [ 50 µg] per unit dose. Contemplated maximum oral
dosages of either vitamin, or the combination when used, include
[ 5 mg] per unit dose, [ 1.25 mg] per unit dose, [250 µg] per unit
dose, and [125 µg] per unit dose. Contemplated oral dosage
ranges of either vitamin, or the combination when used, include
[5 µg] per unit dose to [5 mg] per unit dose, [12.5 µg] per unit
dose to [ 1.25 mg] per unit dose, [37 .5 µg] per unit dose to [250
µg] per unit dose, and [40 µg] per unit dose to [125 µg] per unit
dose.
Bishop i-f 59. 3 Furthermore, Bishop teaches that: "The Vitamin D
preparation to be administered pursuant to the method described herein can
be formulated following techniques known in the art and suitable for
administration via other selected routes." Id. at i-f 39.
Appellants' claims recite weekly dosages of 3 5-1 70 µg and monthly
dosages of 75-500 µg. These are within the range of dosages taught by
Bishop, even if the Bishop doses are administered daily, e.g., 5 µg per unit
dose (once daily) x 7 days= 35 µg. Moreover, we agree with the Examiner
that weekly or monthly administration of vitamin supplements would have
been known to a person of ordinary skill in the art. We therefore affirm the
Examiner's rejection of claims 10, 11, 19, and 20
DECISION
The Examiner's rejection of claims claims 1-3, 10, 11, 14--16, 19, and
20 as unpatentable under 35 U.S.C. § 103(a) is affirmed.
3 Units in brackets have been converted from IU to µg, as per Krammer, to
facilitate comparison with the claims. See Krammer i-f 4.
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No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a)(l ). See 37 C.F.R.
§ 1.136(a)(l )(iv).
AFFIRMED
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