Maurice Sydney. Newton et al.

Patent Trials and Appeals Board

Dec 26, 2019

11815845 - (D) (P.T.A.B. Dec. 26, 2019)

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.
11/815,845 08/08/2007 Maurice Sydney Newton 31138/40001 2382
4743 7590 12/26/2019
MARSHALL, GERSTEIN & BORUN LLP
233 SOUTH WACKER DRIVE
6300 WILLIS TOWER
CHICAGO, IL 60606-6357
EXAMINER
GREENE, IVAN A
ART UNIT PAPER NUMBER
1619
NOTIFICATION DATE DELIVERY MODE
12/26/2019 ELECTRONIC
Please find below and/or attached an Office communication concerning this application or proceeding.
The time period for reply, if any, is set in the attached communication.
Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the
following e-mail address(es):
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,
NIGEL PETER RHODES, and ALEXIS JOHN TOFT
____________

Appeal 2018-004205
Application 11/815,845
Technology Center 1600
____________

Before RYAN H. FLAX, RACHEL H. TOWNSEND, and
CYNTHIA M. HARDMAN, Administrative Patent Judges.

FLAX, Administrative Patent Judge.

DECISION ON APPEAL
This is a decision on appeal under 35 U.S.C. § 134(a) involving
claims directed to a medicament for binding phosphate in an animal, a
pharmaceutical formulation, and a unit dosage form. Appellant appeals the
rejection of claims 1, 3, 5, 6, 26, 28, 32, 34, 35, and 37–42 under 35 U.S.C.
§§ 102(b) and 103(a). 1 We have jurisdiction under 35 U.S.C. § 6(b).
We reverse.

1 “Appellant” herein refers to the “applicant” as defined by 37 C.F.R.
§ 1.42. Appellant identifies “OPKO Ireland Global Holdings, Ltd.,” as the
real party in interest. Appeal Br. 3.
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RELATED MATTERS
Appellant states, “[a]n appeal is pending in U.S. Patent Application
No. 13,270,358, which is a divisional application of the present application.
The ’358 application is also owned by OPKO Ireland Global Holdings, Ltd.”
Appeal Br. 3. The aforementioned appeal was Appeal No. 2018-004161,
wherein the Board rendered a decision on June 20, 2019.
STATEMENT OF THE CASE
The Specification states, “[p]lasma phosphate levels may be reduced
by oral intake of inorganic and organic phosphate binders.” Spec. 1:14–15.
“Other aluminium compounds such as microcrystalline aluminium oxide
hydroxide (boehmite) and certain hydrotalcites have been proposed for this
use.” Id. at 1:20–22. Issues with aluminum toxicity and efficiency were
observed. Id. at 1–2. “To overcome the drawbacks associated with
aluminium and also problems of efficacy over a limited pH range,” the
Specification states, “WO-A-99/15189 [Roberts, see infra] discloses use of
mixed metal compounds which are free from aluminium and which have a
phosphate binding capacity of at least 30% by weight of the total weight of
phosphate present, over a pH range of from 2-8.” Id. at 2:13–17. The
Specification calls such materials “Layered Double Hydroxide” (also called
LDHs) or “hydrotalcite-like compounds” (also called HTlcs). Id. at 4.
Even these improved compounds presented drawbacks. As stated in
the Specification, “we have found that the mixed metal compounds of
WO-A-99/15189 release some of their divalent metal content in soluble
form during use.” Id. at 2:22–3:2. The Specification further states, “[w]e
have now found that the release of the divalent metal, e.g. magnesium,
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associated with the pharmaceutical use of compounds of WO-A-99/15189
can be significantly reduced by heat treatment.” Id. at 4:5–7.
Furthermore, the Specification describes that such heat treatment, also
called calcination, is a delicate procedure because “[e]xcessive calcination
also may lead to the formation of a Spinel crystalline structure, hence it is
preferred that the substances of the invention do not exhibit a Spinel
structure by x-ray diffraction.” Id. at 9:9–12. To address this spinel-
formation drawback, promote phosphate absorption, and limit magnesium
release, the Specification explains that, according to the invention, the heat
treatment is most preferably kept to a range of 250°C to 500°C, and the
duration is kept to no more than 3 hours. See id. at 7–9, 11, 13–14, 24–25,
29, 32, 37 (examples, method 1), 43 (Table 1), 55 (Table 4).
Claim 1 is representative and is reproduced below:
1. A substance for use as a medicament for binding
phosphate in an animal, comprising greater than 30% and up to
95% by weight of a phosphate binding, pharmaceutically
acceptable solid mixed metal compound of formula (I):
MII1-aMIIIaObAn-c.zH2O (I)
wherein MII is at least one bivalent metal;
MIII is Fe3+;
An- is at least one n-valent anion;
2+a = 2b+Σcn and Σcn < 0.9a, and
z is 2 or less;
wherein the compound of formula (I) is obtained by
heating a starting material comprising a layered double
hydroxide structure at a temperature in a range of 250 °C to 500
°C for 3 hours or less,
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wherein the substance is free of a Spinel structure as
determined by x-ray diffraction, and
upon administration, the compound releases into solution
at least 50% by weight less of the at least one bivalent metal as
compared to a release into solution of the at least one bivalent
metal from the starting material, and
wherein the starting material comprises a compound of
formula (II):
MII1-xMIIIx (OH)2An-y.mH2O (II)
wherein MII is at least one bivalent metal;
MIII is at least one trivalent metal;
An- is at least one n-valent anion;
x=Σny; and
O < x ≤ 0.5, 0 ≤ m ≤ 10.
Appeal Br. 21 (Claims Appendix) (formatting added). The Examiner has
identified that
[i]n the response to the Requirement for Restriction/Election
dated 12/31/2009 applicants have elected Group I drawn to
pharmaceutical compositions comprising a mixed metal
compound and have elected the mixed metal compound species
in which MII is magnesium; MIII is iron; a is 0.21; b is 1.08; c is
0.22; z is 0.15 and A is carbonate.
Non-Final Act. 2. Pursuant to this election and using the indicated values
for the recited variables, we understand the elected species covers
Mg0.79Fe0.21O1.08(CO32-)0.22·0.15H2O as formula (I), i.e., the post-heat-
treatment composition, and Mg0.79Fe0.21(OH)2(CO32-)0.14·1.85H2O, as
formula (II), i.e., the pre-heat-treatment starting material. We limit our
analysis to the elected species. See Ex parte Ohsaka, 2 USPQ2d 1460, 1461
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(BPAI 1987) (appropriate to limit discussion on ex parte appeal to elected
species).
Independent claim 26 is substantially the same as claim 1 except its
preamble recites “[a] pharmaceutical formulation comprising a phosphate
binding solid mixed metal,” and it recites that the formulation has “non-
chemically bound water” and “a solid pharmaceutically acceptable carrier.”
Appeal Br. 22 (Claims App’x.). Independent claim 38 is substantially the
same as claim 1, except its preamble states, “[a] unit dosage form
comprising greater than 30% by weight of a phosphate binding,
pharmaceutically acceptable solid mixed metal compound of formula (I)”
and, although reciting the same starting and resulting materials and the same
heat treatment as claim 1, does not expressly recite that the resultant
substance is “free of a Spinel structure.” Id. at 24.
The following rejections are appealed:
Claims 38 and 39 stand rejected under 35 U.S.C. § 102(b) as
anticipated by Hibino,2 as evidenced by Forano,3 and Fernández,4 or in the
alternative, under § 103(a) over this same prior art. Non-Final Act. 5–8.

2 T. Hibino et al., Calcination and rehydration behavior of Mg-Fe-CO3
hydrotalcite-like compounds, 19 J. MAT. SCI. LETT. 1403–05 (2000)
(“Hibino”).
3 Claude Forano, Environmental Remediation Involving Layered Double
Hydroxides, in CLAY SURFACES: FUNDAMENTALS AND APPLICATIONS, 426–
58 (F. Wypych & K.G. Satayanarayana eds., 2004) (“Forano”).
4 José Maria Fernández et al., The effect of iron on the crystalline phases
formed upon thermal decomposition of Mg-Al-Fe hydrotalcites, J. MATER.
CHEM. 2507–14 (1998) (“Fernández”).
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Claims 1, 3, 5, 6, 26, 28, 32, 34, 35, and 37–42 stand rejected under
35 U.S.C. § 103(a) over Hibino, Zhu,5 Forano, Châtelet,6 Roberts,7 Miyata,8
and Ansel.9 Non-Final Act. 8–20.
DISCUSSION
“[T]he examiner bears the initial burden, on review of the prior art or
on any other ground, of presenting a prima facie case of unpatentability. If
that burden is met, the burden of coming forward with evidence or argument
shifts to the applicant.” In re Oetiker, 977 F.2d 1443, 1445 (Fed. Cir. 1992).
I. ANTICIPATION
“Anticipation requires that all of the claim elements and their
limitations are shown in a single prior art reference.” In re Skvorecz, 580
F.3d 1262, 1266 (Fed. Cir. 2009). To anticipate “it is not enough that the
prior art reference discloses part of the claimed invention, which an ordinary
artisan might supplement to make the whole, or that it includes multiple,
distinct teachings that the artisan might somehow combine to achieve the
claimed invention.” Net MoneyIN, Inc. v. VeriSign, Inc., 545 F.3d 1359,
1371 (Fed. Cir. 2008); see also Microsoft Corp. v. Biscotti, Inc., 878 F.3d

5 H. Zhu et al., Different Mg to Fe Ratios in the Mixed Metal MgFe
Hydroxy-Carbonate Compounds and the Effect on Phosphate Binding
Compared With Established Phosphate Binders, 91 J. PHARMA. SCI. 53–66
(2001) (“Zhu”).
6 L. Châtelet et al., Competition between monovalent and divalent anions
for calcined and uncalcined hydrotalcite: anion exchange and adsorption
sites, 111 COLLOIDS & SURFACES A: PHYSIOCHEM. & ENGINEERING ASPECTS
167–75 (1996) (“Châtelet”).
7 WO 99/15189 (published Apr. 1, 1999) (“Roberts”).
8 US 4,629,626 (issued Dec. 16, 1986) (“Miyata”).
9 HOWARD C. ANSEL ET AL., PHARMACEUTICAL DOSAGE FORMS AND DRUG
DELIVERY SYSTEMS (Donna Balado ed., 7th ed. 1999) (“Ansel”).
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1052, 1068 (Fed. Cir. 2017) (“In order to anticipate the claimed invention, a
prior art reference must ‘disclose all elements of the claim within the four
corners of the document,’ and it must ‘disclose those elements ‘arranged as
in the claim.’”).
With these standards of law in mind, we analyze the Examiner’s
rejection and Appellant’s arguments regarding anticipation below.
The Examiner determined that independent claim 38 and dependent
claim 39, which depends therefrom, are anticipated by Hibino because the
reference discloses a mixed metal compound (a hydrotalcite-like compound,
or HTlc) having Mg and Fe in a 4:1 ratio, as well as the calcination of such a
material at temperatures of 400°C, 450°C, and 500°C. Non-Final Act. 5.
The Examiner took the position that the product disclosed by Hibino is
“structurally identical or substantially identical to applicants [sic] elected
species because it includes the same ingredient amounts made by the same
method.” Id. Acknowledging that claim 38 recites “a unit dosage form,” the
Examiner determined that Hibino’s “examples were rehydrated in Na2CO3
aqueous solution,” and that this was an aqueous suspension and, therefore, a
unit dosage form. Id. at 6. The Examiner acknowledged that Hibino did not
express that its compositions were free of spinel or functioned to reduce
bivalent metal release into solution upon administration as compared to the
claimed starting material. Id.
Appellant argues that Hibino fails to disclose a unit dosage form
because such a form is not taught by mere rehydration, which may not result
in an aqueous solution containing greater than 30% by weight of the
calcined compound. Appeal Br. 7–8. Appellant argues that Hibino does not
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indicate a spinel-free structure, but indicated the presence of spinel. Id. at 7–
10 (Appellant’s Specification and other independent claims, as discussed
above, indicate the claimed material would be essentially free of spinel).
Appellant argues that Hibino does not actually disclose any calcination
durations and the reference’s mere citation to Fernández, which does
disclose 2 hour calcinations, is not sufficient for anticipation because it does
not indicate that such a duration was actually used in Hibino, particularly
because Fernández is directed to a different material (Mg-Al-Fe) than
Hibino (Mg-Fe). Reply Br. 2.
We find Appellant’s arguments persuasive and conclude that Hibino
does not anticipate the claims. Appellant is correct that Hibino does not
disclose the recited heating parameters. See, e.g., Hibino 1403–05; see also
Fernández 2507 (Abstract) (reference is directed to LDHs containing Mg,
FE, and Al, which is different from Hibino’s composition). Appellant’s
Specification explains that using the claimed heating parameters for the
claimed starting material results in a composition free of spinel, but Hibino
discloses finding spinel over the entire range of its heating temperatures and
suggests that the substance appears at even lower temperatures. See Hibino
1404–05. Hibino is silent as to providing its composition in a unit dosage
form, as claimed; it is only directed to an investigation into the properties of
the underlying composition. For at least these reasons, we reverse the
anticipation rejection.
II. OBVIOUSNESS
“The combination of familiar elements [or steps] according to known
methods is likely to be obvious when it does no more than yield predictable
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results.” KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007). “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). “Evidence that a compound is
unexpectedly superior in one of a spectrum of common properties [] can be
enough to rebut a prima facie case of obviousness.” In re Chupp, 816 F.2d
643, 646 (Fed. Cir. 1987) (evidence showed unexpectedly superior
properties of an herbicide when used on corn and soybeans, which overcame
a prima facie case of obviousness even though claims were not limited to use
on those plants).
With these standards of law in mind, we analyze the Examiner’s
rejection and Appellant’s arguments regarding obviousness below.
As noted above, the appealed (independent) claims are substantially
similar. The same findings of fact and arguments are presented for the
Board’s consideration and are determinative for both obviousness rejections.
Therefore, we address both rejections together.
The Examiner determined that independent claims 1, 26, and 38, and
all dependent claims, would have been obvious over the prior art
combination of Hibino, Zhu, Forano, Châtelet, Roberts, Miyata, and Ansel
(in the case of claims 38 and 39, the Examiner also cited Fernández, along
with Hibino and Forano). Non-Final Act. 5–20. The Examiner’s position is
that Zhu and Roberts each teach the usefulness of mixed metal compounds
as pharmaceutical anion (phosphate) absorbers, such as the starting material
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recited by each independent claim, which, when heat treated (calcinated), as
taught or suggested by other cited references, becomes the final compound
of the claims. The Examiner determined that Hibino, Châtelet, and Forano
(Fernández in the rejection specific to claims 38 and 39) teach or suggest
how to calcinate and the advantages of calcinating such materials, which
enhances their anion exchange capabilities, which relatedly enhances their
phosphate absorption. The Examiner determined that these references teach
or suggest the claimed temperature range for such calcination and suggest
the heating duration, e.g., Hibino teaches calcination at 400°C, 450°C, and
500°C, and Hibino references Fernández, which discloses calcinating at
450°C or 750°C for 2 hours. Finally, regarding the use of the compound in a
pharmaceutical composition, e.g., a medicament, a pharmaceutical
formulation, or a unit dosage form, the Examiner points to Miyata and Ansel
as teaching this.
We agree with the Examiner that it may be possible to arrive at the
claimed invention by piecing together the cited prior art. For example,
Roberts and Zhu teach the starting material and identify its usefulness
similarly to how the Specification describes it. But, while Hibino teaches
calcination of hydrotalcite-like compounds at temperatures falling within the
ranges claimed, it also discloses that its process causes spinel formation;
spinel formation is something that both the Examiner and Appellants agree
is undesirable in the claimed invention. See Hibino 1403–05. Châtelet may
teach increasing anionic exchange capacity of hydrotalcite compounds by
thermal treatment and the advantage of not exceeding 500–600°C, but it also
suggests that the thermal treatment should occur for 18 hours, which is 15
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hours longer than allowed by the appealed claims. See Châtelet 167–68.
Forano likewise teaches that calcinated hydrotalcite materials display higher
adsorption properties, such as for adsorbing phosphates, and describes a
range of temperatures between 200–500°C for calcination, where such
enhancement can occur before spinel formation, but Forano is not explicit
about heating duration. See Forano 430, 431, and 442. Fernández, a
reference cited by Hibino, and upon which the Examiner relies for the
presumed duration of Hibino’s heat treatment (see, e.g., Answer 15), teaches
thermal decomposition of hydrotalcites for a 2 hour duration at temperatures
of 450 ºC and 750 °C; however Fernández also indicates that thermal
decomposition in air at 450°C and also at 750°C leads to spinel formation.
See Fernández 2507, 2510, and 2513. Furthermore, as pointed out by
Appellant, Fernández is directed to a different material than Hibino.
Given the ambiguities of the prior art, we conclude the ordinary
skilled artisan would not have recognized the significance of and
relationships between the teachings of the cited prior art so as to achieve the
claimed subject matter without knowledge of the claimed invention.
Moreover, Appellant argues the Specification evidences that the claimed
invention produces the unexpected result of “a reduced release of bivalent
metal in solution, while improving phosphate binding capacity” (in addition
to lack of spinel formation). Appeal Br. 17–20, Table 1 (citing Spec. 4:5–
10, 43), 55 (Table 4) (citing Newton Declaration ¶¶ 20–25)). While the
skilled artisan may have expected the exemplified improvements in
phosphate binding capacity based on the disclosures of, e.g., Châtelet and
Forano, the Examiner has not cited persuasive support in the record that the
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exemplified reduction in MgII release would have also been expected. The
Specification describes that when starting materials (which the Specification
identifies as Batches A and B — see Spec. 37) were calcinated at the
claimed temperature and duration, reductions in MgII release were observed
compared to uncalcinated materials or materials calcinated outside the
claimed time/temperature ranges. Significantly, in view of the claimed 3-
hours-or-less claim limitation, the Specification’s Table 4 shows that 5
minute and 3 hour heat treatments at 500°C provided respective Mg releases
of, e.g., 0.15 and 0.1 mmol/L, while a heat treatment at the same
temperature, but for 16 hours resulted in an Mg release of 1.05 mmol/L, or
about 10 times greater. Uncalcinated material had an Mg release of, e.g., 5.9
mmol/L, or about 60 times greater.
The Newton Declaration, submitted by Appellant, states that such
results were significant and unexpected. See Newton Declaration ¶¶ 21–24.
The Newton Declaration states that “the inventive methods and compounds”
produced the discussed results and “a mixed metal compound as we claim
demonstrates a significant reduction in the release of the bivalent metal as
compared to the uncalcinated starting material,” and that the “unexpected
results” illustrated by the Specification’s Table 1 and Table 4 are “of our
invention.” See Newton Declaration ¶¶ 9, 21, 23, and 24. Appellant avers
“the demonstration of unexpected results is commensurate in scope with the
claims, particularly in view of the elected species.”10

10 We note, it appears the compounds identified in the Specification as
Batch A and Batch B (Spec. 37) are not identical to the starting material of
the claims. For example, the Specification’s Batches A and B include SO4
and Na2SO4 in the pre-calcinated starting material, but the formula (II)
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In view of the somewhat ambiguous teachings of the prior art cited
against the claims here and the prior art combination’s sometimes
conflicting teachings concerning relevant subject matter, we conclude that
the balance of evidence on appeal favors Appellant’s position. There is a
lack of definitive evidence that the cited prior art would have been modified
to utilize the claimed heat treatment parameters for the claimed starting
material to produce the claimed final composition, which is used as, e.g., a
pharmaceutical. Furthermore, the evidence of unexpected results appears to
be sufficient when considered alongside the evidence of obviousness to
outweigh any case for obviousness, if indeed a prima facie case was made in
the first instance. In view of the above, we conclude the balance of evidence
supports Appellant and we reverse the Examiner’s rejections for
obviousness.
CONCLUSION
The anticipation rejection of claims 38 and 39 is reversed.
The obviousness rejection of claims 38 and 39 is reversed.
The obviousness rejection of claims 1, 3, 5, 6, 26, 28, 32, 34, 35, and
37–42 is reversed.

starting material of the claims does not. Further, the amounts of H2O are not
the same when comparing Batches A and B to the elected species. However,
the significance of such differences is not apparent and the Examiner does
not contend that Appellant’s evidence of unexpected results is not
commensurate in scope with the claims.
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In summary:
Claims
Rejected
35 U.S.C. § Reference(s)/Basis Affirmed Reversed
38, 39 102(b) Hibino 38, 39
38, 39 103(a) Hibino, Forano, Fernández 38, 39
1, 3, 5, 6,
26, 28, 32,
34, 35, 37–
42
103(a) Hibino, Zhu,
Forano, Châtelet,
Roberts, Miyata,
and Ansel

1, 3, 5, 6, 26,
28, 32, 34,
35, 37–42
Overall
Outcome

1, 3, 5, 6, 26,
28, 32, 34,
35, 37–42

REVERSED