Nutramax Laboratories, Inc.

Patent Trials and Appeals Board

Jun 29, 2020

14412189 - (D) (P.T.A.B. Jun. 29, 2020)

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.
14/412,189 12/30/2014 Brian Cornblatt 2043-809 7985
1009 7590 06/29/2020
KING & SCHICKLI, PLLC
800 CORPORATE DRIVE, SUITE 200
LEXINGTON, KY 40503
EXAMINER
NGUYEN, JOHN P
ART UNIT PAPER NUMBER
1619
NOTIFICATION DATE DELIVERY MODE
06/29/2020 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):
laura@iplaw1.net
uspto@iplaw1.net
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
__________

Ex parte BRIAN CORNBLATT, GRACE CORNBLATT,
ANTON BZHELYANSKY, ROBERT HENDERSON,
and RONALD KETTENACKER
__________

Appeal 2019-006022
Application 14/412,189
Technology Center 1600
__________

Before ERIC B. GRIMES, JEFFREY N. FREDMAN, and
RACHEL H. TOWNSEND, Administrative Patent Judges.

FREDMAN, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal1,2 under 35 U.S.C. § 134 involving claims to an oral
composition composed of magnesium and broccoli extract or powder. The
Examiner rejected the claims as obvious. We have jurisdiction under 35
U.S.C. § 6(b). We affirm.

1 We use the word “Appellant” to refer to “applicant” as defined in 37
C.F.R. § 1.42. Appellant identifies the Real Party in Interest as Nutramax
Laboratories, Inc. (see Appeal Br. 3).
2 We have considered and refer to the Specification of Dec. 30, 2014
(“Spec.”); Final Action of Sept. 7, 2018 (“Final Act.”); Appeal Brief of Feb.
19, 2019 (“Appeal Br.”); Examiner’s Answer of June 14, 2019 (“Ans.”); and
Reply Brief of Aug. 12, 2019 (“Reply Br.”).
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Statement of the Case
Background
“Oxidative stress plays a major role in aging, the progression of
neurodegenerative diseases as well as physiological trauma, such as
ischemia” (Spec. ¶ 7). “Antioxidant agents can reduce or inhibit the
oxidation of vital biomolecules and may play a role in treating, preventing,
or reducing the occurrence of conditions affected by oxidative stress” (id.).
“An example of a natural product thought to have chemoprotective and
antioxidant properties is sulforaphane. . . . The sulforaphane precursor,
glucoraphanin, can be obtained from vegetables of the Brassicaceae family,
such as broccoli, brussel sprouts, and cabbage” (id. ¶ 8). The Specification
also teaches that “[m]agnesium is a mineral that is important for many
systems in the body, including muscles and nerves” (id. ¶ 10).
The Claims
Claims 16–22, 26, and 27 are on appeal. Independent claim 16 is
representative and read as follows:
16. An orally administrable composition comprising a
synergistic combination of magnesium or a salt or complex
thereof and a broccoli extract or powder comprising one or both
of:
a sulforaphane; and
a sulforaphane precursor and an enzyme capable of
converting the sulforaphane precursor to sulforaphane;
the synergistic combination comprising the sulforaphane
or sulforaphane precursor and the enzyme and the magnesium
or a salt or complex thereof in amounts effective to decrease
levels or decrease gene expression of monocyte chemoattractant
protein-I (MCP-1) in a subject in need thereof.

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The Issues
A. The Examiner rejected claims 16, 18–20, 22, 26, and 27 under 35
U.S.C. § 103(a) as obvious over Siddiqui,3 Liang,4 and Starrett5 (Final Act.
4–7).
B. The Examiner rejected claims 17 and 21 under 35 U.S.C. § 103(a) as
obvious over Siddiqui, Liang, Starrett, and Talalay6 (Final Act. 7–9).

A. 35 U.S.C. § 103(a) over Siddiqui, Liang, and Starrett
The Examiner finds “Siddiqui discloses compositions comprising
sulphoraphane and minerals such as magnesium and vitamin C” and
“discloses the composition can be in tablet form” (Final Act. 5). The
Examiner acknowledges that Siddiqui “fails to disclose sulforaphane or
sulforaphane precursor and the magnesium or a salt or complex thereof in
amounts effective to provide synergy in decreasing levels or decrease gene
expression of MCP-1” (id.).
The Examiner finds “Liang discloses that sulforaphane reduces the
incidence of a number of forms of tumor” and “Liang teaches that
magnesium has a maximum inhibition on the formation of sulforaphane at 2
mM and that increasing the concentration of magnesium ion, the yield of

3 Siddiqui et al., US 6,511,675 B2, issued Jan. 28, 2003.
4 Liang et al., Effects of metal ions on myrosinase activity and the formation
of sulforaphane in broccoli seed, 43 J. Molecular Catalysis B: Enzymatic
19–22 (2006).
5 Starrett et al., Sulforaphane inhibits de novo synthesis of IL-8 and MCP-1
in human epithelial cells generated by cigarette smoke extract, 8 J.
Immunotoxicology 150–8 (2011).
6 Talalay et al., US 2009/0247477 A1, published Oct. 1, 2009.
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sulforaphane increased slightly” (Final Act. 5). The Examiner finds
“Starrett teaches that sulforaphane inhibits MCP-1 chemokine production
(e.g. decrease gene expression of MCP-1) induced by cigarette smoking”
(id.).
The Examiner finds the combination obvious “because magnesium is
known to increase production of sulforaphane from glucoraphanin (e.g.
sulforaphane precursor) in extracts of broccoli by myrosinase, and
sulforaphane is known to inhibit MCP-1 chemokine production (e.g.
decrease gene expression of MCP-1)” (Final Act. 6).
The issues with respect to this rejection are:
(i) Does a preponderance of the evidence of record support the
Examiner’s conclusion that the combination of Siddiqui, Liang, and Starrett
render claim 16 obvious?
(ii) If so, has Appellant provided evidence of unexpected results that
outweighs the evidence supporting the prima facie case of obviousness?
Findings of Fact
1. The Specification teaches the “sulforaphane precursor,
glucoraphanin, can be obtained from vegetables of the Brassicaceae family,
such as broccoli, brussel sprouts, and cabbage. . . . Glucoraphanin is
converted into sulforaphane by a thioglucosidase enzyme called myrosinase,
which occurs in a variety of exogenous sources such as Brassicaceae
vegetables and endogenously in the gut microflora” (Spec. ¶ 8).
2. The Specification teaches “the use of a broccoli extract and/or
powder, including but not limited to broccoli seed and sprout extracts and
powders . . . more preferably about 750 µg to about 400 mg . . . of the
broccoli extract” (Spec. ¶ 37).
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3. The Specification teaches the “magnesium or a salt or complex
thereof may be used. In some embodiments, the composition of the present
invention comprises about 1 to about 1000 mg” of magnesium (Spec. ¶ 44).
4. Example 6 of the Specification tested cells to measure MCP-1
levels after treatment with LPS and with “(i) DMSO (vehicle control), (ii)
0.5 μM SFN, (iii) 2.5 mM MgSO4, or (iv) the combination of 0.5 μM SFN
and 2.5 mM MgSO4” (Spec. ¶ 93). The Specification finds that “magnesium
sulfate alone resulted in an approximately 16% decrease, sulforaphane alone
resulted in an approximately 29% decrease, and the combination of
magnesium sulfate and sulforaphane resulted in an approximately 53%
decrease. This shows that the combination had a greater than additive effect
in reducing MCP-1 levels” (id. ¶ 94).
5. Siddiqui teaches “a dietary supplement containing an effective
amount of calcium, magnesium, folic acid, vitamins B6, B12, C, and E, and
phytochemicals comprising sulphoraphane” (Siddiqui 4:34–37).
6. Siddiqui teaches the dietary supplement “may be formulated
into tablets, powders, gels, or liquids” (Siddiqui 7:42–43).
7. Table 4 of Siddiqui is reproduced, in part, below:

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“Table 4 provides two additional embodiments of the invention, designated
as Formulae 2 and 3. These embodiments are exemplary only, and the
dosages may be altered without departing from the spirit and scope of the
invention” (Siddiqui 6:49–52; 7:1–30).
8. Liang teaches: “Glucoraphanin . . . a glucosinolate found in
broccoli . . . produces mostly sulforaphane . . . and nitrile when it is
hydrolyzed by myrosinase” (Liang 19, col. 1).
9. Liang teaches “[i]ncreasing the concentration of magnesium
ion, the yield of sulforaphane increased slightly” (Liang 21, col. 2).
10. Starrett teaches “[t]reatment with 5 μM SFN prior to the CSE
exposure significantly reduced the production of IL-8 and MCP-1” (Starrett
153, col. 2).
Principles of Law
“The combination of familiar elements according to known methods
is likely to be obvious when it does no more than yield predictable results.”
KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007). “If a person of
ordinary skill can implement a predictable variation, § 103 likely bars its
patentability.” Id. at 417.
Analysis
Prima facie obviousness
We adopt the Examiner’s findings of fact and reasoning regarding the
scope and content of the prior art (Final Act. 4–7; FF 1–10) and agree that
claim 16 is rendered obvious by Siddiqui, Liang, and Starrett. We address
Appellant’s arguments below.
Appellant contends “no teaching of Siddiqui even hints of any
synergistic effect of magnesium and sulforaphane or broccoli extract or
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powder comprising sulforaphane or a precursor on chemokine production as
required by the Appellant’s independent claims” (Appeal Br. 10).
We find this argument unpersuasive for several reasons. First,
Siddiqui teaches a composition of Formula 3 in Table 4 that is composed of
310 mg magnesium and 35 mg of broccoli sprout extract (FF 7). Siddiqui’s
composition contains an amount of magnesium falling within the 1 to 1000
mg magnesium range disclosed in the Specification (FF 3) and an amount of
broccoli extract within the 750 µg to about 400 mg disclosed in the
Specification (FF 2). Consequently, Siddiqui teaches an orally administrable
composition comprising both claimed components in amounts disclosed by
the Specification. (FF 2, 3, 7).7 Thus, the prior art composition appears to be
identical to that which is claimed to achieve a synergistic effect. “Using the
same composition claimed . . . in the same manner claimed . . . naturally
results in the same claimed . . . benefits.” Perricone v. Medicis Pharm.
Corp., 432 F.3d 1368, 1380 (Fed. Cir. 2005).
Second, as we address below in the unexpected results section, we are
not persuaded that the evidence supports a finding of unexpected results.
Appellant contends Siddiqui “provides a broad and unfettered
invitation to experiment but gives no other guidance to the skilled artisan in
arriving at the Appellant’s claimed subject matter” (Appeal. Br. 10).
Appellant cites a case for the proposition that “a prior art reference offering
‘a laundry list of potential active ingredients’ could not by itself properly

7 “It is well settled that ‘anticipation is the epitome of obviousness.”’ In re
McDaniel, 293 F.3d 1379, 1385 (Fed. Cir. 2002).
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support a finding of obviousness” (id.; citing Impax Labs. Inc. v. Lannett
Holdings Inc., 893 F.3d 1372, 1379 (Fed. Cir. 2018)).
We are not persuaded. In Impax, the text immediately following that
cited by Appellant explains the laundry list was composed of “‘over twenty-
five categories or examples of medications.’” Impax, 893 F.3d at 1379.
Impax also finds that the drug at issue “is mentioned once, with no further
mention in an example or claim.” Id.
In the current case, Siddiqui not only recites sulphoraphane, broccoli
extract, and magnesium multiple times but also provides a specific
formulation that includes broccoli extract and magnesium together (FF 5, 7).
Moreover, simply because the prior art “discloses a multitude of effective
combinations does not render any particular formulation less obvious.”
Merck & Co. v. Biocraft Labs., Inc., 874 F.2d 804, 807 (Fed. Cir. 1989).
Here, Siddiqui exemplifies three particular formulas: Formula 1 includes
sulphoraphane (see Siddiqui Table 1) and magnesium (see Siddiqui Table
3); Formula 2 has magnesium; and Formula 3 has both magnesium and
broccoli extract (FF 7). Thus, two of the three exemplified formulas include
the claimed ingredients. We do not find that Siddiqui represents a “laundry
list” situation but rather provides substantial guidance to a more limited set
of compositions that comprise sulphoraphane, broccoli extract, and
magnesium (see FF 5).
Appellant contends that the Examiner “has grossly misinterpreted the
teachings of Liang” and that “it cannot be fairly said that magnesium
‘improves’ conversion to sulforaphane because Liang expressly teaches that
at any concentration tested magnesium had a net negative effect on
conversion of glucoraphanin to sulforaphane when compared to 0 mM
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magnesium” (Appeal Br. 11–12). Appellant notes, regarding Liang, that
“synergy cannot rely on only slight or even additive effects of combinations
of compounds. Instead, synergy as demonstrated by the Appellant requires
more than simply an additive effect of a combination, i.e. a greater than
expected result” (id. at 13).
We agree with Appellant’s position that Liang does not provide a
reason to combine magnesium and glucoraphanin. However, we need not
rely upon Liang as supporting the obviousness analysis because Siddiqui
teaches the combination of components required by claim 16 (FF 7). We
note the Board may rely on less than all of the references applied by the
Examiner in an obviousness rationale without designating it as a new ground
of rejection. In re Bush, 296 F.2d 491, 496 (CCPA 1961).
We are not, however, persuaded that Liang teaches away from the
combination, because Liang does not address the impact of magnesium or
sulforaphane or their combination on MCP-1 levels as required by claim 16.
“Although a reference that teaches away is a significant factor to be
considered in determining unobviousness, the nature of the teaching is
highly relevant, and must be weighed in substance. A known or obvious
composition does not become patentable simply because it has been
described as somewhat inferior to some other product for the same use.” In
re Gurley, 27 F.3d 551, 553 (Fed. Cir. 1994). Here, it may be that
magnesium mildly reduces the conversion of glucoraphanin to sulforaphane,
but this does not detract from Siddiqui’s express teaching to use magnesium
and broccoli extract together in a single, exemplary formulation (FF 7) that
falls within the scope of claim 16.
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Appellant contends:
Due to the lack of any teaching or suggestion of synergy of
magnesium and sulforaphane in the asserted art combination
and the fact that the showing of synergy is only present on the
record in the Appellant’s specification, it logically follows that
motivation to combine has been improperly gleaned from the
Appellant’s own specification and that the combination of
Siddiqui, Liang, and Starrett is an exercise of impermissible
hindsight.
(Appeal Br. 14–15).
We find this argument unpersuasive. First, as noted above, Siddiqui
teaches a particular Formula 3 that comprises 310 mg magnesium (FF 7)
falling within the 1 to 1000 mg magnesium range disclosed in the
Specification (FF 3) and 35 mg broccoli extract (FF 7) falling within the 750
µg to about 400 mg disclosed in the Specification (FF 2). This express
disclosure by Siddiqui is not hindsight, but existed prior to Appellant’s filing
date (FF 5, 7).
Second, while Appellant correctly notes that the synergy limitation is
part of the claim, the “term ‘synergistically effective amount’ must mean
any amount that is synergistic.” Geneva Pharms., Inc. v. GlaxoSmithKline
PLC, 349 F.3d 1373, 1384 (Fed. Cir. 2003). Appellant relies upon
functional language and does not provide any specific details as to what
amounts constitute a “synergistic” amount that functions to decrease levels
or gene expression of MCP-1, though the Specification provides for ranges
of the claimed compounds that are within the scope of the invention.
Appellant provides a single in vitro example of a synergistic composition
composed of 0.5 μM sulforaphane and 2.5 mM MgSO4 (see FF 4). Notably,
the Specification describes microgram to milligram amounts for broccoli
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extract and milligram amounts for magnesium not molar amounts. Given
the quantities of the claimed ingredients identified as being within the scope
of the invention, the formula 3 composition of Siddiqui inherently satisfies
the functional synergistic recitation in claim 16, absent evidence to the
contrary. “Where, as here, the claimed and prior art products are identical or
substantially identical . . . the PTO can require an applicant to prove that the
prior art products do not necessarily or inherently possess the characteristics
of his claimed product.” In re Best, 562 F.2d 1252, 1255 (CCPA 1977).
Appellant has not provided any tests addressing the disclosure of Siddiqui.
Unexpected results
Appellant contends:
A clear showing is made that the combination of sulforaphane
and Mg had a synergistic effect on reduction in MCP-1 levels
compared to either sulforaphane or Mg provided alone.
Specifically, the combination of Mg and sulforaphane resulted
in an approximately 53% decrease in MCP-1 levels compared
to a 16% decrease in MCP-1 levels for Mg alone and a 29%
decrease for sulforaphane alone.
(Appeal Br. 9).
We are not persuaded by the asserted unexpected result for several
reasons. First, the data in the Specification is not compared with the closest
prior art, which would be formula 3 of Siddiqui that contains both
magnesium and broccoli extract (FF 7).8 See In re Baxter Travenol Labs.,

8 We note that because the amounts of magnesium and sulforaphane used in
Example 6 of the Specification are reported as concentrations (0.5 μM SFN,
2.5 mM MgSO4) without a disclosure of the volume added to cells, the
Specification provides insufficient information to determine what mass
amounts were used (i.e., milligrams or micrograms).
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952 F.2d 388, 392 (Fed. Cir. 1991) (“[W]hen unexpected results are used as
evidence of nonobviousness, the results must be shown to be unexpected
compared with the closest prior art.”).
Second, unexpected results must be “commensurate in scope with the
degree of protection sought by the claimed subject matter.” In re Harris,
409 F.3d 1339, 1344 (Fed. Cir. 2005). We are not persuaded that the results
are commensurate in scope with claim 16 because the results are drawn to a
single in vitro test employing 0.5 μM SFN and 2.5 mM MgSO4, and no
evidence that any other amount of these components would provide
synergistic reduction in MCP-1 levels. We note that claim 16 is open to any
amount of any type of magnesium salt, as well as any composition with any
amount of either sulforaphane or any sulforaphane precursor and an enzyme
that converts the sulforaphane precursor to sulforaphane, which when
combined results in synergism “to decrease levels or decrease gene
expression of” MCP-1.” One data point is insufficient to “to ascertain a
trend in the exemplified data which would allow [one having ordinary skill
in the art] to reasonably extend the probative value thereof.” In re Kollman,
595 F.2d 48, 56 (Fed. Cir. 1979).
Third, we are not persuaded that the data persuasively demonstrates
the results of Example 6 are actually synergistic, and that the results
represent a difference in kind rather than simply a difference in degree. We
note that levels of MCP-1 “were assessed via quantitative RT-PCR” and the
results are reported as a “percent of activated control.” (Spec. ¶ 93.) When
magnesium sulfate and sulforaphane are used together, the percent of
activated control is stated to be 53% while magnesium sulfate alone is
reported to be 16% and sulforaphane alone is reported to be 29% (FF 4).
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When the two claimed component’s values alone, 16% and 29%, are added,
the additive effect is 45%. Appellant does not explain why the change of
about 8%, from 53% to 45%, is a difference in kind rather than degree. We
find these results do “not represent a ‘difference in kind’ that is required to
show unexpected results.” In re Harris, 409 F.3d 1339, 1344 (Fed. Cir.
2005).
Indeed, Appellant provides no evidence that the difference between
53% and 45% is statistically significant. Appellant has not provided any
error bar in Figure 5 of the Specification, suggesting that the results
represent a single experiment, and therefore Appellant has not demonstrated
that the difference between 53% and 45% is reproducible and falls outside
the ordinary variation expected during experimentation. See McNeil-PPC,
Inc. v. L. Perrigo Co., 337 F.3d 1362, 1370 (Fed. Cir. 2003) (Finding
evidence unpersuasive that “was based on the results of a study involving
only nine participants and thus did not rise to the level of statistical
significance” and finding the studies were “not shown to be reproducible.”)
Conclusion of Law
(i) A preponderance of the evidence of record supports the
Examiner’s conclusion that the combination of Siddiqui, Liang, and Starrett
render claim 16 obvious.
(ii) Appellant has not provided evidence of unexpected results that
outweighs the evidence supporting the prima facie case of obviousness.

B. 35 U.S.C. § 103(a) over Siddiqui, Liang, Starrett, and Talalay
Appellant does not separately argue the rejection including Talalay
(see Appeal Br. 15). Having affirmed the obviousness rejection of claim 16
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over Siddiqui, Liang, and Starrett for the reasons given above, we also find
that the further combination with Talalay renders the dependent claims
obvious for the reasons given by the Examiner (see Final Act. 7–9).
CONCLUSION
In summary:
Claims
Rejected
35 U.S.C. §  Reference(s)/Basis Affirmed Reversed
16, 18–20, 22,
26, 27
103  Siddiqui, Liang,
Starrett
16, 18–20,
22, 26, 27

17, 21 103  Siddiqui, Liang,
Starrett, Talalay
17, 21
Overall
Outcome
16–22, 26,
27

No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a).

AFFIRMED