Ex Parte Puder et al

Patent Trial and Appeal Board

May 20, 2016

11267663 (P.T.A.B. May. 20, 2016)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR
11/267,663 11104/2005 MarkPuder
50828 7590 05/24/2016
DAVIDS, RESNICK
NIXON PEABODY LLP
100 SUMMER STREET
BOSTON, MA 02110-2131
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.
701039-054532-C 9627
EXAMINER
BORI, IBRAHIM D
ART UNIT PAPER NUMBER
1629
NOTIFICATION DATE DELIVERY MODE
05/24/2016 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):
bostonpatent@nixonpeabody.com
ipairlink@nixonpeabody.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte MARK PUDER and KATHLEEN M. GURA
Appeal2014-005116
Application 11/267,663
Technology Center 1600
Before ERIC B. GRIMES, RICHARD M. LEBOVITZ, and
JAQUELINE T. HARLOW, Administrative Patent Judges.
LEBOVITZ, Administrative Patent Judge.
DECISION ON APPEAL
This appeal involves claims directed to methods of treatment of liver
disease in human patients who have received parenteral nutrition comprising
administering intravenous fish oil. Appellants appeal from the Examiner's
final rejection of all the pending claims as obvious under 35 U.S.C. § 103.
We have jurisdiction under 35 U.S.C. § 134. The rejections are affirmed-in-
part.
STATEMENT OF CASE
Claims 2-4, 6, 8, 15-17, 21, and 23-28 stand finally rejected by the
Examiner under 35 U.S.C § 103(a) (pre-AIA) as obvious in view of Wei-Jao
Chen and Sung-Ling Yeh, Effects of Fish Oil in Parenteral Nutrition, 19
Appeal2014-005116
Application 11/267,663
NUTRITION 275-279 (2003) ("Chen"); Van Aerde et al., Intravenous Fish
Oil Emulsion Attenuates Total Parenteral Nutrition-Induced Cholestasis in
Newborn Piglets 45(2) PEDIATRRES. 202-208 (Feb. 1999) ("Van Aerde");
Quiros-Tejeira et al., Long-Term Parenteral Nutritional Support and
Intestinal Adaptation in Children with Short Bowel Syndrome: A 25-Year
Experience, 145 J. PEDIATR. 157-163 (Aug. 2004) ("Quiros-Tejeira") and
Yeh et al., Effects of n-3·and n-6 Fatty Acids on Plasma Eicosanoids and
Liver Antioxidant Enzymes in Rats Receiving Total Parenteral Nutrition 13
NUTRITION 32-36 (1997) ("Yeh"). Answer 3.
Appellants provided three declarations in support of the
nonobviousness of the claimed invention. These are:
Declaration of Christopher P. Duggan, M.D. (dated Oct. 23, 2007).
Declaration of Stanley J. Dudrick, M.D. (dated Oct. 22, 2007).
Declaration of Mark Puder, M.D., Ph.D. (dated Nov. 6, 2012).
We find that each of the declarants is qualified to testify on the
matters in their declarations.
Appellants did not argue the claims separately. We select claim 23 as
representative. Claim 23 reads as follows:
23. A method of treatment of parenteral nutrition associated
liver disease (PNALD) in a human infant having short-bowel
syndrome, wherein the human infant is obtaining nutritional
requirements solely through total parenteral nutrition,
comprising administering to said infant having short-bowel
syndrome an intravenous lipid emulsion consisting of fish oil-
derived omega-3 fatty acids, wherein the infant having short-
bowel syndrome is not administered phytosterols or plant
derived fatty acids during said treatment of PNALD.
Appeal Br. 29 (Claims Appendix).
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OBVIOUSNESS REJECTION
The Specification teaches that nutritional support through parenteral
nutrition (PN) "is necessary when patients can not be fed orally, for example
when a patient has an impaired GI tract and is unable to tolerate enteral
feedings." Spec. ,-r 1. The Specification teaches that PN is a solution which
contains various nutritional ingredients. Id. at ,-r 2. "PN is administered
concurrently with an intravenous lipid emulsion that provides essential fatty
acids." Id. The Specification lists various commercially available lipid
emulsions which are said to be composed of vegetable oil whose fatty acid
content consists primarily of the essential omega-6 fatty acids. Id.
According to the Specification, the "use of PN in patients of all ages
has been associated with liver disease, ranging from hepatic steatosis to
cirrhosis and ultimately liver failure." Id. at ,-r 3. Dr. Dudrick, a physician
who "pioneered the development of total parenteral nutrition (TPN) through
intravenous hyperalimentation," explained that long-term PNALD
(parenteral nutrition associated liver disease) is one of the main causes of
death in adults and children. Dudrick Deel. ,-r,-r 3 and 7. Parenteral nutrition
is nutrition that is taken in through routes other than the digestive or
alimentary canal, e.g., intravenously. 1
The Specification teaches:
The present invention is based on the discovery that parenteral
nutrition (PN) induced liver disease, e.g. fatty liver disease, can
be prevented and even reversed by administration of primarily
omega-3-fatty acid with PN rather than the administration of
the standard intravenous lipid emulsions that contain primarily
plant derived omega-6 fatty acid.
1 http ://medical-dictionary. thefreedictionary. com/parenteral
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Spec. il 7.
There are four independent claims at issue in this appeal; claims 21,
23, 25, and 28. Each of the claims has a step of administering,
intravenously, a lipid emulsion which consists of fish oil-derived omega-3
fatty acids. The specific wording varies from claim to claim. Claims 21, 23,
and 25 exclude administration of plant-derived omega-6 fatty acids or plant
fatty acids. However, claim 28 does not exclude plant fatty acids and we
treat this claim differently from claims 21, 23, and 25.
Each of the claims is also directed to methods for treating liver
disease. Claims 23 and 25 are for treating parenteral-associated liver disease
(PNALD) in a human infant that has short-bowel disease. Claim 21 is for
treating liver disease in a human patient, where the patient is under the age
of 12. Claim 28 is the broadest claim; it is open to the administration of
plant-derived fatty acids and it is not restricted to the patient classes of
claims 21, 23, and 25, but is for "treating a human patient having liver
disease."
The Examiner rejected the claims over Chen, Van Aerde, Quiros-
Tejeira, and Yeh.
Quiros-Tejeira is a retrospective study of children with short-bowel
syndrome who required PN for more than three months. Quiros-Tejeira 157.
Quiros-Tejeira reports that PN-related morbidity and mortality have been
major concerns since the initiation of its use, and describes liver disease and
cholestasis as problems associated with long-term PN. Id. at 157-158 and
162. Quiros-Tejeira teaches that fat emulsions are administered to patients
with short bowel-syndrome. Id. at 158.
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The Chen, Van Aerde, and Yeh publications describe animal studies
to determine the effects of parenterally administered fish oil. The following
findings of fact from the animal studies are summarized below:
Chen
FF 1. Chen is a review article describing the effects of fish oil in
parenteral nutrition.
FF2. Chen lists several benefits of fish oil, including "amelioration of
the severity of diet-induced hepatic steatosis [fatty liver]" and "less
accumulation of lipid peroxidation products in liver tissue." Chen 27 5
("Results").
FF3. Chen identifies hepatic dysfunction as "a well-described
complication of TPN [total parenteral nutrition], and hepatic steatosis is the
earliest and most frequently reported histological change." Id. at 276, col. 2.
FF4. Chen compared fish oil to several vegetable oils and concluded
that "only TPN with a fat emulsion prepared with fish oil does not cause
hyperlipidemia or induce hepatic steatosis in normal rats." Id.
FF5. Chen also reported that "a study investigating the effects of TPN
containing fish oil emulsion on diet-induced hepatic steatosis in rats was
performed. Those results showed that fish oil infusion can ameliorate the
severity of hepatic steatosis induced by a high-fat diet." Id. (footnotes
omitted).
Van Aerde
FF6. Van Aerde teaches that "TPN-associated liver abnormalities are
common in adults and children receiving long-term TPN. The development
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of TPN associated liver disease is particularly relevant in the premature
newborn who is at significant risk of developing chronic liver disease." Van
Aerde 1 (footnotes omitted).
FF7. Van Aerde describes a model of TPN cholestasis in the newborn
pig. Id. at 2.
FF8. Van Aerde describes treating three groups of newborn pigs. Id.
at 2. One group was fed sow's milk. Id. The second group was fed via
TPN with a composition comprising soybean oil triglycerides. The third
group was fed via TPN with a composition comprising an emulsion of fish
oil triglycerides. Id.
FF9. Van Aerde reported "Newborn piglets fed TPN with i.v. FO
[fish oil] as the lipid source did not develop cholestasis compared with
animals fed the soy bean oil emulsion, which is similar to the clinically used
products." Id. at 9.
FFlO.
In summary, an i.v. lipid emulsion high in eicosapentaenoic and
docosahexaenoic acid reduces impairment of bile flow as seen in
cholestasis caused by conventional TPN .... Further development and
testing of PO-enriched emulsions are needed to determine the clinical
application in parenteral nutrition for human neonates.
Id. at 10.
Yeh
FF 11. Yeh describes a study of TPN in rats. Yeh describes
maintaining the rats on TPN for seven days. Yeh, Abstract. "One
experimental group received a safflower oil emulsion, whereas the other
group received a fish oil emulsion." Id.
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Application 11/267,663
FF 12. Based on its experimental results, Yeh states that it "is
suggested that fish oil may be of benefit to TPN patients in preventing
platelet aggregation." Id. at 35.
Rejection
The Examiner found that the animal models described by Chen and
Van Aerde would have motivated one of ordinary skill in the art to have
administered TPN solely with fish oil since each publication describes the
benefit of fish oil in ameliorating TPN-associated liver abnormalities. Final
Rej. 8-9 and 10. The Examiner found animal models are applicable to
humans because they are often in agreement with human studies. As an
example, the Examiner cited Yeh's results "comparing TPN administration
of fish oil lipid emulsion with safflower oil lipid emulsion to rats [which]
were in agreement with finding in human studies (see page 3 5, i-f on the
left)." Id. at 12. The Examiner also found that Quiros-Tejeira teaches that
treatment of children with short bowel syndrome with total parenteral
nutrition is well known, including with fat emulsions, providing further
reason to apply Chen and Van Aerde's teaching to children with short bowel
syndrome as recited in claims 23 and 25. Id. at 8 and 9.
Appellants contend that "the scope of the prior art was skeptical of the
use of fish oil-derived omega-3 fatty acids because it was widely known to
have serious side effects when administered in significant doses, and was
explicitly contraindicated for the uses encompassed by the present claims."
Appeal Br. 18. Appellants also contend that the claimed invention addresses
a long felt unmet need to treat PNALD. Id. at 22. We consider these
arguments below.
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Skepticism of the use offish oil derived omega-3 fatty acids
Appellants contend that the declarations establish that "it was well-
known at the time the invention was made that even dietary supplementation
with fish oil taken as an enteral formulation caused significant side effects,
including increased risk of bleeding, severe diarrhea, and increased LDL
levels." Appeal Br. 20-21. As evidence of this, Appellants point to
paragraphs 9, 10, 14-16, and 18 of Dr. Puder' s declaration and the package
insert to Omegaven. Id.
The preponderance of the evidence does not support Appellants'
contention about the unobviousness of utilizing a fish oil in humans as
parenteral nutrition.
In reaching his opinion, Dr. Puder relies on the package insert of
Omegaven. Puder Deel. i-f 9. Omegaven is a fish oil based emulsion with a
high percentage of omega-3 fatty acids, eicosapentaenoic acid (EPA) and
docosapentaenoic acid (DHA). Spec. i-f 4. Dr. Puder stated that the package
insert teaches that there are side effects of fish oil "even when taken in small
doses as an enteral supplement." Puder Deel. i-f 9. Dr. Puder stated that it is
"known that the side effects are related to the dosages used, and that high
doses have harmful effects, such as increased risk of bleeding, severe
diarrhea, and increased LDL levels (see, e.g., the 'undersirable [sic] effects'
section of the OMEGA VENâ„¢ product insert submitted concurrently ... )."
Id.
We do not find Dr. Puder' s testimony persuasive.
The Specification discloses that Omegaven is a fish oil emulsion that
"has been developed and used in the European market." Spec. i-f 4.
Consequently, we consider Omegaven to be prior art to the claimed subject
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matter. Although we have not been directed to evidence of the publication
date of the Omegaven package insert, we have taken it to be prior art.
Dr. Puder points to various warnings in the package insert concerning
side effects and patient populations to which Omegaven should not be
administered. Nonetheless, the insert establishes that Omegaven was
administered to humans for five explicitly named indications ("Beneficial
for"). Like any drug, Omegaven has side-effects and contraindications, but
the benefits outweigh the potential harm.
Dr. Puder's testimony about the significant side-effects of Omegaven
that would have deterred the skilled worker from administering it to treat
short bowel syndrome and patients with liver disease is not credible. For
example, Dr. Puder mentions "increased risk of bleeding" as one significant
side-effect. However, the package insert states:
The infusion of Omegaven can cause a prolonged bleeding time
and an inhibited platelet aggregation. Therefore, Omegaven
should be administered \'l1ith caution to patients requiring
anticoagulant therapy even with regard to a possible reduction
of anticoagulants.
Omegaven 2 (pages are not numbered; this appears on the second
consecutive page). Thus, the insert identifies bleeding as an undesirable
effect, but mentions it with respect to a specific population of patients and
provides instructions on how to use it with this patient population.
Dr. Puder also testified that "it was widely believed at the time of the
invention that administration of large amounts of fish oil was dangerous due
to the lack of essential fatty acids in fish oil, which increased the risk of the
patient developing essential fatty acid deficiency (EFAD)." Puder Deel.
i-f 15. To support his statement, Dr. Puder cited an article published in the
Journal of Parenteral and Enteral Nutrition, 28(6): S39-S70 (2004) titled
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"Safe Practices for Parenteral Nutrition" ("Safe Practices"). However, in
paragraph 15, what Dr. Puder cites in the article as support is a statement
that deficiency of essential fatty acids can occur "after fat-free PN." Safe
Practices S55. Dr. Puder's testimony is therefore not factually supported.
As pointed out by Drs. Puder and Duggan, the Omegaven package
insert, on the first page, discloses it should not be given to liver patients and
infants and newborns:
Omegaven should not be administered in patients with severe
liver or renal insufficiency. Omegaven should not be used in
premature infants, newborns, infants and children due to limited
experience.
However, both Chen and Van Aerde provide reasons to have utilized
Omegaven in these populations because of beneficial effects on liver defects
associated with PN. FF2, FF4, FF5, FF9, FFlO. Dr. Puder attempts to
distinguish Chen and Van Aerde because they are animal models. Puder
Deel. i-fi-f 14, 16, 17. Dr. Duggan also expresses the same reservations about
the animal models. Duggan i-f 11. Nonetheless, medical research typically
begins in an animal model as a prelude to treatment in a human. Each of
Chen, Van Aerde, and Yeh describes positive results using fish oil in
animals, and show no reservation about whether they would be toxic in
human populations, including in neonates. FF 10. Thus, the statements by
the declarants about why one of ordinary skill would not use fish oil because
of toxicity, contraindications, etc. are outweighed by the teachings in Chen,
Van Aerde, and Yeh. We conclude that one of ordinary skill in the art
would have had reason to administer fish oil to the patient classes recited in
claims 21, 23, 25, and 28.
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Fish oil administered and plant fatty acids excluded
Independent claims 21, 23, and 25 administer fish oil omega-3 fatty
acids but do not administer plant-derived fatty acids. The patient
populations are those who obtain nutritional requirements solely through
parenteral nutrition. While we agree with the Examiner that a
preponderance of the evidence supports providing fish oil to this patient
population based on the experiments described in Chen, Van Aerde, and
Yeh, as well as other evidence in this proceeding (see below), Appellants
have provided persuasive evidence that one of ordinary skill in the art would
not have solely administered fish oil as the only oil emulsion. Appellants
also provided adequate evidence that their invention satisfied a long-felt
unmet need.
According to Dr. Dudrick, the "current FDA approved lipid emulsion
for PN is soy-based oil emulsion such as Intralipid and Liposyn II or soy-
based and olive oil mixtures such as Clinoleic." Dudrick Deel. ,-r 8. Dr.
Dudrick explains that soy was used with fish oil because soy contains
linoleic acid which was believed to be an essential fatty acid. Id. at ,-r 12 (p.
6).
Id.
Fish oil fatty emulsions used in parenteral nutrition, prior to the
present invention, have always been used with supplemental
omega-6-fatty acid, e.g., soy, which contains linoleic acid
believed to those skilled in the art to be an essential fatty acid.
In fact, one skilled in the art would not use fish oil emulsions
alone (i.e. not mixed with a soy oil containing lipid emulsion)
because it was believed that in patients dependent on TPN a
failure to administer a fat emulsion containing omega-6-fatty
acids in the form of soy would result in the patient developing
an essential fatty acid deficiency (EF A).
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"Safe Practices" supports Dr. Dudrick's testimony. "Safe Practices"
teaches that "Failure to provide at least 2% to 4% of the total caloric intake
as linoleic acid ... may lead to a deficiency of [this] ... essential fatty
acid[]. "Safe Practices," S53, col. 1, i-f 4. Dr. Dudrick further describes the
negative consequences of essential fatty acid deficiency and why the skilled
worker would not consider the use of fish oil alone because of this risk.
Dudrick Deel. i-f 12 (pp. 6-7).
In addition to this, Dr. Dudrick attached an article entitled "A Dr's
Push for Drug Pits Him against Its Maker," originally printed November 13,
2006 in The Wall Street Journal ("WSJ"). The article describes the
inventors' efforts to get Omegaven approved for use in the United States to
treat children with small bowel syndrome. According to the article, the
maker of Omegaven is against it. John R. Ducker, the president of research,
development, and strategic marketing division of Fresenius Kabi, the
manufacturer of Omegaven, is stated as saying:
Omegaven isn't what "we see as the best product for this kind
of application[.]" ... He says Omegaven, developed 15 years
ago, was intended as a supplement, and not to be given alone.
The company says it doesn't contain all the essential fatty acids
babies need.
WSJ 1.
The article also quotes Dr. Christopher P. Duggan, director of clinical
nutrition at Children's Hospital, who examined one of the pediatric patients
who had been treated with Omegaven. Id. at 5. The article states that the
child may "still have some liver damage, but there were no signs of the
severe, life-threatening problems that existed before." Id.
[Dr. Duggan] says he understands how parents might feel that
Omegaven had saved their child's life. But he cautions that
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Id.
many treatments were given to the babies because they were so
sick, making it hard to determine if it was Omegaven or
something else that made the difference in their recovery.
"I am a total therapeutic skeptic," Dr. Duggan says. Even with
the promising results so far, to really know that Omegaven is
working, he says, "I want to see the results of a trial."
Dr. Duggan, in his declaration filed during this examination,
acknowledged his initial skepticism, but stated that after reviewing the
results of the first 18 of the 56 patients treated with Omegaven, he is
"convinced that, in conjunction with standard medical, nutritional, and
surgical care, the substitution of a fish oil based emulsion that contains
omega-3-fatty acids that are not plant-derived and does not contain plant-
derived omega-6-fatty acids is effective in treating TPN-associated liver
disease." Duggan Deel. i-f 11.
Appellants also a provided post-filing date publication by I. R.
Diamond et al. ("Changing the Paradigm: Omegaven for the Treatment of
Liver Failure in Pediatric Short Bowel Syndrome," Journal of Pediatric
Gastroenterology and Nutrition, 48: 209-215, 2009). Diamond describes
treatment of patients with Omegaven. Diamond acknowledges the
inventors' approach of administering only Omegaven, but they chose to
administer it with Intralipid, a soy oil preparation, because "we believe that
such a balanced lipid mix makes more sense physiologically than a lipid that
is composed entirely of either predominantly [omega]6FA or [ omega]3FA."
Diamond 214 (col. 1, second full paragraph). Yet, Diamond states that,
despite their views on the benefits of both [omega]6FA and [omega]3FA,
they maintained a flexible approach, and in 6 cases which started out with
both Intralipid and Omegaven, Intralipid was discontinued "on the basis of
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the clinical judgment of our multidisciplinary team that treatment response
was either inadequate or that there was significant disease progression." Id.
at 214 (cols. 1-2). Two other cases were also reverted to Omegaven only
and showed resolution ofhyperbilirubinemia. Id. at col. 2. Thus, even those
skeptical of administering fish oil alone, did so when the fish oil and soy oil
emulsion did not work.
In sum, a preponderance of the evidence shows the skilled worker,
even after the filing dates, had doubts about using Omegaven only for
treatment of parenteral nutrition associated liver disease. This skepticism is
further evidence of the nonobviousness of claims 21, 23, and 25.
Long-felt but unsolved need
Long-felt unsolved need is one of the relevant secondary
considerations when determining the obviousness of a claimed invention.
Leo Pharm. Prods., Ltd. v. Rea, 726 F.3d 1346, 1359 (Fed. Cir. 2013).
Secondary considerations are "not just a cumulative or confirmatory part of
the obviousness calculus but constitute [] independent evidence of
nonobviousness ... [and] enable [] the court to avert the trap of hindsight."
Leo, 726 F.3d at 1358 (internal quotation marks and citations omitted).
"This objective evidence must be 'considered as part of all the evidence, not
just when the decisionmaker remains in doubt after reviewing the art."'
Transocean Offshore Deepwater Drilling, Inc. v. Maersk Drilling USA, Inc.,
699 F.3d 1340, 1349 (Fed. Cir. 2012) (internal citations omitted).
"[L Jong-felt need is analyzed as of the date of an articulated identified
problem and evidence of efforts to solve that problem." Texas Instruments
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Inc. v. International Trade Commission, 988 F.2d 1165, 1178 (Fed. Cir.
1993).
There is considerable evidence before us that liver disease and
abnormalities had been long recognized as a problem associated with long
term total parenteral nutrition. Van Aerde cited scientific articles published
in 1995, 1981, and 1979 for this problem in adults, children and newborns,
respectively. Van Aerde i-fi-f l, 10, 11. Quiros-Tejeira cited a 1984 article
(fn. 5) that "PN-related morbidity and mortality [in short-bowel syndrome
acquired in infancy] have been major concerns since the initiation of its
use." Quiros-Tejeira 157 and 162. The study by Quiros-Tejeira was of
children who required PN support from 197 5 to 2000 to learn about the
clinical outcome of children with small bowel syndrome and how to increase
survival. Id. at 157, 161-162. Dr. Duggan also testified on the extent of the
problem, as did Dr. Dudrick. Duggan Deel. i13; Dudrick Deel. i-fi-17 and 8.
The Examiner's statement that "there is no showing that others of ordinary
skill in the art were working on the problem and if so, for how long"
(Answer 7) ignores an extensive record documenting TPN-associated liver
disease over decades and attempts to solve it.
There is also considerable credible evidence that the claimed subject
matter met the "unsolved" need to treat TPN-associated liver disease. Dr.
Dudrick testified in his declaration that the "underlying cause(s) of PNALD
remains largely unknown and controversial." Dudrick Deel. i18. Dr.
Dudrick stated that scientists, including himself, "have been struggling for
decades to find a treatment for PNALD, which is associated with a relatively
high mortality rate in patients receiving long-term parenteral nutrition
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(TPN)." Id. Dr. Dudrick described attempts to solve it, identifying
publications to support his opinion. Id.
Dr. Dudrick testified that the inventors discovered a solution to the
problem:
Drs. Puder and Gura have now discovered a solution for this
long felt but unresolved problem of liver disease experienced in
patients receiving long-term TPN. They have discovered that
parenteral nutrition-associated liver disease (PNALD) can be
prevented and even reversed in patients receiving parenteral
nutrition by the administration of a fat emulsion containing
omega-3 fatty acids and lacking phytosterols and plant derived
omega-6 fatty acids, e.g. fish oil.
Id. at i19.
Dr. Dudrick characterized their results as "unexpected, dramatic and
revolutionary." Id.
Dr. Duggan, who is Director of Clinical Nutrition and the Medical
Director of the Short Bowel Syndrome Program at the Children's Hospital
Boston, Massachusetts, also testified that the claimed invention "provides a
solution to the long felt but unresolved problem of TPN-associated liver
disease experienced by thousands of children and adults worldwide since the
introduction of TPN as the standard of care." Duggan Deel. i1 6. Dr.
Duggan stated that from the human study, "one can see that the mortality
rate due PNALD is greatly reduced from 33% for TPN with soy oil based
emulsion to 0% for TPN with fish oil based emulsion, and the need for a
liver transplant due to TPN-associated liver disease is completely eliminated
for the 49 weeks that the children were followed." Id. at i-f 11.
The Examiner did not consider the evidence persuasive because Chen
and Van Aerde describe the benefit of fish oil in liver disease associated
with TPN. Answer 6-7. However, Appellants have persuasively argued
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that the skilled worker would not have administered fish oil alone because of
the problem of essential fatty acid deficiency, but would have included a
plant based oil, such as a soy-derived oil. Claims 21, 23, and 25, however,
exclude plant fatty acids and plant omega-6 fatty acids. The cited
publications do not suggest fish oil, alone.
Summary
For the foregoing reasons, we reverse the rejection of independent
claims 21, 23, and 25, and dependent claims 2-4, 8, 15-17, and 27.
Claim 28
Claim 28 is directed to a method of treating liver disease comprising
administering "a lipid emulsion, wherein the lipid emulsion consists of fish
oils rich in omega-3 fatty acids." The claim does not exclude administering
plant fatty acids. The claim thus covers fish alone, or fish oil and plant
derived fatty acids. Consequently, unlike claims 21, 23, and 25, we find that
the combination of Chen, Van Aerde, Yeh, and Quiros-Tejeira in the context
of extensive prior art cited in this examination suggests the subject matter of
claim 28. For example, we cannot ignore Dr. Dudrick's statement that fish
oils used in parenteral nutrition "have always been used with supplemental
omega-6-fatty acid, e.g., soy." Dudrick Deel. i-f 12 (p. 6).
Accordingly, we affirm the rejection of claim 28, and dependent
claims 6, 24, and 26.
TIME PERIOD
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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)(iv).
AFFIRMED-IN-PART
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