Ex Parte Golomb et al

Patent Trial and Appeal Board

Nov 30, 2016

11296153 (P.T.A.B. Nov. 30, 2016)

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.
11/296,153 12/06/2005 Gershon Golomb 92114.003US4 1175
75004 7590 12/02/2016
CADWALADER, WICKERSHAM & TAFT LLP
ONE WORLD FINANCIAL CENTER
NEW YORK, NY 10281
EXAMINER
FRAZIER, BARBARA S
ART UNIT PAPER NUMBER
1611
NOTIFICATION DATE DELIVERY MODE
12/02/2016 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):
DOROTHY. AUTH @ CWT.COM
DOCKETING@CWT.COM
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PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte GERSHON GOLOMB and HAIM DANENBERG
Appeal 2015-006625
Application 11/296,1531
Technology Center 1600
Before RICHARD M. LEBOVITZ, JOHN G. NEW, and TIMOTHY G.
MAJORS, Administrative Patent Judges.
LEBOVITZ, Administrative Patent Judge.
DECISION ON APPEAL
This appeal involves claims directed to pharmaceutical compositions
comprising a bisphosphonate for intravenous administration. The
compositions are useful for treatment or prevention of restenosis. The
Examiner rejected the claims under 35 U.S.C. § 103(a). We have
jurisdiction under 35 U.S.C. § 134(a). The Examiner’s decision is reversed.
New grounds of rejection are set forth pursuant 37 C.F.R. § 41.50(b).
1 The real party in interest listed in the Appeal Brief is BlOrest Ltd.
Appeal 2015-006625
Application 11/296,153
STATEMENT OF THE CASE
Claims 1,3,4, 6, 15, 22, and 24—26 stand finally rejected by the
Examiner under 35 U.S.C. § 103(a) as obvious in view of DE ’890 (DE 196
37 890 Al, publ. Mar. 19, 1998), and Monkkonen (1994) (“The effects of
liposome surface charge and size on the intracellular delivery of clodronate
and gallium in vitro,” International Journal of Pharmaceutics, 107: 189—
197). Ans. 2.
Claim 1 is representative and reads as follows (see Appeal Br. 22 for
the complete structural formula of the bisphosphonate):
1. A pharmaceutical composition for intravenous
administration useful for treatment or prevention of restenosis
comprising a bisphosphonate having a formula:
[FORMULA OMITTED]
in an aqueous liposome dispersion and having a size of
0.15 to 300 nanometers, wherein the liposome dispersion
comprises distearoyl phosphatidylcholine (DSPC), distearoyl-
phosphatidylglycerol (DSPG), and cholesterol in a molar ratio
of 3:1:2;
wherein said composition contains an effective amount of
said bisphosphonate for the treatment or prevention of
restenosis.
REJECTION
Claims 1,3,4, 6, 15, 22, and 24—26 stand rejected by the Examiner as
obvious in view of DE ’890 and Monkkonen (1994). The Examiner found it
obvious to have modified the teachings in DE ’980 with the teachings in
Monkkonen (1994). Ans. 2—A.
We reverse the rejection. Claim 1 is directed to a liposome dispersion
comprising “an effective amount of said bisphosphonate for the treatment or
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Application 11/296,153
prevention of restenosis.” DE ’890 describes a liposome composition
comprising clodronate as useful to prevent kidney rejection. DE ’890, p. 2.
Monkkonen (1994) teaches liposomes comprising clodronate as useful in
inflammatory disease. Monkkonen, Abstract. The Examiner did not provide
adequate evidence that the composition in DE ’890 comprises “an effective
amount of said bisphosphonate for the treatment or prevention of restenosis”
as required by all the rejected claims. See Ans. 5. The Examiner also did
not provide sufficient reason to use the amounts of clodronate described in
Monkkonen in DE ’890, which administers a liposome for a different
purpose than disclosed by Monkkonen.
NEW GROUNDS OF REJECTION
New grounds of rejection pursuant to 37 C.F.R. § 41.50(b) are set
forth below.
1. Claims 1, 3, and 6 are rejected under 35 U.S.C. § 102(b) (pre-AIA)
as anticipated by, or alternatively, under 35 U.S.C. § 103(a) (pre-AIA) as
obvious in view of, Monkkonen (1994). Medford (U.S. Pat. No. 5,380,747,
patented Jan. 10, 1995) is cited as evidence.
2. Claims 4, 15, 22, and 24—26 are rejected under 35 U.S.C. § 103(a)
(pre-AIA) as obvious in view of Monkkonen (1994), Rogers
(“Bisphosphonates Induces Apoptosis in Mouse Macrophage-like Cells In
Vitro by a Nitric Oxide-Independent Mechanism,” Journal of Bone and
Mineral Research, 11(10): 1482—1491, 1996), and Medford.
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Application 11/296,153
1. ANTICIPATION BY MONKKONEN
Findings of Fact
The following findings of fact (“FF”) are pertinent to the
determination that Monkkonen anticipates claims 1,3, and 6.
Specification of Application 11/296,153 involved in this appeal
FF 1. The Specification discloses that the claimed bisphosphonate
“affects restenosis by inhibiting phagocytic cells involved in the restenotic
cascade, such as macrophages/monocytes and fibroblasts.” Spec. 3:6—9.
FF2. The Specification also discloses:
In a further embodiment, the present invention includes a
method of treating or preventing restenosis by administering to
an individual, an effective amount of any compound or
composite known to inactivate or inhibit blood monocytes and
tissue macrophages, thereby treating or preventing restenosis.
Id. at 3:16—19.
Monkkonen
FF3. Monkkonen describes a liposome comprising clodronate.
Monkkonen, Abstract, 192 (Table 1).
FF4. Monkkonen teaches liposomes prepared from a 200 mM stock
solution, and, phospholipid and cholesterol in a proportion of 67:33 or about
2:1. Id. at 190 (“2.2 Preparation of liposomes”). The liposomes comprising
the phospholipid/cholesterol in the 2:1 ratio are described by Monkkonen as
having different proportions of DSPC and DSPG, including in a ratio of
75:25 (3:1) of DSPC to DSPG (Fig. 1 (unfilled triangles)).
FF5. A liposome having the amounts of DSPC/DSPG/cholesterol
described in FF4 is equivalent to a molar ratio of 3:1:2. Final Rej. 5.
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Application 11/296,153
FF6. Monkkonen teaches that the liposome comprising the clodronate
(FF3—FF5) are macrophage suppressive agents that may be useful in the
treatment of inflammatory diseases. Id. at 190 (col. 1, first full paragraph).
FF7. Monkkonen teaches that the size of its liposomes having 75:25
of DSPC to DSPG is 190 nanometers. Id. at 192 (Table 1).
Medford
FF8. Medford teaches, inter alia, that an inflammatory response leads
to clinically significant restenosis. Medford, col. 4,11. 45^49.
Discussion
Claim 1 is directed to a pharmaceutical composition for intravenous
administration comprising a bisphosphonate of a specifically recited formula
in an aqueous liposome dispersion. The liposome dispersion comprises (1)
DSPC, DSPG, and cholesterol in a molar ratio of 3:1:2. The composition
also comprises (2) an effective amount of the bisphosphonate for the
treatment of restenosis. Claim 6, which depends from claim 1, recites that
the (3) “bisphosphonate is clodronate, etidronate, tiludronate, pamidronate or
alendronate.” The liposomes have (4) a size of 0.15 to 300 nanometers.
Monkkonen describes a liposome with the same molar ratio of (1)
DSPC, DSPG, and cholesterol as claimed (FF4, FF5), where (3) the
bisphosphonate is clodronate (FF3, FF6).
Monkkonen teaches that its liposomes comprising clodronate are
macrophage suppressive agents (FF6). Monkkonen also teaches that its
liposomes comprising clodronate may be useful to treat inflammatory
disease (FF6). Consequently, Monkkonen’s liposomes comprise an
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effective amount of clodronate to suppress macrophages and treat
inflammation. Monkkonen, however, does not expressly teach that its
liposomes comprise (2) an effective amount of the bisphosphonate for the
treatment of restenosis as required by claim 1.
When the limitations of a claim are not expressly described in the
prior art, the PTO must show “sound basis for believing” that despite the
failure of the prior art to describe them, the limitations are inherently present
and “the products of the applicant and the prior art are the same.” In re
Spada, 911 F.2d 705, 708 (Fed. Cir. 1990). We find that a person of
ordinary skill in the art would realize that Monkkonen’s liposome
preparation comprising clodronate would be effective to treat or prevent
restenosis because the Specification discloses that the efficacy of the
bisphosphonates in treating restenosis is associated with macrophage
inhibition or inactivation (FF1, FF2), the same mechanism described by
Monkkonen for its liposomes (FF6). Because the mechanisms are the same,
the skilled worker would have reasonably expected that Monkkonen’s
liposome preparation would contain an effective amount of clodronate to
treat or prevent restenosis.
Furthermore, restenosis is an inflammatory response (FF8), and
Monkkonen teaches that its liposomes comprising clodronate are useful for
treating inflammatory disease (FF6), providing further basis to believe that
Monkkonen’s liposomes contain an effective amount of the bisphosphonate
to treat restenosis.
Monkkonen describes that its liposomes are 190 nm (FF7) which falls
within the recited range of liposomes having (4) a size of 0.15 to 300
nanometers.
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With respect to claim 3, which depends from claim 1, and further
comprises a diluent, Monkkonen teaches that the clodronate is prepared as a
200 mM stock solution (FF4) which would necessarily require a diluent to
make a solution.
Even if the amount of clodronate in Monkkonen’s liposomes is not
anticipatory, it would have been obvious to have formulated the liposomes
with amounts effective to suppress macrophages and treat inflammation
because Monkkonen teaches that this is the purpose of its liposomes (FF6).
As discussed above, such amounts would treat restenosis because the
mechanism of action described by Monkkonen (FF6) and in the
Specification are the same (FF1, FF2).
2. OBVIOUSNESS
Monkkonen does not describe a bisphosphonate which is alendronate
as recited in claims 15 and 24—26.
FF9. However, Rogers discloses a number of bisphosphonates
including clodronate and alendronate, and teaches that alendronate causes
apoptosis in a macrophage-like cell line. Rogers, Abstract; Fig. 2 (Fig. 2).
See also Spec. 11:14—18.
It would have been obvious to one of ordinary skill in the art to have
utilized the bisphosphonate alendronate in place of the bisphosphonate
clodronate for alendronate’s expected macrophage suppressing affect, i.e.,
apoptosis would result in the celFs death, thereby suppressing its function.
It is obvious to utilize a prior art element for its established function. KSR
Inti Co. v. Teleflex Inc., 550 U.S. 398, 417 (2007).
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With respect to claims 24—26, which recites that the alendronate is a
salt:
FF10. DE ’890 teaches that bisphosphonates can be in salt form. DE
’890, p. 2,111,3,6.
Claims 4, 22
Dependent claims 4 and 22 recite that the composition of claims 1 and
15, respectively, further comprises a stabilizer.
FF11. DE ’890 teaches “saccharose” (sucrose) and sodium carbonate
buffer in clodronate liposomes. Id. at 3 (“Example”).
The Specification does not limit the stabilizers utilized in its
liposomes. Spec. 3:20—24. Consequently, we find, as the Examiner did
(Final Rej. 6), that sucrose and buffer can serve as stabilizers. It would have
been obvious to one of ordinary skill in the art to have included sucrose and
buffer in liposomes because DE ’890 teaches that they are conventional
components of a liposome preparation.
SUMMARY
1. The § 103 rejection of claims 1, 3, 4, 6, 15, 22, and 24—26 as
obvious in view of DE ’890 and Monkkonen (1994) is reversed.
Pursuant to 37 C.F.R. § 41.50(b):
2. Claims 1,3, and 6 are rejected under 35 U.S.C. § 102(b) as
anticipated by, or alternatively, under 35 U.S.C. § 103(a) as obvious in view
of, Monkkonen (1994). Medford is cited as evidence.
4. Claims 4, 15, 22, and 24—26 are rejected under 35 U.S.C. § 103 as
obvious in view of Monkkonen (1994), Rogers, and Medford.
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NEW GROUNDS OF REJECTION
This Decision contains new grounds of rejection pursuant to 37 C.F.R.
§ 41.50(b) (effective September 13, 2004, 69 Fed. Reg. 49960 (August 12,
2004), 1286 Off. Gaz. Pat. Office 21 (September 7, 2004)). 37 C.F.R. §
41.50(b) provides that “[a] new ground of rejection pursuant to this
paragraph shall not be considered final for judicial review.”
37 C.F.R. § 41.50(b) also provides that the Appellants, WITHIN
TWO MONTHS FROM THE DATE OF THE DECISION, must exercise
one of the following two options with respect to the new ground of rejection
to avoid termination of the appeal as to the rejected claims:
(1) Reopen prosecution. Submit an appropriate amendment of the
claims so rejected or new evidence relating to the claims so rejected,
or both, and have the matter reconsidered by the Examiner, in which
event the proceeding will be remanded to the Examiner. . . .
(2) Request rehearing. Request that the proceeding be reheard under
§ 41.52 by the Board upon the same record. . .
The amendment and/or new evidence under 37 C.F.R. § 41.50(b)(1),
or the request for rehearing under 37 C.F.R. § 41.50(b)(2), must be filed
within 2 months from the date of the Board’s decision. In accordance with
37 C.F.R. § 41.50(f), this 2-month time period may not be extended by the
filing of a petition and fee under 37 C.F.R. § 1.136(a), but only under the
provisions of 37 C.F.R. § 1.136(b).
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a)(l)(iv).
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REVERSED; 37 C.F.R. $ 41.50(b)
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