Ex Parte CALTON

Patent Trials and Appeals Board

May 10, 2019

14692151 - (D) (P.T.A.B. May. 10, 2019)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
14/692,151 04/21/2015
7055 7590 05/14/2019
GREENBLUM & BERNSTEIN, P.L.C.
1950 ROLAND CLARKE PLACE
RESTON, VA 20191
FIRST NAMED INVENTOR
Gary J. CALTON
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.
P47512 3352
EXAMINER
GEMBEH, SHIRLEY V
ART UNIT PAPER NUMBER
1615
NOTIFICATION DATE DELIVERY MODE
05/14/2019 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):
gbpatent@gbpatent.com
greenblum.bernsteinplc@gmail.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte GARY J. CALTON1
Appeal2018-005002
Application 14/692, 151
Technology Center 1600
Before RICHARD M. LEBOVITZ, ULRIKE W. JENKS, and
ROBERT A. POLLOCK, Administrative Patent Judges.
LEBOVITZ, Administrative Patent Judge.
DECISION ON APPEAL
This appeal involves claims directed to methods of ameliorating post-
dialysis washout comprising administering amino acid. The Examiner
rejected the claims under 35 U.S.C. § 103. Pursuant to 35 U.S.C. § 134,
Appellant appeals the Examiner's determination that the claims are
unpatentable. We have jurisdiction for the appeal under 35 U.S.C. § 6(b).
The Examiner's decision is affirmed.
1 The Appeal Brief ("Appeal Br." filed Nov. 29, 2017) lists Calwood
Nutritionals, LLC as the real-party-in-interest. Appeal Br. 3.
Appeal2018-005002
Application 14/692, 151
STATEMENT OF THE CASE
The claims stand rejected by the Examiner as follow:
1. Claims 1-5, 7-10, and 11-15 under 35 U.S.C. § 103 as obvious in
view of M. Sundell et al., "Oral Protein Supplementation Alone Improves
Anabolism in a Dose-Dependent Manner in Chronic Hemodialysis Patients,"
J. Ren. Nutr., 2009, 19(5): 412-421 (pages numbered 1-16 in copy cited by
Examiner) ("Sundell"), J. Navarro et al., "Amino acid losses during
hemodialysis with polyacrylonitrile membranes: effect of intradialytic amino
acid supplementation on plasma amino acid concentrations and nutritional
variables in nondiabetic patients," Am. J. Clin. Nutr., 2000, 71 :765-773
("Navarro"), and L. Pupim et al., "Intradialytic Oral Nutrition Improves
Protein Homeostasis Chronic Hemodialysis Patients with Deranged
Nutritional Status," J. Am. Soc. Nephrol., 2006, 17(11):3149-3157
("Pupim"). Ans. 4.
2. Claims 11-20 under 35 U.S.C. § 103 as obvious in view of
Sundell, Navarro, Pupim, and Wolfe et al. (U.S. Pat. No. 7,790,688 B2,
issued Sept. 7, 2010) ("Wolfe"). Ans. 7.
Claim 1, which is representative of the appealed subject matter, is
reproduced below:
1. A method of ameliorating post-dialysis washout in a
patient subjected to hemodialysis or peritoneal dialysis
comprising orally administering an effective amount of at least
one free amino acid and/or a hydroxy or keto analog thereof to
said patient within a period of: from 45 minutes prior to the end
of a dialysis session to 2 hours subsequent to the end of a
dialysis session.
2
Appeal2018-005002
Application 14/692, 151
OBVIOUSNESS BASED ON SUNDELL, NAVARRO, AND PUPIM
The Examiner found that Sundell describes orally administering free
amino acids (phenylalanine, histidine, and tryptophan) to a hemodialysis
patient as required by claim 1. Ans. 4. The Examiner found that Sundell
administered the amino acids 30 minutes before and 30 minutes after the
start of dialysis, but not "from 45 minutes prior to the end of a dialysis
session to 2 hours subsequent to the end of a dialysis session," as required by
claim 1. Ans. 4. To meet this deficiency, the Examiner cited disclosure in
Navarro that amino acids have been administered near the end of or
immediately after hemodialysis and that it is known that amino acids are lost
during the four-hour hemodialysis period. Id. Based on these disclosures
from Navarro, the Examiner found it would have been obvious to have
administered amino acids during the claimed period of time. Ans. 4-5.
The Examiner also cited Pupim for administering amino acids in three
separate dosages over a four hour dialysis period: 1) at the start of dialysis,
2) 1.5 hours (90 minutes) after the start, and 3) 2.5 hours (150 minutes) after
the start. Ans. 5. This additional teaching, the Examiner found, would also
have given one of ordinary skill in the art reason to have arrived at the
claimed time period for amino acid administration. Id.
The Examiner determined it would have been obvious to have
selected a time point to administer amino acids within the claimed interval to
"improve[] whole body and skeletal muscle protein anabolism in a dose
dependent manner in chronic HD [hemodialysis] patients" as described in
Sundell. Ans. 6.
Appellant contends that the Examiner erred. Appellant disparages
Navarro's teaching of "prior studies" in which "AAs [ amino acids] were
3
Appeal2018-005002
Application 14/692, 151
administered near the end of or immediately after the hemodialysis session
(30, 31) and in all cases were infused in a glucose solution (22, 30, 31)."
Navarro 766. Appellant argues that Navarro "only mentions these other
studies to contrast them from its study of the effects of intradialytic amino
acid administration (i.e., administration of amino acids during dialysis)
without glucose on plasma amino acid levels and amino acid losses in the
dialysate." Appeal Br. 16. Appellant argues that Navarro "does not discuss
the results of those studies, nor any effect or benefit attributable to
administering amino acids near the end of or immediately after a
hemodialysis session." Id. Thus, Appellant contend that "Navarro et al.' s
mention of those other studies would not have given one of ordinary skill in
the art motivation or reason to modify Sundell et al. in the manner alleged by
the Examiner." Id.
These arguments do not persuade us that the Examiner erred in
rejecting the claims as obvious. Two of the publications cited by the
Examiner describe oral administration of amino acids to patients undergoing
hemodialysis. Sundell teaches administering the amino acids 30 minutes
before hemodialysis and 30 minutes after or 210 minutes before the end of
dialysis of the 4 hour (240 minutes) dialysis period. Pupim describes three
doses during hemodialysis, with the last dosage at 2.5 hours (150 minutes)
after the start of hemodialysis or 90 minutes before the end of the 4 hour
(240 minutes) dialysis period. Pupim 3150 (2nd column). (Compare claim 1
which administers amino acids from 45 minutes before the end of dialysis.)
As explained below, each of these publications administer oral amino acids
during hemodialysis to treat protein catabolism associated with
hemodialysis.
4
Appeal2018-005002
Application 14/692, 151
Sundell teaches that hemodialysis is a "protein catabolic event" and
that "administration of nonselective nutritional supplementation containing
all macronutrients ( amino acid, lipid, and carbohydrate) during HD
counteracts this adverse effect." Sundell 5 ("Discussion"). Sundell's studies
"sought to examine the efficacy of an oral supplementation containing
amino acids alone" during dialysis. Id.
Pupim discloses that hemodialysis is associated with protein loss
which is a catabolic process. Pupim 3149. Pupim discloses that oral
nutritional supplementation with amino acids during hemodialysis (Pupim
3150 (2nd column)) can reverse the HD-associated protein catabolism
(Pupim 3154-3155). Pupim teaches that oral administration of amino acids
is more desirable than parenteral (intravenous) administration of them
because it is more affordable (Pupim 3149, 3156) and its affects last longer
(Pupim 3562). In contrast, Pupim teaches that "the anabolic [protein
building; increased concentration of amino acids in patient blood plasma]
effects of IDPN seem to be limited to the period of administration, with no
evidence of persistent anabolism once its infusion is shut off." Pupim 3149.
2 "Furthermore, the beneficial effects of oral supplementation extended to the
post-HD [hemodialysis] period in the muscle compartment, providing an
additional positive effect above and beyond of what is observed with IDPN
[intradialytic parenteral nutrition]. Taken together, these results strongly
indicate that PO nutritional supplementation is an excellent strategy to
prevent and potentially treat deranged nutritional status. When the financial
advantages of oral supplementation over IDPN are included in the final
analysis, it is reasonable to suggest that PO supplementation would be the
treatment of choice for all CHD [ chronic hemodialysis] patients that require
nutritional intervention." Pupim 3156 ( emphasis added].
5
Appeal2018-005002
Application 14/692, 151
Appellant states that Sundell distinguishes its studies from Pupim.
Appeal Br. 23. For this reason, Appellant argues "one of ordinary skill in
the art clearly would not have been motivated to modify Sundell et al. in
view of Pupim et al." Id. While Sundell refers to Pupim's studies, it does
not disparage it as Appellant's argues. Appeal Br. 23. Sundell teaches that
"[ s Jeveral studies showed that parenteral and oral nutritional
supplementation administered during hemodialysis led to a protein anabolic
response in CHD patients" and referenced footnotes 3-5, where footnote 4 is
Pupim. Sundell 2. Sundell further comments on Pupim:
Further evidence in line with the dose-response relationship in
nutritional supplementation comes from previous data from our
laboratory showing an even stronger anabolic response, both in
skeletal muscle and whole-body net protein anabolism, when
higher amounts of amino acids were supplemented. 4
Sundell 6 (2nd full paragraph).
We read nothing in either of these disclosures from Sundell referenced
by Appellant which would have dissuaded one of ordinary skill in the art
from considering both Sundell and Pupim in determining whether the
claimed time period would have been obvious at the time of the invention.
The key issue is whether one of ordinary skill in the art would have
had reason to administer an amino acid supplement orally 45 minutes from
the end of dialysis until 2 hours afterwards in view of the teaching of
Sundell of administering amino acids 210 minutes and Pupim of 90 minutes
before the end of dialysis.
In view of the "normal desire of scientists or artisans to improve upon
what is already generally known" (In re Peterson, 315 F.3d 1325, 1329-30
(Fed. Cir. 2003)), the skilled worker would have had reason to vary the time
intervals in which the oral amino acids were administered to improve the
6
Appeal2018-005002
Application 14/692, 151
anabolic effects on protein metabolism and extend them to the post-HD
period as described by Pupim (fn.2).
Navarro provides further reason to optimize the oral administration
times disclosed in Sundell and Pupim. Navarro teaches that "In prior
studies, AAs were administered near the end of or immediately after the
hemodialysis session (30, 31) and in all cases were infused in a glucose
solution (22, 30, 31 )" (Navarro 766 (1st column), providing a reason to
administer the amino acids at the end of the hemodialysis period, consistent
with the third oral dosage given by Pupin at 90 minutes before the end of
dialysis.
Appellant attempts to distinguish Navarro's statement about the prior
art because it was intravenous administration, provided along with glucose,
and does not discuss the benefit of the results in the "prior studies."
It was known at the time of the invention that amino acids were lost
during hemodialysis. Navarro specifically teaches:
The pathogenesis of malnutrition in dialysis is multifactorial
(12-14). In addition to low nutrient intake, hormonal and
metabolic derangements, and superimposed illness, dialysis-
related factors [ specifically, loss of nutrients, including amino
acids (AAs)] may have a substantial effect on malnutrition (15,
16). It was estimated that AA losses during the dialysis
procedure represent between 3% and 12% of the patient's daily
protein intake (17-19).
Navarro 765 (2nd column) (brackets in original).
It is well established by Navarro, Sundell, and Pupim, that amino acid
supplementation at least during hemodialysis was advantageous to
counteract protein catabolism during hemodialysis. Thus, Navarro's failure
to discuss the results obtained in the referenced "prior studies" does not
lesson the teaching that the skilled worker had administered amino acids at
7
Appeal2018-005002
Application 14/692, 151
the end of the hemodialysis period to treat the loss of amino acids that
occurred during dialysis. Consistent with Navarro's statement that amino
acids were "administered near the end" of hemodialysis, Pupim administered
acids 90 minutes near the end in the last hour of hemodialysis (2.5 hours
after HD initiated in a 4-hour dialysis). Pupim 3150 (2nd column). Thus, the
evidence as a whole supports the Examiner's finding that it would obvious
to one of ordinary skill in the art to have determined an optimal time to
orally administer amino acids at the end of dialysis.
Appellant also contrasts Navarro's method in which amino acids are
administered continuously and intravenously for the four hour dialysis
period, while Sundell administers amino acids orally and at two discrete
intervals, 30 minutes before and after the start of hemodialysis. Appeal Br.
19. Appellant provides evidence that "different routes of drug
administration can result in different onset rates and durations of drug
action," stating there is delay in drug availability in oral administration in
contrast to intravenous administration. Id. Appellant concludes that "due at
least to the differences in the onset rates and duration of drug action between
oral and intravenous administration routes, one of skill in the art would not
have looked at intravenous dosing protocols to determine or modify oral
dosing protocols, and vice-versa, to achieve the same effect." Id. at 20.
We agree with Appellant that there are differences between oral and
intravenous administration. However, both approaches were known to be
successful as established by Navarro, Sundell, and Pupim. Navarro does not
distinguish between oral and intravenous administration in its reference to
previous studies: "Several studies showed that parenteral [intravenous] and
oral nutritional supplementation administered during hemodialysis led to a
8
Appeal2018-005002
Application 14/692, 151
protein anabolic response in CHD patients." Sundell 2 (emphasis added).
Pupim expressly teaches that oral administration was advantageous as
compared to parenteral administration because the anabolic affects
persevered after the hemodialysis period (fn.2), providing reason to
determine optimal administration times at the end of dialysis to further the
anabolic effects. The Examiner did not rely on intravenous administration to
reach the limitation of "from 45 minutes prior to the end of a dialysis session
to 2 hours subsequent to the end of a dialysis session" because both Sundell
and Pupim describe oral administration.
Appellant contends that the claimed invention achieves a different
result than achieved in the cited prior art. Appellant argues that the effect
reported by Sundell and Navarro "was increased concentrations of amino
acid in the plasma during dialysis compared to control." Appeal Br. 21.
Appellant contends his own Specification "describes a different desired
effect-timing the oral administration so that the amino acids are leaving the
stomach near the end of dialysis so that they are available in the circulating
blood after dialysis is completed." Id. Appellant, citing paragraph 30 of the
Specification, states that "correct timing of orally taking the amino acids is
very important, because if done too early, the amino acids make it to the
circulating blood before dialysis is completed and are lost due to the
dialysis." Id. However, Appellant explains that "if timed correctly, the
amino acids are available after dialysis to increase circulating levels of
amino acids in the blood stream, removing the body's need to break down
muscle to obtain the correct level of circulating amino acids in the blood
stream." Id. Appellant further states, that as disclosed in paragraph 31 of
the Specification, "the present inventor discovered that during a period of
9
Appeal2018-005002
Application 14/692, 151
from approximately 45 minutes prior to the end of hemodialysis to 2 hours
after the end of hemodialysis, the drinking of a solution or eating a matrix of
amino acids ameliorates post-dialysis hangover." Id.
This argument does not persuade us that the Examiner erred in
rejecting the claims as obvious. While Appellant discusses the disclosures
in Sundell and Navarro, Pupim expressly teaches that "PO [oral
supplementation] resulted in persistent anabolic benefits in the post-HD
[hemodialysis] phase for muscle protein metabolism." Pupim, Abstract
( emphasis added). Table 4 of Pupim shows that amino acids remained
above the control "post-HD" (Pupim 3153), the same effect Appellant
contends the inventor discovered (Appeal Br. 21: "the amino acids are
available after dialysis to increase circulating levels of amino acids in the
blood stream").
Appellant also argued that none of the applied prior art suggests
ameliorating post-dialysis washout as claimed. Appeal Br. 23. Appellant
contends that the Examiner is relying on the principle of inherency and that
"none of the applied documents recognizes the problem of post dialysis
washout, or even mentions it. The Examiner has not met the requisite prima
facie burden of establishing that the prior art discloses a method that is the
same or substantially the same as the claimed method." Id. at 23-24.
Appellant further argues that "the rejection has not established that the
claimed features necessarily must be present, or are the natural result of the
combination of elements explicitly disclosed by the prior art." Reply Br. 6.
We do not agree. Appellant contends that neither Sundell nor Pupim
achieve amelioration of post-dialysis washout as required by the preamble of
claim 1. Appeal Br. 24. However, Appellant has not provided objective
10
Appeal2018-005002
Application 14/692, 151
evidence to establish this fact. The issue is the obviousness of choosing a
time point within the claimed 45 minute to 2 hour interval post-dialysis in
which to administer the amino acid supplement. As explained above, it
would have been obvious to have optimized the time of amino acid
administration to achieve an improvement in amino acid loss ( catabolism)
and muscle wasting in patients undergoing hemodialysis. Pupim teaches the
desirability increasing amino acids post hemodialysis (fn.2), the same result
which Appellant has attributed to the claimed amelioration in post-dialysis
washout (Spec ,i 31 ):
[A] period of 20-40 minutes prior to the end of dialysis is best
for amelioration of the post-dialysis syndrome since it allows
time for the amino acids to be leached from the matrix and pass
out of the stomach and into the intestines, where they are then
picked up by the blood supply and circulated through the body
to the organs over the following 45 minutes.
Thus, the Examiner had a reasonable basis to believe that Pupim treated
"post-dialysis washout," even if it did not use the same language as recited
in the rejected claims.
Appellant contends that the claimed time period is critical to
achieving amelioration of post-dialysis washout, but do not provide any
evidence that the administration regimes carried out by either Sundell or
Pupim do not accomplish the same purpose. In particular, where Pupim
shows a post-dialysis effect on amino acids, it is Appellant's burden to show
that this effect was inadequate to ameliorate post-washout. In re Best, 562
F.2d 1252, 1254-55 (CCPA 1977).
While Appellant contends that none of the cited prior art recognized
the problem of post-dialysis washout, it was a known problem (Spec. ,i,i 2-
5). Nonetheless, on this record, we agree with Appellant that there is no
11
Appeal2018-005002
Application 14/692, 151
evidence that it was known that amino acids alleviated the post-dialysis
washout. However, if improving amino anabolism as described in Sundell
and Pupim accomplished the same result as claimed, then recognition of an
unappreciated result of following the same step in the prior art is not
sufficient to establish patentability. In re Baxter Travenol Labs., 952 F.2d
388, 391 (Fed. Cir. 1991). Appellant has not shown that the claimed interval
is critical in achieving the desired and unappreciated result, and that such
result was not obtained by either Sundell or Pupim. In other words,
Appellant did not establish that providing amino acids even closer to the end
of dialysis than Sundell or Pupim (210 and 90 minutes versus 45 minutes)
achieved a different result.
The Examiner is not relying on inherency as a basis for combining
Sundell, Pupim, and Navarro. Rather, the rejection is based on the premise
of optimizing the oral administration of amino acids during hemodialysis to
improve protein anabolism. Ans. 6. The Examiner properly placed the
burden on Appellant to show that the oral administration regimes described
in Sundell and Pupim did not alleviate post-dialysis washout at least to some
degree. The claims do not require any degree of improvement in post-
washout symptoms (Spec. ,i 16).
For the foregoing reasons, the obviousness rejection of claim 1 is
affirmed. Claims 11-15 fall with claim 1 because they were not separately
argued.
The Appeal Brief has separate sections for claims 7-10 (Appeal Br.
27), but the only substantive argument is the one made for claim 1.
Consequently, the obviousness rejection of claims 7-10 is affirmed for the
same reasons.
12
Appeal2018-005002
Application 14/692, 151
Claims 2-5
Claim 2 further recites "administering a group of at least two free
amino acids and/or their hydroxy or keto analogs." Claim 3-5 depend from
claim 2 and recite lists of specific amino acids. Sundell describes
administration of more than two amino acids (Sundell ,i 3). Pupim also
describes administration of more than two amino acids. Pupim 3150 (2nd
column, 2nd full paragraph).
Appellant states that "Pupim et al. does not administer a group of or
two or more free amino acids, but rather administers proteins and L-
Tryptophan," but this is not factually correct. Appeal Br. 25. Pupim
describes a composition comprising nine amino acids:
The following were the composition of essential AA
provided with the IDN and PO in grams, respectively,
isoleucine (2.962 and 3.011), leucine (4.113 and 5. 754), valine
(3.797 and 3.459), lysine (4.667 and 4.815), phenylalanine
(4.113 and 2.560), histidine (3.536 and 1.305), methionine
(2.962 and 1.513), threonine (2.962 and 3.286), and tryptophan
(0.989 and 0.873).
Pupim 3150 (2nd column, 2nd full paragraph).
Appellant also states the claimed amino acids are not described in the
cited publications, but failed to identify what amino acid is missing or
identify any other factual error in the rejection. A mere statement that a
claim limitation is not met by the prior art, when the Examiner found it to
be, is an improper attempt to put the burden on the Board to find the error.
The obviousness rejection of claims 2-5 are affirmed.
13
Appeal2018-005002
Application 14/692, 151
OBVIOUSNESS FURTHER BASED ON WOLFE
The Examiner rejected claims 11-20, further citing Wolfe to meet
limitations in dependent claims 16-20. Ans. 7-8. The Appeal Brief has
separately titled sections for the claims, but the only substantive argument is
the same one made for claim 1. Appeal Br. 28-32. In these sections,
Appellant identifies the limitations in the claims without explaining how the
limitations make the claims patentable over the cited prior art. It is not the
Board's burden to identify an error in the Examiner's rejection.
Accordingly, the rejection of claims 11-20 as obvious in view of Sundell,
Navarro, Pupim, and Wolfe is affirmed for the reasons set forth above and
those of the Examiner.
TIME PERIOD
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § l .136(a)(l )(iv).
AFFIRMED
14