Ex Parte 5916912 et al

Board of Patent Appeals and Interferences

Sep 27, 2010

90007626 (B.P.A.I. Sep. 27, 2010)

UNITED STATES PATENT AND TRADEMARK OFFICE
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.
90/007,626 07/13/2005 5916912 B97-070-1RE
(BERK-061REX)
6890
84220 7590 09/27/2010
UC Berkeley - OTL
Bozicevic, Field & Francis LLP
1900 University Avenue, Suite 200
East Palo Alto, CA 94303
EXAMINER
HUANG, EVELYN MEI
ART UNIT PAPER NUMBER
3991
MAIL DATE DELIVERY MODE
09/27/2010 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
____________

Ex parte REGENTS OF THE UNIVERSITY OF CALIFORNIA
Appellant & Patent Owner
____________

Appeal 2010-007128
Reexamination Control 90/007,626
Technology Center 3900
Patent 5,916,912
____________

Before ROMULO H. DELMENDO, RICHARD M. LEBOVITZ, and
JEFFREY B. ROBERTSON, Administrative Patent Judges.

LEBOVITZ, Administrative Patent Judge.

DECISION ON APPEAL1

1 The two-month time period for filing an appeal or commencing a civil
action, as recited in 37 C.F.R. § 1.304, or for filing a request for rehearing,
as recited in 37 C.F.R. § 41.52, begins to run from the “MAIL DATE”
shown on the PTOL-90A cover letter attached to this decision.
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This is a decision on the appeal by the Patent Owner of U.S. Patent
No. 5,916,912 from the Patent Examiner’s rejections of claims 1, 2, 4-7, 9-
11, 16, 17, 20-23, 26-29, 37-40, 43-47, and 50-54 in an ex parte
reexamination proceeding. The Board’s jurisdiction in this appeal is derived
under 35 U.S.C. §§ 6(b), 134, and 306. We affirm-in-part.

STATEMENT OF THE CASE
U.S. Patent No. 5,916,912 (hereinafter “the ‘912 patent”) issued June
29, 1999. The named inventors are Bruce N. Ames and Tory M. Hagen.
The Patent Owner is the Reagents of the University of California. A
Request for Ex Parte Reexamination of claims 1-10 of the ‘912 patent was
filed by a Third-Party Requester (“Requester”) on July 13, 2005, pursuant to
35 U.S.C. §§ 302-307 and 37 C.F.R. § 1.510 (“Req.”). Reexamination was
sought on the basis of several prior art publications (Req. 2). Five different
rejections were proposed by the Requester (id.). One of the five proposed
rejections is at issue in this appeal.
We heard Patent Owner’s oral arguments on August 11, 2010, a
written transcript of which was entered into the record on September 14,
2010.
The claims of the issued patent were directed to methods for
increasing the metabolic rate of aged cells without a concomitant increase in
reactive oxygen species. The method involves administering carnitine and a
mitochondrially-active antioxidant, the latter which comprises a
metabolically-active thiol group. An orally-administratable dry unit dosage
comprising at least 250 mg of the carnitine and antioxidant was also
claimed. During the reexamination proceeding, the claims were amended to
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recite that a mitochondrially-active antioxidant was lipoic acid (LPA) or N-
acetylcysteine (claims 1 and 6). New claims were also added during the
proceeding. According to the ‘912 Patent, administration of the combination
of carnitine and LPA restored mitochondrial function and “reversed several
gross indicia of aging, including activity, muscle tone, coat appearance and
kidney morphology” in old animals. (‘912 Patent, col. 1, ll. 44-47.)
According to the Examiner, claims 1, 2, 4-7, 9-11, 16, 17, 20-23, 26-
29, 37-40, 43-47, and 50-54 are rejected (Ans. 4). Claims 13, 32, 34, and
57-59 were determined to be patentable (id.). All other claims, including
claims listed as “withdrawn” in the Appendix to the Appeal Brief, are
canceled (id. at 3-4).
The claims stand rejected under 35 U.S.C. § 103(a) as obvious in view
of Cavazza I2 and Packer3 (Ans. 5). Claims 1, 4, 5, 6, and 9 are
representative and read as follows (bracketing and underlining shows
amendments made during the reexamination proceeding):
1 A method for increasing the metabolic rate of aged cells
without a concomitant increase in metabolic production of
reactive oxygen species, comprising orally administering to a
mammalian host an effective dosage of at least about 10 mg/kg
host/day of a carnitine and at least about 10 mg/kg host/day of a
mitochondrially active antioxidant which physiologically
comprises a metabolically reactive thiol group, wherein the
antioxidant is N-acetylcysteine or lipoic acid.

4 A method for increasing the metabolic rate of aged cells
without a concomitant increase in metabolic production of

2 U.S. Patent 5,998,474 issued Dec. 7, 1999.
3 Lester Packer et al., Alpha-Lipoic Acid as a Biological Antioxidant, 19
Free Radical Biology & Med. 2, 227-250 (1995).
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reactive oxygen species, comprising orally administering to a
mammalian host an effective dosage of at least about 10 mg/kg
host/day of a carnitine and at least about 10 mg/kg host/day of a
mitochondrially active antioxidant which physiologically
comprises a metabolically reactive thiol group, [The method of
claim 1] wherein the antioxidant is lipoic acid.

5 The method of claim 1 wherein the carnitine is acetyl-L-
carnitine, the antioxidant is lipoic acid and the dosage is at least
about 100 mg/kg host/day each.

6 An orally administratable dry unit dosage comprising at least
about 250 mg of a carnitine and at least about 250 mg of a
mitochondrially active antioxidant which physiologically
comprises a metabolically reactive thiol group, wherein the
antioxidant is N-acetylcysteine or lipoic acid.

9 An orally administratable dry unit dosage comprising at least
about 250 mg of a carnitine and at least about 250 mg of a
mitochondrially active antioxidant which physiologically
comprises a metabolically reactive thiol group, [The dosage of
claim 6] wherein the antioxidant is lipoic acid.

REJECTION
The appealed claims stand rejected over Cavazza I and Packer.
Although Cavazza I issued after the June 16, 1997 filing date of the ‘912
patent, it has a US filing date of March 18, 1997, which is prior to the filing
date of the ‘912 patent. Cavazza I therefore qualifies as prior art under 35
U.S.C. § 102(e), in which “the [claimed] invention was described in . . . (2) a
patent [Cavazza I] granted on an application for patent by another filed in
the United States before the invention by the applicant for patent.” To
overcome the rejection of the claims over the combination of Cavazza I and
Packer, Appellant submitted three declarations under 37 C.F.R. § 1.131 by
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inventors Drs. Bruce Ames and Tory Hagen to antedate Cavazza I by
providing evidence of conception and diligence until reduction to practice of
the claimed invention.
Under 37 C.F.R. § 1.131:
(a) When any claim of an application or a patent under
reexamination is rejected, the inventor of the subject matter of
the rejected claim, the owner of the patent under reexamination,
or the party qualified under §§ 1.42, 1.43, or 1.47, may submit
an appropriate oath or declaration to establish invention of the
subject matter of the rejected claim prior to the effective date of
the reference or activity on which the rejection is based.

Prior invention may not be established under this section if . . . :
(1) The rejection is based upon a U.S. patent or U.S. patent
application publication of a pending or patented application to
another or others which claims the same patentable invention as
defined in § 41.203(a) of this title . . . .
The Examiner found that Cavazza I could not be antedated under 37
C.F.R. § 1.131(a)(1) because the ‘912 patent and Cavazza I were claiming
“the same patentable invention” (Ans. 10-11). The Examiner reached this
determination by applying the “two-way obviousness interference standard”
under 37 C.F.R. § 41.203(a), when “the subject matter of a claim of one
party would, if prior art, have anticipated or rendered obvious the subject
matter of a claim of the opposing party and vice versa.”
Appellant does not challenge the determination that the claimed
subject matter would anticipate or render obvious the patented subject matter
of Cavazza I. However, Appellant does challenge the conclusion that the
Cavazza I claims would render the claimed subject matter obvious in view
of Packer, the second “way” of the two-way test.
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There are two basic questions raised in this case: whether the ‘912
claims are obvious in view of the Cavazza I claims and Packer; and, in the
event that Cavazza I is not antedated by the section 1.131 declaration,
whether the ‘912 claims are obvious in view of the Cavazza I disclosure and
Packer. If the ‘912 claims are found to be obvious in view of the Cavazza I
claims and Packer, then it is unnecessary for us to reach the second
determination. However, since it did not appear that the Examiner required
the Cavazza I disclosure (the written description which preceded the claims)
to make the second obviousness determination, our decision herein applies
equally to the section 103(a) rejection of claims 1, 2, 4-7, 9-11, 16, 17, 20-
23, 26-29, 37-40, 43-47, and 50-54 in view of Cavazza I and Packer.

Issue
The issue is whether it would have been obvious to a person of
ordinary skill in the art to have selected LPA, as taught by Packer, as the
lipophilic antioxidant in the claims of the Cavazza I patent.

Legal Principles

[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.
Sakraida and Anderson’s-Black Rock are illustrative – a court
must ask whether the improvement is more than the predictable
use of prior art elements according to their established
functions.
KSR Int’l Co. v. Teleflex, Inc., 550 U.S. 398, 417 (2007).

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“The combination of familiar elements according to known methods
is likely to be obvious when it does no more than yield predictable results.”
Id. at 416.

Findings of Fact (“FF”)
Differences between the ‘912 patent’s (“Ames”) and Cavazza I claims
1. The differences between claim 4 of the ‘912 patent and claim 12 of
Cavazza I are as follows (App. Br. 14):

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2. The differences between claim 9 of the ‘912 patent and claim 1 of
Cavazza I are as follows (App. Br. 13):

3. Claims 8 and 11 of Cavazza I recite that the amount of L-carnitine
or an alkanoyl L-carnitine is 300-500 mg (0.3-05 g).
4. The claims of Cavazza I do not disclose an antioxidant that is LPA.

Packer
5. Packer is a review article titled “Alpha-Lipoic Acid as a Biological
Antioxidant” describing α-lipoic acid and its reduced form, dihydrolipoic
acid (DHLA).
6. “Many criteria must be considered when evaluating the antioxidant
potential of a compound” and “when considering preventative or therapeutic
applications” (Packer, pp. 227-28).
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7. Seven specific criteria for antioxidants are listed, but Packer
acknowledges that a “substance need not excel in meeting all these criteria
to be considered a good antioxidant.” (Packer, p. 228.)
8. Packer states: “An ‘ideal’ antioxidant would fulfill all of the above
criteria. The α-lipoic acid/dihydrolipoic redox couple approaches the ideal”
(id.). Citing a footnoted reference, Packer states that LPA “has been called
‘a universal antioxidant’” (id.).
9. Packer states: LPA is “probably rapidly converted to DHLA in
many tissues” (id.).
10. Characterizing the antioxidant properties of LPA and DHLA,
Packer states that “[b]ecause of these antioxidant attributes, a number of
experimental and clinical studies have been carried out which show α-lipoic
acid to be useful or potentially useful as a therapeutic agent in such
conditions as diabetes, ischemia-reperfusion injury, heavy-metal poisoning,
radiation damage, neurodegeneration, and HIV infection.” (Id. at 228-229.)
11. Summarizing published studies, Packer states: “[t]here is general
agreement about the antioxidant properties of” LPA (id. at 229). These
properties included:
- does scavenge singlet oxygen;
- does not appear to scavenge hydrogen peroxide;
- does not appear to scavenge superoxide radicals; and
- “probably” does not scavenge peroxyl radicals.
12. As to DHLA, Packer stated that it is a “potent antioxidant,
although there is more uncertainty as to its effects” (id. at 231).
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13. Based on published studies, Packer found that DHLA (Packer, pp.
231-232):
- does not appear to react with singlet oxygen;
- does not appear to react with hydrogen peroxide;
- controversial regarding its ability to scavenge superoxide radicals;
and
- scavenges peroxyl radicals.
14. DHLA was “shown to have both antioxidant and prooxidant
effects in which hydroxyl radical was generated; however, the prooxidant
effects, if real are probably due to DHLA’s effects on iron” (id. at 231).
15. After discussing various mechanisms, Packer concludes that “the
question of whether DHLA acts as a prooxidant in biological systems is yet
to be resolved.” (Id. at 233.)
16. Packer states that “it appears that” LPA and DHLA “act as
antioxidants not only directly, through radical quenching and metal
chelation, but indirectly as well, through recycling of other antioxidants and
possibly th[r]ough induction of increased intracellular levels of glutathione.”
(Id. at 235).
17. According to Packer, LPA “administration has been shown to be
effective in preventing pathology in various models in which reactive
oxygen species have been implicated.” (Id. at 237.)
18. Packer described experiments which “indicate that α-lipoic acid
in the diet has an antioxidant effect” (id. at 237).
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19. “In summary, α-lipoic acid is absorbed from the diet, transported
to the tissues, and taken up by cells where a large proportion is rapidly
converted to DHLA.” (Packer, p. 238.)
20. “The extent to which α-lipoic acid and DHLA are metabolized,
and the exact antioxidant/prooxidant balance of their metabolites, is yet to be
established. These metabolites may also play a significant role in the
observed effects of treatment with α-lipoic acid.” (Id. at 238.)
21. Packer summarizes beneficial effects of LPA in the treatment of
diabetes, neuropathy, ischemia-reperfusion, and other conditions (id. at 241
& 243).
22. One report described by Packer disclosed treatment of an animal
model of diabetes in which a single dose of 100 mg/kg body weight of LPA
was administered for one hour, or treated chronically with 30 mg/kg of LPA
for ten days (id. at 238-239).
23. Packer reported that mitochondria may be damaged by free
radicals which “may be responsible, in part for neurodegenerative diseases.”
(Id. at 244.)
24. Packer suggested that LPA “is a good candidate as an antioxidant
agent in neurodegenerative diseases. It can interrupt the chain at several
points: by competing for free transition metals as a chelator, by scavenging
hydroxyl or superoxide radicals, and by scavenging peroxyl radicals.” (Id.
at 244 (footnotes omitted).)
25. Packer noted that studies were underway to determine the effect
of LPA on degenerative diseases, and described “a recent study [which]
examined the effect of α-lipoic acid on memory loss in aging mice. Many
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species, including man, monkeys, rats, and mice, exhibit aging-related
cognitive deficits that may be caused, at least in part, by oxidative stress.”
(Packer, p. 244.)
26. Packer reported that LPA in 100 mg/kg body weight for fifteen
days improved performance on open-field memory tests in old but not young
mice (id.). “The authors concluded that α-lipoic acid’s free radical
scavenging ability may improve NMDA receptor density, leading to
improved memory.” (Id.)
27. Packer concluded:
Both α-lipoid acid and DHLA have substantial
antioxidant properties. These include their ability to directly
quench a variety of reactive oxygen species, inhibit reactive
oxygen species, and spare other antioxidants.
A number of experimental as well as clinical studies
point to the usefulness of α-lipoic acid as a therapeutic agent for
such diverse diseases as myocardial and cerebral ischemia-
perfusion injury, heavy-metal poisoning, radiation damage,
diabetes, neurodegenerative diseases, and AIDS.
(Id. at 246.)

Analysis
Claim 1 of Cavazza I is directed to a “composition for the prevention
or treatment of a disturbance or disease elicited by the oxidative stress
brought about by oxygen free radicals consisting of an L-carnit[i]ne or an
alkanoyl L-carnitine . . . with, independently, a lipophilic or hydrophilic
antioxidant.” (Cavazza, col. 5, ll. 50-57.) Claim 12 involves administering
the carnitine and antioxidant to prevent or treat disturbances or diseases
elicited by the oxidative stress brought about by oxygen free radicals. (Id. at
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col. 6, ll. 35-42.) The main difference between the Cavazza I claims and
those of the ‘912 patent is that Cavazza I does not claim that the antioxidant
is LPA (FF1&2) unlike in all the claims of the ‘912 patent.
However, finding that LPA was a known antioxidant with beneficial
effects in oxidative stress models and clinical conditions, and that it was
readily absorbed from the diet, the Examiner concluded that the ordinary
skilled worker would have been motivated to use LPA as a lipophilic
antioxidant in Cavazza I’s composition and treatment methods (Ans. 7-8).
Appellant contends that persons of ordinary skill in the art would not
have found the choice of LPA to be obvious. To support this position, first4
and second5 declarations by Simon Melov, Ph.D., an expert in the field of
aging and mitochondrial dysfunction, were provided. According to Dr.
Melov, the “genus of antioxidants is very large” containing “many hundreds
of different antioxidants” having “highly diverse” structures and functions
(2nd Melov Decl. ¶¶ 13-15; see also 1st Melov Decl. ¶ 10). Dr. Melov
contends that LPA was “not an art-recognized antioxidant at the Relevant
Time,” but was commonly thought of as a mitochondrial co-enzyme (2nd
Melov Decl. ¶ 15 & fn. 3) and it was not listed as an antioxidant in several
review articles about antioxidants (id. at fn. 3).
Dr. Melov also testified that the antioxidants utilized by Cavazza,
such as vitamin C, selenium, and glutathione, would not have reasonably

4 Declaration under 37 C.F.R. § 1.132, submitted Nov. 13, 2006 (hereinafter
“1st Melov Decl.).
5 Declaration under 37 C.F.R. § 1.132, submitted May 20, 2008 (hereinafter
“2nd Melov Decl.).

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suggested the choice of LPA (2nd Melov Decl. ¶¶ 13-15). Contrary to the
Examiner’s determination, Dr. Melov considered Packer’s disclosure not to
have reasonably suggested lipoic acid as an antioxidant in Cavazza I. Three
key reasons were given.
First, Dr. Melov stated that LPA would not have been considered an
obvious antioxidant variant of Cavazza I’s claims because LPA was
disclosed by Packer to scavenge “hydroxyl radicals, HOCl and singlet
oxygen, but [to be] . . . ineffective against superoxide radicals and hydrogen
peroxide, two of the most well-known oxidants.” (1st Melov Decl., ¶ 11;
see also 2nd Melov Decl. ¶ 19.)
Second, Dr. Melov testified that Packer reported that LPA was not
effective against peroxyl radicals, pointing away from its use as an
antioxidant (2nd Melov Decl. ¶ 20).
Third, Dr. Melov stated that Packer “conveys” to the skilled worker
that “the effect of lipoic acid in vivo as an antioxidant was not yet
established.” (Id. at ¶ 21.) The basis of this conclusion was that Packer
reported that LPA was converted into DHLA, and that the latter had
prooxidant properties that Packer said was of “serious concern in biological
systems.” (Id.)
We have considered both Melov declarations, but do not find them to
have persuasively established that persons of ordinary skill in the art would
not have been prompted to use LPA as an antioxidant in the claims of
Cavazza I.
Foremost, Packer reported many different studies in which LPA had
been described as an antioxidant and used in clinical studies for its
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antioxidant properties (FF10, FF11, FF16-18, FF21, FF24, F26, & FF27).
While it is true, as testified by Dr. Melov, that LPA was reported by Packer
not to scavenge hydrogen peroxide and superoxide (FF11), and probably not
peroxyl radicals (FF11), such deficiency in properties did not lead Packer to
conclude that LPA was not an antioxidant. To the contrary, Packer
expressly stated that “because” of the “antioxidant attributes, a number of
experimental and clinical studies have been carried out which show α-lipoic
acid to be useful or potentially useful as a therapeutic agent.” (FF10.)
Consistently, Packer recognized that a “substance need not excel in meeting
all” the ideal properties of an antioxidant “to be considered a good
antioxidant.” (FF7.) Thus, Packer characterized LPA as an antioxidant,
described its antioxidant properties, and attributed these properties to the
reason why certain clinical studies had performed with it.
Assuming that such clinical studies did not directly demonstrate the
efficacy of LPA to its antioxidant properties, as testified by Dr. Melov, we
still are unpersuaded that such a lack of evidence would have deterred the
skilled worker from using LPA in Cavazza I (2nd Melov Decl. ¶¶ 28 & 29).
Packer did not conclude that LPA’s antioxidant properties were not
responsible for the efficacy in treatment, but merely recognized that the
mechanism responsible for its action had not been proved. Despite the
failure of proof in certain studies, Packer still appeared to believe that LPA’s
antioxidant properties were a reason to use it clinically (FF23-24, 26, & 27).
In other words, after weighing all the published evidence, Packer expressed
clear support for the conclusion that LPA was an antioxidant with the ability
to directly quench a variety of reactive oxygen species, inhibit reactive
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oxygen species, and spare other antioxidants (FF27) – properties tied into
certain diseases and conditions, such as neurodegenerative disease (FF24).
Appellant urges that Packer taught the ordinary skilled worker that
LPA “is ineffective against two critically important oxygen species involved
in most types of oxidative stress, namely, superoxide and hydrogen
peroxide” (App. Br. 18 & 25; 1st Melov Decl. ¶ 11; 2nd Melov Decl.
¶ 19). For this reason, Appellant contends that it would not have been an
obvious choice as an antioxidant in the claims of Cavazza I.
The compositions and methods of Cavazza I are directed to
“prevention or treatment of a disturbance or disease elicited by the oxidative
stress brought about by oxygen free radicals.” (Cavazza, cl. 1, col. 5, ll. 50-
57.) Thus, the effect of LPA on oxygen free radicals is a factor a person of
ordinary skill in the art would have considered relevant in choosing an
antioxidant in the claims of Cavazza I.
Packer found that LPA was known to scavenge singlet oxygen
(FF11), that LPA had been “shown to be effective in preventing pathology in
various models in which reactive oxygen species have been implicated”
(FF17), had been used to treat conditions associated with oxidative stress
(FF25 & FF26), and had the ability to quench reactive oxygen species
(FF27). Accordingly, contrary to Appellant’s contentions, there were
compelling factual reasons to have selected LPA for precisely the type of
compositions administered in accordance with the claims of Cavazza I
patent.
Appellant also contends that there would not have been a reason to
choose LPA because it was not structurally related to any of the antioxidants
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in Cavazza was not recognized in many review articles as an antioxidant,
and was not well-established as an antioxidant (see 2nd Melov Decl. ¶ 15).
This conclusion is simply hard to reconcile with Packer’s review
article titled “Alpha-Lipoic Acid as a Biological Antioxidant.” From
reading Packer’s review article, it is evident that he reviewed published
literature on LPA, which included both positive and negative findings. For
example, in Table 1 on page 230, Packer shows two studies which found
peroxyl radicals to have been scavenged by LPA, and one study in which
they were not (see FF11&13). On the other hand, Packer reported four
studies that found singlet oxygen was scavenged by LPA (see FF11). Packer
considered this evidence, concluding that peroxyl was probably not
scavenged by LPA, but that singlet oxygen was. Thus, it is evident that
Packer reviewed the scientific literature on LPA, weighed it, and made
reasonable conclusions about what had been scientifically established about
LPA’s properties. In several instances, Packer indicated further work was
necessary to resolve an issue about its properties or that of DHLA (Packer at
231, col. 1; p. 233, col. 1, second full ¶). Yet, Packer still had reason to
characterize LPA as an antioxidant in the title and body of the article.
The claims in the Cavazza I patent literally and generically cover
lipophilic and hydrophilic antioxidants. While there may have been
hundreds of highly diverse antioxidants, as testified by Dr. Melov, the
claims in the Cavazza I patent still encompass them. The fact that there is a
long, highly diverse list of antioxidants does not make the description of
LPA as an antioxidant in Packer any less a disclosure. A species which is
specifically disclosed in a prior art reference is anticipatory even though it
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appears “without special emphasis in a longer list.” Perricone v. Medicis
Pharm. Corp., 432 F.3d 1368, 1376 (Fed. Cir. 2005). Although LPA may
be structurally different from certain specific antioxidants listed in the
Cavazza I claims, claim 1 of Cavazza claims the genus generically and
without structural limitation.
As held in KSR Int’l Co. v. Teleflex, Inc., 550 U.S. at 416, the
“combination of familiar elements according to known methods is likely to
be obvious when it does no more than yield predictable results.” When “a
patent ‘simply arranges old elements with each performing the same
function it had been known to perform’ and yields no more than one would
expect from such an arrangement, the combination is obvious.” Id. at 417
(quoting Sakraida v. AG Pro, Inc., 425 U.S. 273, 282 (1976)). The relevant
question is “whether the improvement is more than the predictable use of
prior art elements according to their established functions.” KSR at 417. In
this case, LPA was used for its known and established antioxidant
properties.
Quoting Packer’s statement about the prooxidant properties of DHLA
(FF15), Dr. Melov noted that Packer stated that DHLA could act as a
harmful prooxidant – apparently dissuading the skilled worker from using
the parent compound LPA in Cavazza I (2nd Melov Decl. ¶ 21).
Once again, while Packer made negative statements about certain
activities of DHLA and acknowledged that there are unresolved issues about
its properties, he also reported other studies in which antioxidant effects had
been observed (see Tbl. 2 on p. 232 of Packer; FF16).
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When the evidence is taken in its totality, the picture that emerges is
that Packer’s characterization of LPA as an antioxidant was made after his
careful consideration of both positive and negative experimental studies.
While not all the studies had shown LPA to be an antioxidant in every
condition nor to be a scavenger of all types of free radicals, the consensus
was – as reflected in Packer – that LPA had enough antioxidant properties to
have been considered useful in clinical studies as a therapeutic agent (FF10
& F27).

Dosages
The claims also recite specific dosages of carnitine and lipoic acid.
Method claims 1 and 4 require 10 mg/kg host/day of each of carnitine and
lipoic acid. Composition claims 6 and 9 are directed to a “dry unit dosage
comprising at least about 250 mg of” each of carnitine and lipoic acid.
Packer described studies in which LPA had been administered in
amounts of 100 mg/kg body weight and 30 mg/kg body weight, which the
Examiner found met the limitations of claims 1 and 4 (Ans. 21-22: FF22 &
FF26). Appellant challenged this determination only to the extent that
Packer did not describe administering the LPA in combination with carnitine
(Reply Br. 10). However, the Examiner did not rely on Packer for teaching
the claimed combination – only the LPA. Accordingly, this argument has no
merit.
As for the limitation which requires administration of 10 mg/kg
host/day of carnitine, the Examiner found this to have been met by Cavazza
I’s claims 11 and 12 when the carnitine was administered to a 50 kg host
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(Ans. 8). The Examiner’s determination is fact-based. Appellant did not
identify a specific defect in the Examiner’s findings or conclusion.
Given that daily dosages of LPA and carnitine were described in the
prior art, and that the daily dosage depends on a subject’s weight (Ans. 8), it
would have been obvious to a person of ordinary skill in the art to formulate
dosage units of suitable size to achieve the desired daily dosage, such as the
unit dosage size recited in claims 6 and 9. Furthermore, as found by the
Examiner, claims 8 and 11 of Cavazza I comprise 300-500 mg of carnitine
in a dosage unit, expressly meeting the limitations of claims 6 and 9 (Ans.
12).
We agree with Appellant that the dosages of vitamin C, as listed in
claim 11 of Cavazza I, would not have necessarily led the ordinary skilled
worker to choose the same amounts of LPA (App. Br. 21). However, while
we may disagree with the Examiner’s reasoning in this regard (Ans. 12-13),
for the reasons stated above, this does not change the determination that the
amounts of LPA recited in the claims would have been obvious to a person
of ordinary skill in the art.

Claim Preambles
The preambles of claims 1 and 4 are directed to methods “for
increasing the metabolic rate of aged cells without a concomitant increase in
metabolic production of reactive oxygen species.” Appellant contends that
none of the Cavazza I claims recite or suggest such a method (Reply Br. 10).
We do not interpret the claims to require that the recited carnitine and
lipoic acid be administered with the intent to increase the metabolic rate of
aged cells, as recited in the claim preambles. The intent or recognition that a
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method achieves a stated result does not change how the method is carried
out. See also Ex parte Batteux, Appeal No. 2007-0622, 2007 WL 5211675
(BPAI, Mar. 27, 2007) (Informative Opinion). Rather, the issue is whether
the steps of the claimed method, found to have been obvious over the
combination of the claims of Cavazza I and Packer, would have achieved the
result recited in the preamble. As the recited compounds and the amounts
administered were reasonably suggested by the prior art, the Examiner had
sound basis for believing that the same compounds in the same amounts
would increase the metabolic rate of aged cells.

Summary
After considering the evidence before us, we conclude that the
Examiner properly determined that the claims of the ‘912 patent were
obvious in view of the Cavazza I claims and Packer.

SECONDARY CONSIDERATIONS
In making an obviousness determination, we must consider (1) the
scope and content of the prior art; (2) the differences between the claimed
invention and the prior art; (3) the level of ordinary skill in the art; and (4)
any relevant secondary considerations, including commercial success, long
felt but unsolved needs, and failure of others. Graham v. John Deere Co.,
383 U.S. 1, 17 (1966).

Issue
Does Appellant’s evidence of secondary considerations outweigh the
Examiner’s case for obviousness of the claimed subject matter?
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Legal Principles
“For objective evidence to be accorded substantial weight, its
proponent must establish a nexus between the evidence and the merits of the
claimed invention.” In re GPAC, Inc., 57 F.3d 1573, 1580 (Fed. Cir. 1995).
“One way for a patent applicant to rebut a prima facie case of
obviousness is to make a showing of ‘unexpected results,’ i.e., to show that
the claimed invention exhibits some superior property or advantage that a
person of ordinary skill in the relevant art would have found surprising or
unexpected.” In re Soni, 54 F.3d 746, 750 (Fed. Cir. 1995).
“In order to establish unexpected results for a claimed invention,
objective evidence of non-obviousness must be commensurate in scope with
the claims which the evidence is offered to support.” In re Clemens, 622
F.2d 1029, 1035 (CCPA 1980). Finding the claim scope broad, and the
“probative value of appellants’ evidence . . . quite narrow,” the court
concluded this “is not a case in which the probative value of a narrow range
of data can be reasonably extended to prove the unobviousness of a broader
claimed range.” Id. at 1036. Cf. In re Kollman, 595 F.2d 48, 56 (CCPA
1979) (where it was held that the nonobviousness of a broader claimed range
was proven by a narrower range of data, when one having ordinary skill in
the art could “ascertain a trend in the exemplified data which would allow
him to reasonably extend the probative value thereof.”).
To overcome a finding of obviousness by demonstrating commercial
success, there must be a nexus between commercial success and the claimed
features. Ormco Corp. v. Align Tech., 463 F.3d 1299, 1312 (Fed. Cir. 2006).
“[T]he asserted commercial success of the product must be due to the merits
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of the claimed invention beyond what was readily available in the prior art.”
J.T. Eaton & Co. v. Atl. Paste & Glue Co., 106 F.3d 1563, 1571 (Fed. Cir.
1997).
“Denso argues that this [sales] evidence is insufficient because Tec
Air failed to provide market share data. Although sales figures coupled with
market data provide stronger evidence of commercial success, sales figures
alone are also evidence of commercial success.” Tec Air, Inc. v. Denso Mfg.
Mich., Inc., 192 F.3d 1353, 1361-62 (Fed. Cir. 1999).
“Although Huang’s affidavit certainly indicates that many units have
been sold, it provides no indication of whether this represents a substantial
quantity in this market. This court has noted in the past that evidence related
solely to the number of units sold provides a very weak showing of
commercial success, if any.” In re Huang, 100 F.3d 135, 140 (Fed. Cir.
1996).
The ultimate determination of whether an invention is obvious is a
legal question based on the totality of the evidence. Richardson-Vicks, Inc.
v. The Upjohn Co., 122 F.3d 1476, 1483 (Fed. Cir. 1997). Commercial
success and unexpected results, although supported by substantial evidence,
did not overcome a strong case of obviousness. Id. at 1484. See also Brown
& Williamson Tobacco Corp. v. Philip Morris, Inc., 229 F.3d 1120, 1131-32
(Fed. Cir. 2000).
Findings of Fact (“FF”)

Inventors’ 37 C.F.R. § 1.131 Declaration
28. “Dosages of about 100 mg/kg/day for rats roughly convert to
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15 mg/kg/day for human[s].” (Supp. 37 C.F.R. § 1.131 Decl. of Bruce N.
Ames & Tory M. Hagen, ¶ 21, submitted Nov. 13, 2006 (footnote omitted).)
29. “Dosages of 82.5 mg/kg/day for rats roughly convert to about 12
mg/kg/day for human[s].” (Id.)

Hagen6
30. Hagen discloses administering a daily LPA dose of 0.075 g/kg
body weight for old rats (Hagen, p. 1871, col. 1). This value is equivalent to
75 mg/kg body weight/day.
31. Hagen discloses administering a daily carnitine dose of 0.75 g/kg
body weight for old rats (id.). This value is equivalent to 750 mg/kg body
weight/day.
32. Hagen stated that, in rats, “[f]eeding ALCAR [acetyl-L-carnitine]
in combination with LA [alpha lipoic acid] increased metabolism and
lowered oxidative stress more than either compound alone.” (Id. at 1870,
Abstract.)
33. Hagen stated that LA may act synergistically with ALCAR to
improve mitochondrial-supported bioenergetics and antioxidant status (id. at
1874, col. 2).

6 Tory M. Hagen et al., Feeding Acetyl-L-Carnitine and Lipoic Acid to Old
Rats Significantly Improves Metabolic Function while Decreasing Oxidative
Stress, 99 Proc. Nat’l Acad. Sci. of the U.S.A. 4, 1870-1875 (2002).
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Liu7
34. Liu concluded “that feeding old rats ALCAR and/or LA improved
performance on memory tasks, reduced brain mitochondrial structure decay,
and reduced oxidative damage in the brain. The combination of ALCAR
and LA showed a greater effect than ALCAR or LA alone.” (Liu, p. 2361,
col. 1).
35. According to Figure 2, in which improvements in memory were
shown, rats were administered 0.2% LA (wt/wt) and 0.5% (wt/vol) of
ALCAR (id. at 2358).
36. The Examiner did not make findings about the equivalency of the
amounts of LPA and carnitine fed to the rats and the daily dosage in
mg/kg/day.
37. Appellant did not establish the equivalency of the amounts of
LPA and carnitine fed to the rats and the daily dosage in mg/kg/day.

Cavazza II8
38. Cavazza II disclosed that the combination of carnitine and LPA
achieves “surprising” and “synergistic” results in a number of different tests
(Cavazza II, col. 5, ll. 5-11; col. 6, ll. 43-45; col. 8, ll. 20-25), including:

7 Jiankang Liu et al., Memory Loss in Old Rats is Associated with Brain
Mitochondrial Decay and RNA/DNA Oxidation: Partial Reversal by
Feeding Acetyl-L-Carnitine and/or R-α-Lipoic Acid, 99 Proc. Nat’l Acad.
Sci. U.S.A 4, 2356-2361(2002).
8 U.S. Patent 6,365,622 B1 issued Apr. 2, 2002.
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39. • 50 mg/kg carnitine and 20 mg/kg LPA in neuroprotective
activity tests in an experimental cerebral ischaemia test (Cavazza II, col. 4, l.
65 to col. 5, l. 2);
40. • 200 mg/kg carnitine and 50 mg/kg LPA in experimental diabetic
hyperglycaemia tests (id. at col. 6, ll. 1-15);
41. • 100 mg/kg carnitine and 25 mg/kg LPA in a test of sorbitol
content in the ocular lens and sciatic nerve of the diabetic rat (id. at col. 6, ll.
30-33; Table 3);
42. • 200 mg/kg carnitine and 50 mg/kg LPA in sciatic nerve
regeneration tests in diabetic rats (id. at col. 7, ll. 64-67).

Milgram9
43. Daily oral doses of 11 mg/g LPA and 27.5 mg/kg acetyl-L-
carnitine were provided in capsules to beagle dogs (Milgram, p. 3757, col.
2).
44. The dogs “made significantly fewer errors in reaching the
learning criterion on two landmark discrimination tasks compared to
controls administered a methylcellulose placebo.” (Id. at 3756, Abstract.)
45. Milgram reported that the combination of carnitine and LPA
improved landmark discrimination tests in beagle dogs, but did not compare
the combination to carnitine or LPA, alone.

9 N.W. Milgram et al., Acetyl-L-carnitine and α-lipoic Acid Supplementation
of Aged Beagle Dogs Improves Learning in Two Landmark Discrimination
Tests, 21 J. Fed’n Am. Soc’y Experimental Biology 13, 3756-3762 (2007).
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Commercial Success
46. Juvenon CHS contains “500 mg Acetyl-L-Carnitine and 200 mg
Alpha Lipoic Acid in one tablet. The suggested use is 2 tablets per day,
namely 1000 mg Acetyl-L-Carnitine and 400 mg Alpha Lipoic Acid per
day.” (Hamilton Decl. ¶ 7).
47. The amounts of LPA in the tablet do not meet the claimed amount
of at least 250 mg.
48. “Since the initial launch of Juvenon CHS, its sales have increased
dramatically. In 2002, the sales revenue of Juvenon CHS was $230,900 (7
month[s]) or a monthly average of $32,986. By 2007, the revenue of the
product had risen substantially to $ 7,566,604 (12 months), or a monthly
average of $630,550. Exhibit N2 provides a summary of the percentage
growth of the product revenues from years 2003 to 2007 in comparison to
the year of 2002.” (Id. at ¶ 8.)
49. The “sales of Juvenon CHS in 2007 were more than twice the
retail sales of lipoic acid alone based on the most recently available industry
sales report.” (Id. at ¶ 9 (footnote omitted).)

Recognition
50. Dr. Melov provided evidence from a variety of sources that Drs.
Ames’ and Hagen’s results with carnitine and LPA were recognized as
important and met with enthusiasm. These include licensing requests,
reports in industry articles (1st Melov Decl. ¶¶ 32, 34, & 35; Hamilton Decl.
¶ 10), news reports (id. at ¶ 33), and journal articles by peers (id. at ¶¶ 36-
39).
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51. For example, Dr. Mark Hyman, the editor of Alternative
Therapies, stated that, based on Ames’ work, “we can now address the
mitochondria1 oxidative decay that is characteristic of age (and many
chronic diseases) by providing normal mitochondria metabolites such as
acetyl-carnitine and lipoic acid at high doses.” 10 (Hyman, p. 92, col. 1.)

Analysis
Once a prima facie case of obviousness has been established,
Appellant can rebut the case with evidence of secondary considerations. In
this case, Appellant responded to the Examiner’s case with several lines of
evidence involving unexpected results (synergy), commercial success, and
recognition by the industry and peers (including licensing, copying, and
fulfilling long-felt, unmet need).
In weighing the totality of the evidence provided by Appellant, it is
necessary to recognize that the evidence must have a relationship to the
subject matter that is claimed. In patent parlance, this is often called the
“nexus” to mean the connection between the claims and the secondary
considerations of nonobviousness. In re GPAC, Inc., 57 F.3d at 1580. In
other words, the secondary considerations must show that the claimed
subject matter, including its specifically recited features, would not have
been obvious to a person of ordinary skill in the art. Here, there are three
main types of claims with specific features, each which requires

10 Mark A. Hyman, Paradigm Shift: The End of “Normal Science” in
Medicine: Understanding Function in Nutrition, Health, and Disease, 10
Alternative Therapies 5, 10-15 & 90-94 (2004).
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consideration when weighing the evidence of obviousness with the evidence
of non-obviousness.
1. Claims 1 and 4 are methods that involve orally administering
dosages of “at least about 10 mg/kg host/day” of each of carnitine and LPA.
2. Claim 5 is a method that involves orally administering dosages of
“at least about 100 mg/kg host/day” of each of carnitine and LPA.
3. Claims 6 and 9 are directed to an “orally administratable dry unit
dosage comprising at least about 250 mg” of a carnitine and lipoic acid.
For evidence to support a non-obviousness determination, it must
address and have a relationship to the specific limitations in the claims.

Claim 5
We begin with the claim in which the secondary considerations of
non-obviousness outweigh the case of obviousness in view of the claims of
Cavazza I and Packer: Claim 5.
Because claim 5 involves administering “at least about 100 mg/kg
host/day” of each of carnitine and LPA, we look to the evidence to
determine whether it showed that the recited claim dosage would have been
non-obvious to persons of ordinary skill in the art.
In this case, there are multiple data points which show evidence of
synergy for the combination of carnitine and LPA in the claimed dosage, “at
least about 100 mg/kg host/day.” Synergy, as defined by the Examiner, is
when the observed effect is greater than the additive effects of LPA and
carnitine taken separately (Ans. 28). These include:
• Hagen’s of 750 mg/kg carnitine and 75 mg/kg LPA (FF30-33); and
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• Cavazza II’s of 50-200 mg/kg carnitine and 20-50 mg/kg LPA
(FF38-42).
The amount of carnitine administered in these publications overlaps
with that administered in the claimed range, establishing that dosages of
carnitine within the claimed range behaved synergistically in combination
with LPA.
For LPA, synergy was shown for amounts in the range of 20-75
mg/kg/day. While such amounts do not meet the 100 mg/kg host/day, they
are nonetheless sufficient to establish a trend – beginning at 20 mg/kg/day –
that increasing amounts of LPA produce synergistic effects when combined
with carnitine. In re Clemens, 622 F.2d at 1035; In re Kollman, 595 F.2d at
56. Moreover, Hyman provides evidence that high doses of carnitine and
LPA address the mitochondria1 oxidative decay that is characteristic of age
(FF51; 2nd Melov Decl. ¶ 48). As values below 100 mg/ kg host/day were
found to be synergistic, persons of ordinary skill in the art would have
reasonably expected that higher dosages would have the same effect.

Claims 1 and 4
Synergy
Claims 1 and 4 require about tenfold less of each of carnitine and LPA
than in claim 5. The evidence does not show that the claimed dosages were
responsible for synergy.
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Hagen makes at least one clear statement in its publication about
synergy between LPA and carnitine.11 In the Discussion section, Hagen
stated that LPA may act synergistically with carnitine to improve
mitochondrial-supported bioenergetics and antioxidant status (FF33), both
conditions which the ‘912 patent appears to relate to improving the
metabolic rate of aged cells required by the preambles of claims 1 and 4.
Dr. Melov also testified that Hagen showed synergy in some experiments
(2nd Melov Decl. ¶ 47). Moreover, Dr. Melov testified that the Hagen
publication “was listed as one of the top twenty five scientific papers” in
Dietary Supplement Research 2002 (1st Melov Decl. ¶ 36). Based on these
published statements in Hagen, Dr. Melov’s testimony, and peer recognition
of the Hagen publication, we will give credit to the fact that synergy was
established for the combination of carnitine and LPA for specific dosage
ranges.
The Examiner argued that such synergy would have been expected
based on Packer’s statement that LPA interacts with and spares other
antioxidants in an in vivo system (Ans. 29). However, Packer did not test
nor address the combination of carnitine and LPA. Nor did the Examiner
give a scientific reason as to why LPA, when combined with carnitine,
would have been expected to produce more than additive results. Thus, we
do not agree that the results obtained in the Hagen publication would have
been expected.

11 In the Abstract, Hagen states that carnitine and LA increased metabolism
and lowered oxidative stress more than either compound alone (FF32), but
this statement does not indicate that the effective was non-additive.
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Unexpected results must be commensurate in scope with the claimed
subject matter. In this case, for claims 1 and 4, the results must be
representative of the claimed dosages of “at least about 10 mg/kg host/day.”
Appellant did not make a clear statement about whether the dosages
administered in Hagen to rats met the claimed range. Nonetheless, the
Examiner did not question whether the amounts administered by Hagen met
the claimed range (Ans. 30). Rather, the Examiner argued that the
unexpected result should be limited to only those values disclosed in Hagen
that were shown to be synergistic and not to the entire dosage range which is
claimed (id.). The issue therefore is whether the synergistic results in Hagen
can be extended to other values in the claimed range. In re Clemens, 622
F.2d at 1035.
The problem with the evidence is that Appellant did not describe a
correlation between the amounts of carnitine and LPA that achieved synergy
in the Hagen publication with the claimed dosages of “at least about 10
mg/kg host/day.” Based on the values in Hagen for rats, it appears that the
values of LPA and carnitine administered were 75 mg/kg/day and 750
mg/kg/day, respectively, higher than the claimed dosages (FF30 & FF31).
Appellant has not shown that dosages as low as 10 mg/kg host/day were
synergistic nor that synergy would have been reasonably expected at the
lowest end of the claimed range. The exemplified data of one point, which
is at least sevenfold higher than the lower limit of the claimed dosage
spectrum (75 versus 10), is insufficient to ascertain a trend for those values
that are less than 75 mg but more than 10 mg. Consequently, the Hagen
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publication does not establish unexpected results for the complete scope of
the claims.
Liu is also deficient. While Dr. Melov asserted that synergy was
observed in memory tests when old rats were administered carnitine and
LPA, Appellant did not establish that the administered amounts met the
claimed range of at least 10 mg/kg/day. Consequently, this evidence does
not support synergy for any part of the claims 1 and 4.
Milgram reported that the combination of carnitine and LPA
improved landmark discrimination tests in beagle dogs. The dosages were
close to the claimed value of 10 mg/kg/day (FF42). However, Milgram did
not compare the combination to carnitine or LPA, alone. It therefore cannot
be ascertained whether Milgram’s results were non-additive and synergistic.
Consistently, Mr. Hamilton described Milgram’s study, but made no such
statement about synergy (Hamilton Decl. ¶ 15).

Commercial success
For a number of reasons, we conclude that the evidence of
commercial success is weak. The evidence for commercial success was
based on the sales of the Juvenon product comprising 500 mg acetyl-L-
carnitine and 200 mg alpha-lipoic acid (FF46).
Mr. Hamilton testified that sales of Juvenon increased dramatically
from 2002 to 2007 (FF48). However, the reason for this increase was not
explained. For example, increased sales can result from marketing
strategies, co-branding and joint marketing (Hamilton Decl. ¶ 11), and
number of sales personnel, rather than simply product demand because of a
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claimed feature. Mr. Hamilton reported that the sales of Juvenon were more
than twice the retail sales of LPA (FF49), but did not do the same for
carnitine – a required element of the claims. Thus, Appellant did not
establish that the claimed product captured a market share of both lipoic acid
and carnitine sales. Sales figures alone are weak evidence of commercial
success, if any. See Tec Air, Inc. v. Denso Mfg.Mich., Inc., 192 F.3d. at
1361-62; In re Huang, 100 F.3d at 140.
Nonetheless, we do not agree with the Examiner’s assertion that the
recommended dosage (FF46) does not fall within or close to the scope of the
method claims. For example, assuming an individual with a weight of 50 kg
(110 pounds) (Ans. 33), the recommended doses of 400 mg per day of LPA
and 1000 mg per day of carnitine would be equivalent to 8 mg/kg/day and
20 mg/kg/day, respectively, close to or within the scope of claims 1 and 4.

Licensing/copying
Mr. Hamilton testified that twenty-three companies approached his
company for licensing opportunities (Hamilton Decl. ¶ 10) and that his
company co-branded and jointly marketed its Juvenon product with a
leading company (id. at ¶¶ 11-12). However, the mere existence of licenses
is insufficient to overcome the conclusion of obviousness with a showing of
nexus. Iron Grip Barbell Co., Inc. v. USA Sports, Inc., 392 F.3d 1317, 1324
(Fed. Cir. 2004).
Evidence of copying of the product was also provided. (See Ex. N9.)
However, at least one of these products had components in addition to the
carnitine and LPA, i.e., raspberry extract, Berry ORAC, Comprehensive
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Green Mix, and MSM (Ex. 18). Thus, it is not evident that the Juvenon
product was directly copied in each case.

Recognition
In addition to the synergy results, there was also evidence of
recognition by peers and the industry. With respect to the peer recognition,
we note that Dr. Mark Hyman, editor of Alternative Therapies, referred to
Drs. Ames’ and Hagen’s work in his article, but he very specifically
described it in the context of providing “acetyl-carnitine and lipoic acid at
high doses.” (FF49.) According to Appellant, these high dosages are, in
part, involved in the synergistic effects between carnitine and LPA (Reply
Br. 14; 2nd Melov Decl. ¶ 48). It is unclear on this record what
administered dosages constitute high doses. As discussed in the previous
section, we recognized that higher dosages of 100 mg/kg/day produce
synergy. However, this is less than clear with the tenfold lower amounts
recited in claims 1 and 4. Appellant did not establish that the high doses
mentioned in Dr. Hyman’s article were representative of the dosages recited
in claims 1 and 4.
Dr. Melov also provided numerous articles and industry licensing as
evidence that the combination was recognized as important. However, the
issue is whether the claimed invention was recognized – and the claimed
invention here involves, inter alia, the amounts of at least 10 mg/kg/day.
Some of the article appear to involve the actual product (1st Melov Decl. ¶
32) while some appear to be commenting on published journal articles
including those which have been considered here (id. at ¶ 33). Overall, the
evidence clearly demonstrates that Ames’ and Hagen’s work generated
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serious interest in the industry and attracted the attention of their peers, but it
is not clear on this record that the enthusiasm and recognition espoused in
those publications reflected the success of a method of administering
amounts of 10 mg/kg host/day (and the unit dosages with at least 250 mg).
At least some of this recognition was based on publications which have not
clearly been shown to follow the 10 mg/kg host/day regime (such as the
Hagen publication) and a peer in the industry (Dr. Hyman) explicitly
referred to high doses of the carnitine and LPA.

Summary
We conclude that Appellant’s secondary considerations are
insufficient to overcome the strong case of obviousness for the claims
reciting “10 mg/ kg body/day” and “at least 250 mg” of the carnitine and
lipoic acid components in view of the Cavazza I claims and Packer.
First, as discussed above, there was no evidence of synergy for the
claimed range of “10 mg/ kg body/day,” although we found such evidence
for higher dosages of the two claimed components.
Second, in one of the peer written articles, the author explicitly
mentioned high doses of carnitine and lipoic acid associated with addressing
mitochondrial oxidative decay, indicating that peers of the inventors
believed that high dosages were responsible for the benefits of the claimed
components.
Third, while there was evidence of an increase in sales of the Juvenon
product comprising carnitine and lipoic acid, there was no evidence of
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market share for both components. Consequently, we do not consider the
commercial success to be a strong showing.
On the other hand, the obviousness case is based on strong factual
evidence. Packer expressly teaches LPA’s use in various experimental and
clinical conditions, including as an antioxidant in neurodegenerative diseases
(FF24), and its use and suggested use to improve memory deficits and other
cognitive deficits associated with oxidative stress (FF25 & 26). Thus,
LPA’s efficacy in treating conditions associated with oxidative stress, as
recited in the Cavazza I claims, was known in the prior art. Similarly,
Cavazza I teaches the use of carnitine to treat or prevent disturbances or
diseases elicited by oxidative stress (claim 12). As both LPA and carnitine
were known to treat oxidative stress disorders, it appears that the features of
the claimed invention were readily available to one of ordinary skill in the
art.
In reaching this determination, we have considered all of Appellant’s
evidence – including the copying, licensing, long-felt need, and recognition.
However, when summed up and weighed against the strong case of
obviousness, it does not outweigh our concerns about the lack of nexus
between the showings and the limitations recited in claims 1, 4, 6, and 9. In
re Huang, 100 F.3d 135 at 1484; Brown & Williamson Tobacco Corp., 229
F.3d at 1131-32.

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CONCLUSION
The evidence of secondary considerations, when considered in view
of the totality of evidence before us, did not outweigh the Examiner’s
determination that claims 1, 2, 4, 6, 7, 9-11, 16, 17, 20-23, 26-29, 37-40, 43-
47, and 50-54 are obvious in view of the claims of Cavazza I and Packer.
Accordingly, we affirm the obviousness rejection of claims 1, 2, 4, 6, 7, 9-
11, 16, 17, 20-23, 26-29, 37-40, 43-47, and 50-54. See 37 C.F.R
41.37(c)(1)(vii) for those claims not argued separately.
The obviousness rejection of claim 5 is reversed because the evidence
of secondary considerations, when considered in view of the totality of
evidence before us, outweighed the Examiner’s obviousness determination.

TIME PERIOD FOR RESPONSE
Requests for extensions of time in this ex parte reexamination
proceeding are governed by 37 C.F.R. § 1.550(c). See 37 C.F.R. § 41.50(f).

AFFIRMED-IN-PART

bim

Appeal 2010-007128
Reexamination Control 90/007,626
Patent 5,916,912

39
FOR THE APPELLANT:

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FOR THE THIRD PARTY REQUESTER:

HOFFMAN, WASSON & GILTER, PC
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