Ex Parte Gonzales et al

Patent Trial and Appeal Board

Oct 6, 2016

11534847 (P.T.A.B. Oct. 6, 2016)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
111534,847 0912512006
26875 7590 10/11/2016
WOOD, HERRON & EV ANS, LLP
2700 CAREW TOWER
441 VINE STREET
CINCINNATI, OH 45202
FIRST NAMED INVENTOR
Gilbert R. Gonzales
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.
SNHO- l 4US- l ll 6647
EXAMINER
PERREIRA, MELISSA JEAN
ART UNIT PAPER NUMBER
1618
NOTIFICATION DATE DELIVERY MODE
10/11/2016 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):
usptodock@whe-law.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte GILBERT R. GONZALES, DALE DEVORE,
and SURESH SRIVASTAVA
Appeal2014-007410
Application 11/534,847
Technology Center 1600
Before JEFFREYN. FREDMAN, RICHARD J. SMITH, and
JOHN E. SCHNEIDER, 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 an inflammatory condition. The Examiner rejected the claims as
obvious. We have jurisdiction under 3 5 U.S. C. § 6(b ). We affirm-in-part.
Statement of the Case
Background
"Plaques which form in the coronaries and other vessels comprise
inflammatory cells, smooth muscles cells, cholesterol, and fatty substances"
1 Appellants identify the Real Parties in Interest as Serene Oncology,
LLC and Brookhaven Science Associates, LLC (see App. Br. 2).
Appeal2014-007410
Application 11/534,847
(Spec. i-f 7). The "plaques can be characterized as stable or unstable. The
plaque is normally covered by an endothelial layer. When the endothelial
layer is disrupted, the ruptured plaque releases highly thrombogenic
constituent materials which are capable of activating the clotting cascade
and inducing rapid and substantial coronary thrombosis" (id.). "It has
recently been proposed that plaque instability, rather than the degree of
plaque build-up, should be the primary determining factor for treatment
selection." (Id.).
The Specification teaches "[ o ]nee unstable or vulnerable plaque has
been detected, it would be of significant benefit to provide methods for
treating that plaque to reduce the risk of rupture and abrupt closure" (Spec.
,-r 9).
The Claims
Claims 1-5, 8-16, 18-20, and 23-30 are on appeal.2 Claims 1 and 16
are representative and read as follows:
1. A method of treating an inflammatory condition in a
body lumen, said method comprising:
introducing to the body lumen a therapeutically effective
amount of a collagen Type I and/or Type III binding substance
bound to no-carrier-added tin-117m during a cascading rupture
of vulnerable plaque;
wherein the binding substance specifically binds to Type
I and/or Type III collagen exposed within the body lumen as a
result of the rupture of vulnerable plaque and wherein the tin-
117 m provides therapy to the vulnerable plaque.
2 Claim 1 7 was cancelled in the response filed Dec. 19, 2013 and
the Advisory Action indicated that for purposes of appeal, the
amendment would be entered (see Advisory Act. 1/10/14).
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Application 11/534,847
16. A therapeutic composition comprising:
a substance that binds Type I and/or Type III collagen;
and no-carrier-added tin-117m bound to the binding substance;
wherein the substance and the tin-117m are bound
together so that they can together bind to exposed Type I or
Type III collagen in regions of inflammation in body lumens;
and
wherein the collagen binding substance comprises an
antibody or a fragment of an antibody that specifically binds to
Type I or Type III collagen.
The issues
A. The Examiner rejected claims 1-5, 8-16, 18-20, and 23-30 under 35
U.S.C. § 103(a) as obvious over McBride,3 Qaim,4 Mausner,5 Fuster (2005),6
Fuster (1990),7 Rekhter, 8 Bode,9 Lammi, 10 and Nieuwenhuis11 (Ans. 2-8).
3 McBride et al., US 7,238,340 Bl, issued July 3, 2007 ("McBride").
4 Qaim and Dahler, Production of carrier-free 117mSn, 35 Int. J.
Applied Radiation and Isotopes 645-50 (1984) Abstract only
("Qaim").
5 Mausner et al., Nuclear data for production of 11 7mSnfor
biomedical application, 94 Radiation Effects 59---63 (1986)
Abstract only ("Mausner").
6 Fuster et al., Atherothrombosis and High-Risk Plaque, 46 J. Am.
College of Cardiology 937-54 (2005) ("Fuster (2005)").
7 Fuster et al., Atherosclerotic Plaque Rupture and Thrombosis, 82
Circulation Suppl. II 47-59 (1990) ("Fuster (1990)").
8 Rekhter, M., Collagen synthesis in atherosclerosis: too much and
not enough, 41 Cardiovascular Res. 376-84 (1999) ("Rekhter").
9 Bode, M., Characterization Of Type I And Type III Collagens In
Human Tissues 1-76 (2000) (Dissertation, University of Oulu)
("Bode").
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Application 11/534,847
B. The Examiner rejected claims 1-5, 8-16, 18-20, and 23-30 under 35
U.S.C. § 103(a) as obvious over McBride, Qaim, Mausner, Blankenberg, 12
von der Mark, 13 Fuster (2005), Fuster ( 1990), Bode, and Lammi (Ans. 8-
12).
Because the same issues, the same claims, and substantially the same
prior art are dispositive for both rejections, we will consider the rejections
together.
The Examiner finds that
At the time of the invention it would have been obvious to one
ordinarily skilled in the art that an amount of collagen available
for targeting, even if it is a small amount, will be present during
rupture repairs or the amount of collagen present will be large
in a patient with a bleeding disorder as the defect in the platelets
inhibits the binding of platelets to collagen[ Nieuwenhuis].
Thus, it would have been advantageous to utilize the 5D8- G9
monoclonal antibody of Lammi et al. as the targeting moiety of
the metal chelator/targeting moiety conjugates of McBride et al.
to specifically target the metal chelator/targeting moiety
conjugates of McBride et al. to atherosclerotic (relating to
atherosclerotic rupture) plaque.
(Ans. 7).
10 Lammi et al., Site-specific Immunostainingfor Type X Collagen in
Noncalcified Articular Cartilage of Canine Stifle Knee Joint, 31 Bone 690-
96 (2002) ("Lammi").
11 Nieuwenhuis et al., Human Blood platelets showing no response to
collagen fail to express surface glycoprotein Ia, 318 Nature 470-72 (1985)
("N ieuwenhuis").
12 Blankenberg et al., US 2003/0152513 Al, published Aug. 14, 2003
("Blankenberg").
13 von der Mark and Mollenhauer, Annexin V interactions with collagen, 53
CMLS Cell Mol. Life Sci. 539--45 (1997) ("von der Mark").
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Application 11/534,847
The issues with respect to this rejection are:
(i) Does the evidence of record support the Examiner's conclusion
that the prior art suggests administering "tin-117m during a cascading
rupture of vulnerable plaque" as required by claim 1?
(ii) Does the evidence of record support the Examiner's conclusion
that the prior art renders obvious a therapeutic composition comprising "a
substance that binds Type I and/or Type Ill collagen" bound to "no-carrier-
added tin-117m" as required by claim 16?
Findings of Fact
1. McBride teaches
reagents useful in preparing diagnostic and therapeutic
radiopharmaceutical agents. Specifically, the invention provides
reagents that are monoamine, diamide, thiol-containing
(MAD AT) metal chelators ... and complexes of such metal
chelators with isotopes of ... tin-117m ... Conjugates between
said metal chelating groups and a variety of specific targeting
moieties are also provided. Such conjugates are comprised of a
metal chelating group of the invention covalently linked to a
specific targeting molecule.
(McBride 5:54---65).
2. McBride teaches "the metal chelator and the targeting moiety
are linked via a linker which in certain embodiments comprises an amino
acid or peptide. Complexes of the metal chelate/targeting moiety conjugates
of the invention with radioisotopes ... including ... tin-117m ... are also
provided" (McBride 12:4--10).
3. McBride teaches that the "scintigraphic imaging agents of the
invention are also useful for imaging sites of infection, thrombosis ... and
atherosclerosis" (McBride 17:16-19).
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4. Blankenberg teaches "exogenously administered annexin V to
create a multi-functional molecular probe that can be simultaneously used
for imaging (localization of unstable plaque within the body) and therapy
(treatment of unstable plaque)" (Blankenberg i-f 28).
5. Blankenberg teaches that "annexin Vis labeled with both a
radioisotope such as technetium-99m and a photodynamic agent such as a
light absorbing porphyrin .... Targeted cells sensitized to light through the
localization of the annexin V complex are then selectively destroyed with a
limited laser pulse" (Blankenberg i-f 29).
6. Qaim teaches "[p]roduction of carrier-free 117mSn" and Mausner
teaches "better specific activity for reactor-produced 117msn can be obtained
by irradiating natural tin in the core of a reactor" (Qaim, abstract; Mausner,
abstract).
7. von der Mark teaches that "Annexin V was originally identified
as a collagen-binding protein .... The binding to native collagen types II
and X, and to some extent to type I as well, was confirmed using
recombinant annexin V" (von der Mark, abstract).
8. Fuster (2005) teaches "[p ]laque rupture is the most common
substrate for coronary thrombosis in humans" (Fuster (2005) 938, col. 1)
9. Fuster (2005) teaches "vulnerable plaque was defined as a
plaque with a fibrous cap <65 µm thick with an infiltrate of macrophages"
(Fuster (2005) 937, col. 2).
10. Fuster (2005) teaches "[t]hrombus organization mediated by
repaired collagen (type III) heals the rupture site" (Fuster (2005) 947, col. 1).
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Application 11/534,847
11. Fuster (1990) teaches that "deep vessel injury secondary to
plaque rupture or ulceration results in exposure of collagen, lipids, and other
elements of the vessel media, leading to relatively persistent thrombotic
occlusion and myocardial infarction" (Fuster (1990) 53, col. 2).
12. Rekhter teaches: "Human atherosclerotic plaques contain
mostly interstitial collagen types I and III ... 'too much' collagen leads to
arterial stenosis, while 'not enough' collagen makes atherosclerotic plaque
prone to rupture" (Rekhter 376, col. 1 to 2).
13. Bode teaches that both normal and atherosclerotic aorta contain
type I and type III collagen (see Bode 30).
14. Lammi teaches that for "different collagen types, the following
murine monoclonal antibodies were used: clone 5D8-G9 for type I (Amrad
Biotech, Boronia Victoria, Australia); clone E8 for type II; clone IE7-D7 for
type III (Amrad Biotech)" (Lammi 691, col. 2).
15. Nieuwenhuis teaches that:
The interaction of blood platelets with collagen is generally
considered to be of primary importance in the arrest of bleeding
and to have a role in the pathogenesis of thrombosis and
atherosclerosis. Following damage to the vascular
endothelium, circulating platelets come into contact with
exposed collagen fibrils in the sub-endothelium and spread
along it .... We now report a defect of the platelet plasma
membrane glycoprotein composition in a patient whose
platelets are totally unresponsive to collagen.
(Nieuwenhuis abstract).
Principles of Law
A prima facie case for obviousness "requires a suggestion of all
limitations in a claim," CFMT, Inc. v. Yieldup Int'! Corp., 349 F.3d 1333,
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1342 (Fed. Cir. 2003), and "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'! Co. v. Teleflex Inc., 550 U.S. 398,
418 (2007).
Analysis
Claim 1
Appellants contend that at "the time of the invention, tin-117m was
known ... but it was not known that tin-117m could treat vulnerable plaque"
(App. Br. 7). Appellants further contend that it was not known "that
collagen could be used as a target to treat vulnerable plaque during this
cascading rupturing event. If one administered the collagen binding tin-
117m compound, when the vulnerable plaque was not actually rupturing, it
would not bind to the vulnerable plaque" (id.).
The Examiner responds that:
The applicant concedes that collagen is exposed and is almost
immediately bound to platelets and thus an amount of collagen
is exposed for a time ( 1 minute). At the time of the invention it
would have been obvious to one ordinarily skilled in the art that
an amount of collagen available for targeting, even if it is a
small amount, will be present during rupture repairs or the
amount of collagen present will be large in a patient with a
bleeding disorder as the defect in the platelets inhibits the
binding of platelets to collagen[Nieuwenhuis]. Thus, it would
have been advantageous to utilize the 5D8-G9 monoclonal
antibody of Lammi et al. as the targeting moiety of the metal
chelator/targeting moiety conjugates of McBride et al. to
specifically target the metal chelator/targeting moiety
conjugates of McBride et al. to atherosclerotic (relating to
atherosclerotic rupture) plaque.
(Ans. 16-17).
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Application 11/534,847
We find that Appellants have the better position. We recognize that
McBride and Blankenberg suggest imaging of atherosclerotic lesions with
radioactive agents, including 117msn, linked to targeting moieties (FF 1-5);
that Fuster (2005), Rekhter, and Bode establish that collagens are part of
these lesions (FF 10, 12, 13); and that Lammi teaches specific monoclonal
antibodies that function as collagen targeting moieties (FF 14).
However, claim 1 has a specific timing step that requires the
introduction of the therapeutic agent "during a cascading rupture of
vulnerable plaque." As written, claim 1 essentially requires a physician to
have already determined that a cascading rupture of vulnerable plaque has
begun prior to treating with the therapeutic composition.
The Examiner provides no reason or suggestion in the art to
administer a therapeutic agent at that particular time point, after rupture of
plaque has begun, rather than prior to any rupture of vulnerable plaque.
While Fuster (1990) and Nieuwenhuis teach that platelets interact with
exposed collagen (FF 11, 15), neither of these references nor the other cited
prior art provides a reason to delay treatment until "during a cascading
rupture" rather than upon determination that vulnerable plaque exists. See
Mformation Technologies, Inc. v. Research in Motion Ltd., 764 F.3d 1392,
1398-99 (Fed. Cir. 2014) (A "claim 'requires an ordering of steps when the
claim language, as a matter of logic or grammar, requires that the steps be
performed in the order written, or the specification directly or implicitly
requires' an order of steps.")
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Claim 16
Appellants do not provide any arguments specific to the therapeutic
composition of claim 16. Claim 16 is drawn to a composition comprising a
Type I or Type III collagen antibody bound to no-carrier-added tin-117m.
McBride specifically teaches diagnostic agents comprising a peptide
targeting moiety and tin-117m (FF 1-2) that may be targeted to sites of
thrombosis and atherosclerosis (FF 3). Blankenberg similarly teaches a
composition comprising a radioactive agent and targeting moiety for
imaging plaque associated with atherosclerosis (FF 4--5). Qaim and
Mausner teach no-carrier-added tin-117m as a known equivalent (FF 6).
Fuster (2005), Rekhter, and Bode each teach that collagen Types I and
III are found in atherosclerotic lesions (FF 10, 12, 13) and Lammi teaches
that antibodies to collagen Types I and III were commercially available (FF
14).
Thus, we agree with the Examiner's finding it would have been
obvious, in the context of the composition claim 16, "to utilize the 5D8- G9
monoclonal antibody of Lammi et al. as the targeting moiety of the metal
chelator/targeting moiety conjugates of McBride et al. to specifically target
the metal chelator/targeting moiety conjugates of McBride et al. to
atherosclerotic (relating to atherosclerotic rupture) plaque" (Ans. 7).
In particular, we agree that the ordinary artisan, motivated by
McBride to use tin-117m linked to peptide targeting agents in diagnosis of
atherosclerosis, would have reasonably selected the collagen Type I and III
antibodies of Lammi as targeting agents because Fuster (2005), Rekhter, and
Bode teach that collagen Type I and III are components of atherosclerotic
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lesions and would thus serve as targets for the targeting moiety in a
diagnostic assay.
Appellants provide no evidence or argument rebutting the Examiner's
reasonable obviousness position for claim 16.
Conclusion of Law
(i) The evidence of record does not support the Examiner's conclusion
that the prior art suggests administering "tin-117m during a cascading
rupture of vulnerable plaque" as required by claim 1.
(ii) The evidence of record supports the Examiner's conclusion that
the prior art renders obvious a therapeutic composition comprising "a
substance that binds Type I and/or Type Ill collagen" bound to "no-carrier-
added tin-117m" as required by claim 16.
SUMMARY
In summary, we reverse the rejection of claims 1-5 and 8-15 under
35 U.S.C. § 103(a) as obvious over McBride, Qaim, Mausner, Fuster (2005),
Fuster ( 1990), Rekhter, Bode, Lammi, and Nieuwenhuis.
We affirm the rejection of claim 16 under 35 U.S.C. § 103(a) as
obvious over McBride, Qaim, Mausner, Fuster (2005), Fuster ( 1990),
Rekhter, Bode, Lammi, and Nieuwenhuis. Claims 18-20 and 23-30 fall
with claim 16.
We reverse the rejection of claims 1-5 and 8-15 under 35 U.S.C.
§ 103(a) as obvious over McBride, Qaim, Mausner, Blankenberg, von der
Mark, Fuster (2005), Fuster (1990), Bode, and Lammi.
We affirm the rejection of claim 16 under 35 U.S.C. § 103(a) as
obvious over McBride, Qaim, Mausner, Blankenberg, von der Mark, Fuster
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Application 11/534,847
(2005), Fuster (1990), Bode, and Lammi. Claims 18-20 and 23-30 fall with
claim 16.
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-IN-PART
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