Ex Parte Stanley et al

Patent Trial and Appeal Board

Jun 9, 2017

12250624 (P.T.A.B. Jun. 9, 2017)

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.
12/250,624 10/14/2008 Richard Thomas Stanley SR. HSPH-001/03US
311306-2003
4103
58249 7590 06/13/2017
COOLEY LLP
ATTN: Patent Group
1299 Pennsylvania Avenue, NW
Suite 700
Washington, DC 20004
EXAMINER
KASSA, JESSICA M
ART UNIT PAPER NUMBER
1616
NOTIFICATION DATE DELIVERY MODE
06/13/2017 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):
zpatdcdocketing@cooley.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte RICHARD THOMAS STANLEY SR., DAVID EDWARD
STANLEY, MARCUS BLACKSTONE, and THOMAS WAGNER
Appeal 2017-005497
Application 12/250,6241
Technology Center 1600
Before ERIC B. GRIMES, JOHN G. NEW, and RACHEL H. TOWNSEND,
Administrative Patent Judges.
TOWNSEND, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35U.S.C. § 134 involving claims to a method
of treating cancer by administering a silicate that liberates orthosilicic acid in
vivo, which have been rejected as obvious. We have jurisdiction under 35
U.S.C. § 6(b).
We reverse.
STATEMENT OF THE CASE
Claims 1, 5, 26, 27, and 29-44 are on appeal. Claims 1 and 36 are
representative and read as follows:
1 Appellants identify the Real Party in Interest as HS Pharmaceuticals, LLC.
(Appeal Br. 2.)
Appeal 2017-005497
Application 12/250,624
1. A method of treating a cancer comprising administering to a
subject in need of treatment for a cancer a composition
comprising a solution of an active agent, wherein the active
agent comprises a silicate that liberates orthosilicic acid in vivo,
wherein the solution has a pH of about 6.0-8.0, the active agent
is present at a concentration of about 1—5 mg/mL, and wherein
said cancer is a melanoma; a sarcoma; a carcinoma of the lung,
breast, ovary, stomach, pancreas, larynx, esophagus, testes,
liver, parotid, biliary tract, colon, rectum, cervix, uterus,
endometrium, kidney, bladder, prostate, or thyroid; a squamous
cell carcinoma; a small cell carcinoma; glioma; or
neuroblastoma.
(Appeal Br. 13.)
36. A method of treating a cancer comprising administering to
a subject in need of treatment for a cancer a composition,
wherein the composition is prepared by a method consisting
essentially of forming an aqueous solution of an active agent
consisting of an orthosilicic acid salt and adjusting the pH of
said solution to about 6.0-8.0;
wherein said cancer is a melanoma; a sarcoma; a
carcinoma of the lung, breast, ovary, stomach, pancreas, larynx,
esophagus, testes, liver, parotid, biliary tract, colon, rectum,
cervix, uterus, endometrium, kidney, bladder, prostate, or
thyroid; a squamous cell carcinoma; a small cell carcinoma;
glioma; or neuroblastoma.
{Id. at 14.)
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Application 12/250,624
The following ground of rejection by the Examiner is before us on
review:
Claims 1, 5, 26, 27, and 29-44 under 35 U.S.C. § 103(a) as
unpatentable over Busch,2 Juturu,3 Le,4 and Choi.5
DISCUSSION
The Examiner finds that Busch discloses that it was known to use
silicic acid therapy in treating carcinoma by administering metasilicate of
sodium, i.e., Na2Si03, and that it is beneficial “in as much as it reaches the
tissues of the lungs and deposits therein silicic acid.” (Final Action 3.) The
Examiner finds that Busch developed a different composition in which to
deliver silicic acid that solved the problems of the prior art composition with
respect to pH and agglomeration; the composition being pure metasilicate of
sodium “combined with . . . casein or albuminates of animal or similar
albuminous matter.” (Ans. 14; Final Action 3.) The Examiner notes that the
Busch composition is “easily absorbed by the mucous membranes.” (Final
Action at 6.) The Examiner notes that Na2SiC>3 is the same active ingredient
disclosed in the specification for use in a method of treating cancer. (Id. at
11.)
The Examiner notes that the manner of administering the composition
is not specifically taught by Busch. (Final Action 6.) The Examiner turns to
Le and Juturu finding the claimed administration would have been obvious
to one of ordinary skill in the art. In particular, the Examiner finds that Le
2 Dr. Albert Busch, US 1,688,228, issued Oct. 16, 1928.
3 Juturu et al., US 2004/0097467 Al, published May 20, 2004.
4 Tien Cahn Le, WO 2006/136003 Al, published Dec. 28, 2006.
5 Choi et al., US 6,884,440 B2, issued Apr. 26, 2005.
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teaches monomeric or oligomeric silicic acid for internal uses and that it was
known that “orthosilicic acid and its derivatives in solution are relatively
stable until a concentration of about 1 mg/100 mL” but that “when the
concentration increases, the silicic acids have a tendency to make oligomers
and polymers (due to the siloxane bonds formation) and precipitate in
solution, which decrease the bioavailability or biodisponibility (paragraph
92).” {Id. at 4—5.) The Examiner further finds that Le teaches “the addition
of stabilizers has been found to prevent or reduce this polymerization
phenomenon and allows preserving the assimilable monomeric shape of
these acids (paragraph 92).” {Id. at 5.) Additionally, the Examiner finds that
Le teaches the compounds may be formulated for parenteral administration
including by injection or continuous infusion. (Id. )
The Examiner finds that Juturu teaches administering an arginine-
silicate-inositol complex “parenterally, orally, intravenously or topically by
solid, liquid or both” that may be used to treat conditions including cancer.
{Id. at 5.) The Examiner finds that the silicate used to make the complex
may be a silicate salt such as sodium silicate. {Id.) In light of the foregoing,
the Examiner concludes it would have been obvious to have selected a
known suitable administration method for the known administration of
silicate for treating cancer taught in Busch since such would have been
“within the purview of ordinary skill in the art in the absence of evidence to
the contrary.” {Id. at 6.)
The Examiner notes that Busch does not explicitly teach the cancers
claimed or the concentration of the active agent claimed. (Final Action 5.)
The Examiner contends that “these deficiencies are cured by Choi.” {Id.)
According to the Examiner, Choi teaches sodium metasilicate in the
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preparation BARADON shows inhibitory activity against carcinoma of
human lung and osteogenic sarcoma of human. {Id. citing Example 9 of
Choi.) The Examiner calculates that the amount of sodium metasilicate used
in the example demonstrating inhibitory activity against these cancers
“would correspond to a range of 0.067 mg/ml and 1 mg/ml.” {Id. at 6.)
According to the Examiner, these concentrations “overlap with or are close
to the instantly claimed invention.” {Id. at 7.) The Examiner concludes that
it would have been obvious to use a suitable concentration of silicate such as
taught in Choi in order to effectively treat cancer, and it would amount to
routine optimization to arrive at an optimum dosage within the concentration
range claimed. {Id. at 6—7.)
Claim 1
As to claim 1, Appellants argue that there is insufficient evidence to
establish that the composition of Busch necessarily must release orthosilicic
acid (Si(OH)4) in vivo as claimed. Appellants rely on the Kinrade
Declaration6 to support their contention that the Busch composition would
not be understood by one of ordinary skill in the art to expressly or
inherently disclose the claimed orthosilicic acid species. (Appeal Br. 5—7.)
Professor Kinrade asserts that Busch’s compositions “are equivalent
to those used as water/fire-resistant glues and paints, [that] are known to be
dispersions of globular casein proteins with electrostatically adsorbed
particles of high molecular weight polysilicic acid.” (Kinrade Deck 111.)
6 Declaration of Professor Stephen D. Kinrade filed June 26, 2015.
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Application 12/250,624
However, the Chemical Catalog cited7 in support of the foregoing statement
is merely a subject index that lists “wood, adhesives for,” various purposes
and does not indicate anything specific about a silicate composition. And
the remaining literature articles cited8 concern investigations of beta-casein
on silicon oxide surfaces (a silicon wafer with an oxide layer), or a silicon
block, not the combination of metasilicate of sodium combined with casein
or other albuminate of animal or vegetable origin. None of these references
can be said to demonstrate that the Busch composition forms a protein
dispersion with adsorbed high molecular weight polysilicic acid.
Professor Kinrade further contends that the composition of Le is a
formulation “analogous to those of Busch” because it “appears to be
describing the extraction of inorgranic, polymeric silicic acids from plants . .
. which are dissolved in caustic (pH >10) and reacted with a protein.”
(Kinrade Decl. 115.) However, the fact that Le may be describing
something similar to Busch does not establish that Busch’s composition is a
polymeric silicic acid. Moreover, as the Examiner pointed out Le teaches
specifically that it was known that “stabilizers prevent or reduce”
polymerization that is known to occur with orthosilicic acid “preserving the
assimilable monomeric shape.” (Lei 92.) While Professor Kinrade does
7 Vail, J. G., Soluble Silicates in Industry. American Chemical Society
Monograph Series. The Chemical Catalog Company: New York, 1928, p.
443.
8 F. Tiberg et al., Beta-casein adsorption at the silicon oxide-aqueous
solution interface, 2 Biomacromolecules, 844—50 (2001); D. Follows et al.,
Beta-casein adsorption at the silicon oxide-aqueous solution interface:
calcium ion effects, 5 Biomacromolecules, 319—25 (2004); O. Svensson, et
al. Adsorption of f-casein to hydrophilic silica surfaces. Effect of pH and
electrolyte, 36 Food Hydrocolloids 332—338 (2014).
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Application 12/250,624
not believe that Le is using such stabiliziers (Kinrade Decl. 16—17), he
does not disagree with the statement in Le that such was known in the prior
art. Appellants do not provide sufficient evidence that establishes such
stabilization so as to prevent polymerization is not the function of the casein
in Busch’s composition that includes sodium metasilicate that when
dissolved in hot water forms a composition of neutral pH and is easily
absorbed by the mucous membrane. (Busch 2:10-16, and claims 5 and 6.)
We have “broad discretion as to the weight to give to declarations
offered in the course of prosecution.” In re American Acad, of Science Tech
Ctr., 367 F.3d 1359, 1368 (Fed. Cir. 2004). Where the factual support for
expert opinion is lacking, the opinion testimony has little probative value.
See Ashland Oil, Inc. v. Delta Resins & Refractories, Inc., 776 F.2d 281, 294
(Fed. Cir. 1985) (“Lack of factual support for expert opinion going to factual
determinations, however, may render the testimony of little probative value
in a validity determination.”) In light of the foregoing, we do not find
Appellants have provided sufficient evidence to rebut the Examiner’s
finding that Busch’s casein sodium metasilicate combination would
inherently result in the liberation of orthosilicic acid in vivo if provided to a
patient for silicic acid therapy for carcinoma.
Moreover, we do not find Appellants have provided sufficient
evidence to rebut the Examiner’s finding that Busch’s teaching that it was
known in the prior art to provide, in small doses in silicic acid therapy for
carcinoma, sodium metasilicate that inherently results in liberation of
orthosilicic acid in vivo. (Appeal Br. 5.) As the Examiner noted, the
compound that Busch teaches was used and was determined to reach the
tissue of the lungs and deposit silicic acid is the same compound described
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in Appellants’ Specification for delivery to treat carcinoma (Spec. 21—22
(Melanoma Model and Sarcoma Model), Spec. 23 (describing making a
sodium silicate solution)), i.e., Na2Si03. (Ans. 3—4.) Appellants again rely
on the Declaration of Professor Kinrade as rebuttal evidence. (Appeal Br.
5.) Professor Kinrade contends that the term silicic acid as used in Busch
would have been understood at the time of Busch and now to mean a
polymeric silicon dioxide, not the monomeric species of Si(OH)4 required by
the claims. (Kinrade Decl. |7.) We are not persuaded that the dictionaries
relied upon by Professor Kinrade would result in one of ordinary skill in the
art concluding that the silicic acid therapy referred to in Busch was the
deposition of a polymeric silicon dioxide. That is because Busch teaches
that sodium metasilicate “has been proved experimentally. . . that it. . . is
resorbed and assimilated by all organs of the human body, while a part of it
is excreted” and that in silicic acid therapy the silicic acid is what is
deposited in the lungs. (Busch 1:10-47.) And Le teaches that it was known
that “[f]or internal uses, the soluble form of monomeric or oligomeric silicic
acid is necessary to preserve its assimilability” (Le Abs.) and that
orthosilicic acid is “relatively stable until a concentraton of about 1 mg/100
mL . . . [but] when the concentration increases, the silicic acids have a
tendency to make oligomers and polymers (due to the siloxane bonds
formation)” (Le 192). In short, it would appear that authors used the term
“silicic acid” alone to refer to monomeric silicic acid when the context of the
article concerned internal therapeutic use in a patient.
Nevertheless, we disagree with the Examiner’s factual finding that
Choi teaches a range of silicic acid for treating cancer that overlaps with the
claimed range so as to render the claimed concentration range of active to be
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Application 12/250,624
present in the solution of an active agent administered to a subject in need of
treatment for a cancer obvious. Professor Kinrade explains that Example 9
relied upon by the Examiner provides a concentration of at most 0.38—0.58
mg/ml of silicate, assuming that all of the silicate in solution is present in the
form of sodium silicate, not the 0.67 mg/ml to 1 mg/ml range calculated by
the Examiner. (Kinrade Decl. 122.) Professor Kinrade explained that the
Examiner’s calculations did not take into account that the BARODON®-4
composition is prepared with sodium metasilicate “pentahydrate.” (Id. )
According to Professor Kinrade “the calculated concentration of silicate in
the solution described in Example 9 of Choi is at most about half that of the
minimum value of the claimed concentration range of about 1—5 mg/mL.”
(Id.) The Examiner does not respond to the foregoing and, instead, simply
repeats his calculation. (Ans. 9.) Declaratory evidence as to an issue of fact
is entitled to substantial weight. In re Alton, 76 F.3d 1168, 1173—74 (Fed.
Cir. 1996). Summary dismissal of it was error. Id. at 1174.
We find Appellants’ evidence regarding the concentration of silicate
in Example 9 of Choi persuasive to establish that the concentration range
does not overlap with the claimed range, and instead, is at most about half of
the minimum concentration claimed. Moreover, we note as the Examiner
did (Final Action 4), that Le teaches that “[i]t has been observed that the
orthosilicic acid and its derivatives in solution are relatively stable until a
concentration of about 1 mg/100 mL.” This stable concentration is far less
than the range recited in the claims or discussed in Choi. Furthermore,
Busch indicates that “small doses [of sodium metasilicate] ... are necessary
for medication.” The Examiner has not provided any suggestion in the prior
art of the desirability of almost doubling the active agent beyond that taught
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by Choi. In light of the foregoing, we disagree with the Examiner’s
conclusion that the concentration range claimed would have been arrived at
by routine optimization. We, instead, are in agreement with Appellants that
the Examiner has failed to establish a prima facie case of obviousness on this
record with respect to the cited concentration range of the active agent.
Claim 36
In contrast to claim 1, claim 36 does not have a concentration
requirement. Independent claim 36 recites a method that comprises
“administering ... a composition . . . prepared by a method consisting
essentially of forming an aqueous solution of an active agent consisting of
an orthosilicic acid salt and adjusting the pH of said solution to about 6.0—
8.0.” The Examiner contends that Appellants have not provided a “clear
indication in the specification or claims of what the basic and novel
characteristics” of the invention are and so the Examiner has construed the
term “consisting essentially of’ as “comprising.” (Final Action 3—4.) The
Examiner further contends that the “consisting of’ language of the claim
concerns the active agent only while the composition is prepared by a
method which the Examiner has deemed to be open language and thus “the
albuminoid [of Busch] is not precluded from the instantly claimed
invention” because the “active of Busch ... is the silicate.” (Id. at 4.)
While we agree with the Examiner’s construction of claim 36
concerning treating “consisting essentially of’ as comprising and that the
active must be an orthosilicic acid salt, we nevertheless find that the
Examiner has failed to make out a prima facie case of obviousness. As
Appellants point out (Appeal Br. 7), Busch does not teach administration of
its complex for treating anything, much less cancer. While it is true, as the
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Examiner points out (Final Action 3), that Busch describes that the sodium
metasilicate and casein combination forms a white powder that when
dissolved in hot water has a neutral reaction on litmus paper (Busch 2:10—
16), such is not a description of the composition that is administered to the
subject in need of treatment.
Busch does teach that silicic acid therapy for cancer was known in the
art (Busch 1:10—17) and describes that it was known to administer sodium
metasilicate dissolved in soda water “for practical use” “to produce
bicarbonate of sodium from free alkali” (Busch 1:35—38). Soda water is
known to be an alkaline composition, but there is nothing in Busch to
indicate that the pH of the dissolved formulation was adjusted to be between
6 and 8 to achieve the composition in solution that was administered to the
patient.
We note that, regarding the obviousness of the concentration of the
silicate active agent recited in claim 1, the Examiner cites to Choi’s teaching
of a BARODON preparation, a composition that is made by dissolving
sodium metasilicate pentahydrate and borax, among other things, in water
that exhibited inhibitory activity against four types of cancer. (Final Action
5.) That preparation has a pH of 13. (Id.; Choi 4:43—50, 5 (Preparation
Example 1 and Preparation Example 4).) Thus, the preparation of Choi is a
strongly alkaline solution. (Choi 6:46—54 (describing the preparation of
BARODON®-4), 15: 36-42 (describing that “BARODON®-4 was tested
for inhibitory activity against human tumor (cancer) cells of four kinds.”).)
Consequently, Choi does not provide a motivation to adjust the pH of
Busch’s disclosed silicic acid therapy composition to a solution having a pH
of between 6—8.
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The Examiner also cites Le for teaching monomeric or oligomeric
silicic acids for internal uses that may be formulated for parenteral
administration. (Final Action 4—5.) However, Le teaches preparations of
soluble organic silicic acid solutions in which the pH is very acidic, i.e.,
between 3.2 and 4.8. (Le 1127.) Consequently, Le also does not provide a
motivation to adjust the pH of Busch’s disclosed silicic acid therapy
composition to a solution having a pH of between 6—8.
In light of the foregoing, we conclude that the Examiner has failed to
establish a prima facie case of obviousness on this record with respect to the
pH range recited in claim 36.
SUMMARY
We reverse the rejection of Claims 1, 5, 26, 27, and 29-44 under 35
U.S.C. § 103(a) as unpatentable over Busch, Juturu, Le, and Choi.
TIME PERIOD FOR RESPONSE
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a).
REVERSED
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