Ex Parte Newton et al

Patent Trial and Appeal Board

Aug 7, 2018

12670834 (P.T.A.B. Aug. 7, 2018)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
12/670,834 01/26/2010
4743 7590 08/09/2018
MARSHALL, GERSTEIN & BORUN LLP
233 SOUTH WACKER DRIVE
6300 WILLIS TOWER
CHICAGO, IL 60606-6357
FIRST NAMED INVENTOR
Maurice Sydney Newton
UNITED STATES DEPARTMENT OF COMMERCE
United States Patent and Trademark Office
Address: COMMISSIONER FOR PATENTS
P.O. Box 1450
Alexandria, Virginia 22313-1450
www .uspto.gov
ATTORNEY DOCKET NO. CONFIRMATION NO.
3113 8/40004 5278
EXAMINER
GREENE, NAN A
ART UNIT PAPER NUMBER
1619
NOTIFICATION DATE DELIVERY MODE
08/09/2018 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):
mgbdocket@marshallip.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte MAURICE SYDNEY NEWTON,
JAMES DAVID MORRISON, RUTH DIANE PENNELL,
NIGEL PETER PHODES, and ALEXIS JOHN TOFT
Appeal2017-007180
Application 12/670,834
Technology Center 1600
Before JEFFREY N. FREDMAN, RYAN H. FLAX, and
TIMOTHY G. MAJORS, Administrative Patent Judges.
FREDMAN, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal 1 under 35 U.S.C. § 134 involving claims to a method
of treating a disease characterized by elevated levels of stomach acid in a
subject. The Examiner rejected the claims as obvious under 35 U.S.C.
103(a) and on the grounds of nonstatutory double patenting. We have
jurisdiction under 35 U.S.C. § 6(b). We reverse.
Statement of the Case
Background
"The present invention relates to the use of ... compounds as ...
antacid[ s ]" and the "use of such compounds for the treatment of conditions
1 Appellants identify the Real Party in Interest as OPKO Ireland Global
Holdings, Ltd., (see App. Br. 2).
Appeal2017-007180
Application 12/670,834
or diseases associated with adverse stomach acid levels" (Spec. 1:5-7). "It
is desirable that a compound used in the treatment of gastric ulcer should not
only be an effective acid buffering agent, but should also avoid sudden
changes in gastric pH" (Spec. 2:2--4). Antacids "may cause an 'acid
rebound effect"' and the claimed compounds "buffer to the optimum pH
range of between pH 3-4.5" and "avoid acid-rebound effect" (Spec. 2:8,
39:4--5).
The Claims
Claims 1, 3-15, 17, 23--42, 44--46, and 49 are on appeal. Claim 1 is
representative and reads as follows:
1. A method of treating a disease characterized by elevated
levels of stomach acid in a subject, comprising administering a
therapeutically effective amount of a mixed metal compound to
said subject, wherein the mixed metal compound comprises:
at least one trivalent metal selected from the group
consisting of iron (III) and aluminum; and
at least one divalent metal selected from the group
consisting of magnesium, iron, zinc, calcium, lanthanum, and
cenum,
wherein
(A) the mixed metal compound is of formula (I):
MII1-aMIIIaObAn-c.ZH20 (I)
where Mn is the at least one divalent metal;
Mm is the at least one trivalent metal;
An- is at least one n-valent anion;
2+a = 2b+Lcn;
Lcn < 0.9a; and
2
Appeal2017-007180
Application 12/670,834
z is 2 or less.
The Rejections
A. The Examiner rejected claims 1, 3-15, 35-39, 41, 42, and 44--
46 under 35 U.S.C. § I03(a) as obvious over Newton,2 Narita, 3 and
Hollander4 and optionally in view of Bejoy5 and/or Kostura6 (Ans. 2).
B. The Examiner rejected claims 17, 23-34, 40, and 49 under 35
U.S.C. § I03(a) as obvious over Newton, Narita, Hollander, Olmstead7, and
Bando8, and optionally in view of Bejoy and/or Kostura, as evidenced by
Hibino9, Hudson 1°, and Ansel 11 (Ans. 2-3).
C. The Examiner provisionally rejected claims 1, 3-15, 17, 23--42,
44--46, and 49 on the grounds of nonstatutory obviousness type double
2 Newton et al., WO 2006/085079 A2, published August 17, 2006.
3 Narita et al., JP-A-HI0-101569, published April 21, 1998.
4 Hollander et al., Antacids vs. Placebos in Peptic Ulcer Therapy: A
Controlled Double-Blind Investigation, 226(10) JAMA, 1181-85 (1973).
5 N. Bejoy, Hydrotalcite: The Clay that Cures, 6(2) RESONANCE, 57---61 (2001).
6 Kostura et al., Rehydration of Calcined Mg-Al Hydrotalcite in Acidified Chloride-
Containing Aqueous Solution, 72(9) COLLECT. CZECH. CHEM. COMMUN., 1284--94
(2007).
7 Olmstead et al., US 2005/0266071 Al, published December 1, 2005.
8 Bando et al., WO 2007/074909 Al, published in Japanese on July 5, 2007. The
corresponding US application (US 2009/0175959 Al, published July 9, 2009) is
relied upon for citation purposes.
9 Hibino et al., Calcination and Rehydration Behavior of Mg-Fe-C03 Hydrotalcite-
like compounds, 19 J. MAT. SCI. LETTERS, 1403---05 (2000).
10 Hudson et al., Thermal Conversion of a Layered (Mg/Al) Double Hydroxide to
the Oxide, J. MATER. CHEM., 5(2), 323-29 (1995).
11 Ansel et al., PHARMACEUTICAL DOSAGE FORMS AND DRUG DELIVERY SYSTEMS,
1-243 (7th ed. 1999).
3
Appeal2017-007180
Application 12/670,834
patenting over claims 12 1, 3---6, 26-28, 32 and 34--37 of copending
Application No. 11/815,845 in view ofNarita, Hollander, Olmstead, and
Bando, and optionally in view of Bejoy, as evidenced by Hibino, Hudson,
and Ansel (Ans. 3--4).
D. The Examinerrejected 13 claims 1, 3-15, 17, 23--42, 44--46 and
49 on the grounds of nonstatutory obviousness type double patenting over
claims 1-18 of US 9,168,270 B2 in view of Newton, Narita, Hollander, and
Olmstead, and optionally in view of Bejoy, as evidenced by Hibino, Hudson,
and Ansel (Ans. 4).
E. The Examiner provisionally rejected claims 1, 3-15, 17, 23--42,
44--46 and 49 on the grounds of nonstatutory obviousness type double
patenting over claims 14 12-15, 18-21, and 23-25 of cop ending Application
No. 13/270,358 in view ofNarita, Hollander, Olmstead, and Bando, and
optionally in view of Bejoy, as evidenced by Hibino, Hudson, and Ansel
(Ans. 4--5).
A. Obviousness
Because all of the obviousness rejections tum on the same issue and
rely upon the basic combination of Newton, Narita, and Hollander and
optionally Bejoy and/or Kostura, we will consider them together.
12 Although the Examiner provisionally rejected the claims over claims 1, 3---6, 26-
30, 32, and 34--37 of copending Application No. 11/815,845, claims 29-30 are
currently cancelled.
13 Copending Application No. 12/162,914 issued as US 9,168,270 B2 on October
27, 2015. This rejection will be treated as a rejection over the patent.
14 Although the Examiner provisionally rejected the claims over claims 1-25 of
copending Application No. 13/270,358, claims 1-11, 16-17, and 22 are currently
cancelled.
4
Appeal2017-007180
Application 12/670,834
The Examiner finds that Newton teaches the claimed mixed metal
compound, but does not expressly teach that the compound is "useful as
antacid composition[]" or can be used to treat "peptide ulcers" (Final Act.
6).
The Examiner finds that Narita teaches "double layered hydroxides
having the divalent metal magnesium (Mg) and the trivalent metal iron (Fe)"
of the "starting material" (Final Act. 6). The Examiner finds that Narita
teaches that "double layered hydroxides" can be used as "antacids suitable
for the treatment of diseases associated with adverse stomach acid levels"
(Final Act. 6). The Examiner finds that Hollander teaches that "antacids are
the mainstay of current ( circa 1973) medical therapy for peptic ulcer
disease" (Final Act. 6). The Examiner finds that Bejoy teaches that
hydrotalcites ( doubled layered hydroxides) "are useful for the treatment of
peptic ulcer disease" (Final Act. 6-7).
The Examiner finds that it would be prima facie obvious to use the
compositions taught by Newton and Nari ta for the treatment of peptic ulcer
disease, because "the antacids are known to be efficacious for the treatment
of peptic ulcer disease" (Final Act. 7).
The issue with respect to this rejection is: Does the evidence of
record support the Examiner's conclusion that the combination of Newton,
Narita, and Hollander and optionally Bejoy and/or Kostura render the claims
obvious?
Findings of Fact
1. Newton teaches the claimed "mixed metal compound of
formula (I)" (Newton 5---6).
5
Appeal2017-007180
Application 12/670,834
2. Newton teaches that compounds of formula (I) can be used as a
medicine for "phosphate binding" and "preferably for the prophylaxis or
treatment ofhyperphosphataemia" (Newton 10).
3. Narita teaches using a "double hydroxide" compound of
formula (II) as an "antacid" (Narita ,r,r 1, 4--6).
4. Hollander teaches that antacid "administration has been the
mainstay of current medical therapy for peptic ulcer disease" (Hollander
1181 ).
5. Kostura teaches that hydrotalcite reconstitutes when placed in
solutions ofHCl and KCl for 150 hours. (Kostura 1286-88).
6. Bejoy teaches that hydrotalcite can be used to treat peptide
ulcers (Bejoy Abstract).
7. The Newton Declaration 15 states that a "person of ordinary skill
in the art would not have considered that a patient in need of a phosphate
binder [ would] ... also necessarily have elevated stomach acid levels and
also be in need of an antacid" (Newton Deel. ,r 9).
8. The Newton Declaration states that a person of ordinary skill in
the art would not have expected that a compound of formula (I) was
"suitable for use in treating a disease characterized by elevated levels of
stomach acid in a subject or for neutralizing or buffering stomach acid in a
subject, much less that such a compound could demonstrate increased
antacid properties as compared to a layered double hydroxide structure
compound" (Newton Deel. ,r 10).
15 Declaration of Dr. Maurice S. Newton, dated Aug. 19, 2013.
6
Appeal2017-007180
Application 12/670,834
9. The Newton Declaration states that one of ordinary skill in the
art "would not expect that rehydration to the original structure could be
achieved in vivo after oral administration," because typical conditions for
rehydration "would not be present in vivo during oral administration for use
of the claimed compounds" (Newton Deel. ,r,r 13-18).
10. The Newton Declaration states that even if rehydration occurred
in vivo, one would expect the return to a basic double-layered hydroxide
structure rather than the original structure. One would also expect changes
to the structure including incomplete rehydration resulting in the continued
presence of a mixed metal oxide, and changes in the anions incorporated into
the layered structures. One would not expect "a rehydrated product to
necessarily have antacid properties simply by virtue of the starting material
for the calcined product having antacid properties" (Newton Deel. ,r,r 19-
22).
Principle of Law
"In proceedings before the Patent and Trademark Office, the
Examiner bears the burden of establishing a prima face case of obviousness
based upon the prior art." In re Fritch, 972 F.2d 1260, 1265 (Fed. Cir.
1992).
Analysis
Appellants contend that there "is no teaching or suggestion in Newton
of any other use of the compound of formula (I), much less a suggestion to
use the compounds of formula (I) for treating a disease characterized by
elevated levels of stomach acid in a subject or for neutralizing or buffering
stomach acid in a subject" (App. Br. 4).
7
Appeal2017-007180
Application 12/670,834
The Examiner agrees that Newton does not teach that compounds of
Formula I are useful as antacids (Final Act. 6), but responds that
"administering to the stomach of a patient with elevated levels of stomach
acid the compounds of [Narita] would likely have been within the scope of
administering the compounds of formula (I)" (Ans. 7). The Examiner
further states that the compositions of Newton and Narita have "substantially
identical chemical structures" and therefore "have substantially identical
biochemical properties" (Ans. 7). Additionally, the Examiner states that
since "double layered hydroxides ... act as phosphate binders" and are
"useful for antacid compositions," one of ordinary skill in the art would have
reasonably predicted that the compounds of Formula I would have antacid
properties (Ans. 8).
Appellants respond that the "compounds of the claims and the
compounds of N arita represent distinct [compounds] and such distinctions
would have been recognized by the skilled person" (Reply Br. 2).
Moreover, Appellants respond, "[b ]ased on the distinctions in the chemical
structures, the expectation in the art was that the compounds would also
have distinct properties, including biochemical properties" (Reply Br. 3; Cf
App. Br. 9, 12).
Appellants' arguments are persuasive. Formula I (recited in claim 1
and Newton) and Formula II (recited in Narita) are structurally different (FF
1, 3, 7, 8). Moreover, the Examiner does not present any evidence disputing
the evidence provided by the Newton Declaration that the compound of
Formula I would not have been expected to have antacid properties (FF 8).
While the Examiner does provide evidence that compounds of Formula II
( double layered hydroxides) can be used as antacids or for treating peptide
8
Appeal2017-007180
Application 12/670,834
ulcers, the Examiner does not provide any evidence that compounds of
Formula I can treat stomach acid or peptic ulcers.
The presumption of obviousness based on a reference disclosing
structurally similar compounds may be overcome where there is evidence
showing there is no reasonable expectation of similar properties in
structurally similar compounds. In re May, 574 F.2d 1082, (CCPA 1978)
( appellant produced sufficient evidence to establish a substantial degree of
unpredictability in the pertinent art area, and thereby rebutted the
presumption that structurally similar compounds have similar properties).
Here, the Newton Declaration provides such evidence that the ordinary
artisan "would not expect that rehydration to the original structure [ for the
claimed compound] could be achieved in vivo after oral administration,"
because typical conditions for rehydration "would not be present in vivo
during oral administration for use of the claimed compounds" (FF 9).
The Examiner also finds that Newton teaches "reduction" when the
"bivalent metal magnesium is released by ... heat treatment" and that since
this process "does not result in the loss of the biochemical activity as a
phosphate binder," it "would not have resulted in the loss of the biochemical
property as an antacid" (Ans. 7).
Appellants respond that the Examiner "provides no support for this
statement" (Rep. Br. 3). Appellants further contend "[a]s taught in Newton,
the structural details of the starting material change[] based on the
calcination process taught in Newton, and, ... such changes affect the
properties of such compounds and their suitability for specific applications
(e.g., phosphate binders, antacids, catalyst, etc.)" (Reply Br. 3). Appellants
further contend that a person of ordinary skill in the art would not have
9
Appeal2017-007180
Application 12/670,834
"reasonably expected from the teachings of Newton of the maintenance of
phosphate binding properties that the disclosed compounds of Newton
would necessarily maintain other biochemical properties exhibited by the
starting material" (Reply Br. 3--4).
Appellants' arguments are persuasive. The Examiner has not
provided evidence supporting the finding that it would be reasonable to
expect maintenance of antacid properties based on maintained phosphate
binding properties, while Appellants have provided rebuttal evidence (FF 7-
8).
The Examiner further argues that the compound of Formula I will
rehydrate in the stomach, because Kostura teaches samples with "different
ratios of Mg/ Al" that correspond to the claimed compound "rehydrated in
aqueous solutions of various acidity with the initial HCl concentration of 0-
0. 8 mol/L" (Ans. 9).
We find the Examiner's rationale unpersuasive because, based on the
evidence provided by Newton, one of ordinary skill in the art would not
have been likely to predict that Formula I will rehydrate completely to form
Formula II (FF 9-10). Moreover, even assuming arguendo that the
compound of Formula I will rehydrate in the stomach, the Examiner's own
cited reference of Kostura demonstrates rehydration occurred after 150 hours
(FF 5). The Examiner provides no evidence that the compound of Formula I
would remain in the stomach for 150 hours or that such a lengthy delay for
rehydration would be functional for treating stomach acid in a patient.
To the extent that the Examiner relies upon a finding that
administering Formula I will inherently result in formation of Formula II
(Ans. 8-10), there is no evidence that it will rehydrate to a therapeutically
10
Appeal2017-007180
Application 12/670,834
effective amount as required by claim 1 for treating or buffering adverse
levels of stomach acid or peptic ulcer. "Inherency ... may not be
established by probabilities or possibilities. The mere fact that a certain
thing may result from a given set of circumstances is not sufficient."
MEHL/Biophile Int'l. Corp. v. Milgraum, 192 F.3d 1362, 1365 (Fed. Cir.
1999).
Moreover, even if Formula I inherently forms Formula II in vivo in a
suitable time frame for patient treatment and in an amount that is
therapeutically effective ( elements not evidenced here), there does not
appear to be a reason to administer Formula I to a patient who has adverse
levels of stomach acid. The compounds of Formula I were not known to be
useful for treating adverse levels of stomach acid or for buffering stomach
acid and the patient populations for administering phosphate binders and
antacids do not appear to overlap (FF 7-8). A prima facie case for
obviousness requires "a reason that would have prompted a person of
ordinary skill in the relevant field to combine the elements in the way the
claimed new invention does." KSR Int 'l Co. v. Teleflex Inc., 550 U.S. 398,
418 (2007).
Conclusion of Law
The evidence of record does not supports the Examiner's conclusion
that the combination of Newton, Narita, and Hollander and optionally Bejoy
and/or Kostura render the claims obvious.
B. Nonstatutory Obviousness Type Double Patenting
Copending Applications 11/815,845 and 13/270,358 correspond to
Newton, because copending Application No. 11/815,845 is the National
11
Appeal2017-007180
Application 12/670,834
Stage entry of Newton and copending Application No. 13/270,358 is a
divisional of copending Application No. 11/815,845. The double patenting
rejection of copending Application No. 12/162,914 relies on Newton.
All of the obviousness-type double patenting rejections tum on the
same issue as in the obviousness rejections, discussed above, and rely upon
the basic combination of Newton, Narita, Hollander, and Olmstead, and
optionally Bejoy. For the reasons specified above regarding the obviousness
rejections, we do not find that it would have been obvious to a person of
ordinary skill in the art to use the compounds recited in the copending claims
in combination with the other cited prior art to treat or buffer stomach acid
levels. We do not find that a person of ordinary skill in the art would have
had reason to administer these compounds to treat or buffer stomach acid.
SUMMARY
In summary, we reverse the rejection of claims 1, 3-15, 35-39, 41, 42,
and 44--46 under 35 U.S.C. § 103(a) as obvious over Newton, Narita, and
Hollander and optionally in view of Bejoy and/or Kostura.
We reverse the rejection of claims 17, 23-34, 40, and 49 under 35
U.S.C. § 103(a) as obvious over Newton, Narita, Hollander, Olmstead, and
Bando, and optionally in view ofBejoy and/or Kostura, as evidenced by
Hibino, Hudson, and Ansel.
We reverse the provisional rejection of claims 1, 3-15, 17, 23--42, 44--
46, and 49 on the grounds of nonstatutory obviousness type double patenting
over claims 1, 3---6, 26-28, 32, and 34--37 of copending Application No.
11/815,845 in view ofNarita, Hollander, Olmstead, and Bando, and
optionally in view of Bejoy, as evidenced by Hibino, Hudson, and Ansel.
12
Appeal2017-007180
Application 12/670,834
We reverse the rejection of claims 1, 3-15, 17, 23--42, 44--46, and 49
on the grounds of nonstatutory obviousness type double patenting over
claims 1-18 of US 9,168,270 B2 in view ofNewton, Narita, Hollander, and
Olmstead, and optionally in view of Bejoy, as evidenced by Hibino, Hudson,
and Ansel.
We reverse the provisional rejection of claims 1, 3-15, 1 7, 23--4 2, 44--
46, and 49 on the grounds of nonstatutory obviousness type double patenting
over claims 12-15, 18-21, and 23-25 of copending Application No.
13/270,358 in view ofNarita, Hollander, Olmstead, and Bando, and
optionally in view of Bejoy, as evidenced by Hibino, Hudson, and Ansel.
REVERSED
13