Ex Parte Whitfield et al

Patent Trial and Appeal Board

Mar 30, 2017

12636718 (P.T.A.B. Mar. 30, 2017)

United States Patent and Trademark Office
UNITED STATES DEPARTMENT OF COMMERCE
United States Patent and Trademark Office
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Alexandria, Virginia 22313-1450
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APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO.
12/636,718 12/12/2009 Nicola Whitfield 386541-QD14 (129543) 1907
27148 7590 04/03/2017
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PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte NICOLA WHITFIELD, JAAP KOOPMAN, and
JOS GRIMBERGEN1
Appeal 2015-003740
Application 12/636,718
Technology Center 1600
Before FRANCISCO C. PRATS, TAWEN CHANG, and
DEVON ZASTROW NEWMAN, Administrative Patent Judges.
CHANG, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134(a) involving claims to dry
powder fibrin sealant compositions and methods for preparing the same,
which have been rejected as anticipated and/or obvious. We have
jurisdiction under 35 U.S.C. § 6(b).
We REVERSE.
1 Appellants identify the Real Party in Interest as ProFibrix BV, a wholly-
owned subsidiary of The Medicines Company, and Quadrant Drug Delivery
Limited, a subsidiary of Vectura Group pic. (Appeal Br. 2.)
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Appeal 2015-003740
Application 12/636,718
STATEMENT OF THE CASE
Claims 1 and 43—66 are on appeal. Claim 1 is illustrative and
reproduced below:
1. A dry powder fibrin sealant composition, comprising:
a mixture of first microparticles that comprise fibrinogen
and trehalose, and
second microparticles that comprise thrombin and
trehalose,
wherein trehalose is the only stabilizing sugar in the first
microparticles and second microparticles, and
wherein the concentration of trehalose in the first
microparticles is sufficient to preserve at least 70% of fibrinogen
activity after exposure of the first microparticles to a 25 kGy dose
of gamma irradiation delivered at a rate of 8 kGy/hour.
(Appeal Br. 31 (Claims App’x).)
The Examiner rejects claims 1, 43—46, and 50-52 under 35 U.S.C.
§ 102 as being unpatentable over Maggos.2 (Ans. 2.)
The Examiner rejects claims 1 and 43—66 under 35 U.S.C. § 103(a) as
being unpatentable over Maggos and Heath.3 (Ans. 3.)
I.
Issue
The Examiner has rejected claims 1, 43—46, and 50—52 under
35 U.S.C. § 102 as being anticipated over Maggos. The Examiner finds that
Maggos teaches that Fibrocaps powder which contains fibrinogen and
thrombin derived from human plasma is as effective as marketed
fibrin sealants at stopping bleeding. Also, he teaches [] [Fjibrocaps
formulated using spray drying, which makes small hollow particles of
2 Christopher Maggos, Emerging Company Profile, ProFibrix: Hemostatic
sprinkles, Biocentury, The Bernstein Report on BioBusiness A15
(March 26, 2007).
3 Heath et al., U.S. Patent No. 6,113,948, issued Sep. 5, 2000.
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Application 12/636,718
thrombin and fibrinogen microsphere. Trehalose carbohydrate is
mixed in during the process. Trehalose prevents proteins from
denaturation and stabilizes them in their active conformation [] which
also allows them to go back into solution very rapidly. In addition,
Maggos teaches that Fibrocaps powder is stored at room temperature
and requires no preparation, and thus, can be “sprinkled” onto a
wound as soon as bleeding starts. While Maggos does not teach that
70% of fibrinogen activity remains after treatment with gamma rays[,]
or the amount of humidity [, these] are intrinsic properties of the
composition taught by Maggos.
(Ans. 2 (citations omitted).)
Appellants contend among other things that Maggos does not disclose
a concentration of trehalose in the first microparticles sufficient to preserve
at least 70% of fibrinogen activity after exposure of the first microparticles
to the dose of gamma radiation recited in claim 1. (Appeal 8—12.)
The issue with respect to this rejection is whether Maggos explicitly
or inherently disclose each element of claim 1.
Analysis
We find that Appellants have the better position. “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). The Examiner agrees that Maggos does not explicitly teach that
“70% of fibrinogen activity remains after treatment with gamma rays.”
(Final Act. 2, 3—4.) However, the Examiner argues that this is an intrinsic
property of the formulation taught in Maggos. (Ans. 6—7.)
We are not persuaded. “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 to establish inherency.”
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Application 12/636,718
Scaltech Inc. v. Retec/Tetra L.L.C., 178 F.3d 1378, 1384 (Fed. Cir. 1999)
(citations omitted). In this case, Maggos discloses that “trehalose prevents
proteins from denaturing and stabilizes them in their active conformation” in
the spray-dried Fibrocaps formulation discussed in the reference. (Maggos,
third column.) However, Maggos does not disclose the actual concentration
of trehalose present. While the Specification suggests that at least some
concentrations of trehalose that stabilizes fibrinogen during spray drying
may also work to preserve 70% of fibrinogen activity after exposure of
fibrinogen-trehalose microparticles to gamma radiation (Spec. Example 2),
Appellants have provided evidence in the form of expert declarations that
concentration(s) of trehalose used to stabilize fibrinogen and
thrombin against moderate thermal stress and water-loss in the
composition described in Maggos ... are not necessarily, i.e.,
as a matter of certainty rather than of probability, the
concentrations of trehalose required to stabilize these proteins
against gamma irradiation delivered at the dose and dose rate
stated in the claims.
(Lee Deck4117.) In particular, Dr. Lee explains that “the mechanism of
damage caused by ionizing radiation is different from that caused by thermal
stress and dehydration.” (Id. at 121; see also id. at || 22—23.)
The Examiner responds that the Specification does not provide
additional teaching beyond what is described by Maggos and that the
compositions taught in the Specification and Maggos are identical because
both relate to the trademarked Fibrocaps™ composition. (Ans. 6—7.) These
arguments are not persuasive. While Maggos and the Specification both
disclose a spray-drying process involving trehalose for formulating thrombin
4 Declaration of Professor Geoffrey Lee, Ph.D. under 37 C.F.R. § 1.132 (Jan.
25,2014) (“Lee Decl.”).
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Application 12/636,718
and fibrinogen microspheres, the Specification provides additional
information in the form of starting concentrations of trehalose and
fibrinogen and spray-drying parameters that according to the Specification
result in trehalose-fibrinogen microparticles retaining at least 70% of
fibrinogen activity after exposure to the dose of gamma radiation recited in
claim 1. (See, e.g., Spec. Example 2.) Neither can we conclude that the
compositions of Maggos and the Specification are substantially identical
(and thus have the same intrinsic properties) merely because both are
referred to by the same trademarked name. Cf. Manual of Patent Examining
Procedure § 608.0l(v) (“The relationship between mark or trade name and
the product ... is sometimes indefinite, uncertain, and arbitrary. [T]he
formula or characteristic of a product may change . . . and yet it may
continue to be sold under the same mark or trade name.”).)
Accordingly, we reverse the Examiner’s rejection of claim 1 as
anticipated by Maggos. Because claims 43^46 and 50-52 all depend
directly or indirectly from claim 1, we reverse the Examiner’s anticipation
rejection of those claims for the same reasons.
II.
Issue
The Examiner has rejected claims 1 and 43—66 under 35 U.S.C.
§ 103(a) as being obvious over Maggos and Heath. In addition to the
findings regarding Maggos discussed above, the Examiner finds that
[Heath] teaches the preparation of microparticles comprising
fibrinogen or thrombin [and] spray drying proteins in the
presence of excipients such as sugars including sucrose, lactose,
or ma[n]nitol or any other protein stabilizer^] and [also teaches]
that the sugar may have a beneficial effect in wound healing.
[Heath] teaches [a] formulation of microparticles containing
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Application 12/636,718
fibrinogen stabilized with sucrose loaded at 20%, and
microparticles loaded with thrombin stabilized with D-
man[n]itol. Said thrombin microparticle displays 91.86
Unit[s]/100 mg or 918.6 Units/g. [Heath] teach[es] that the
composition can be sterilized with gamma-radiation and the
prepared microparticles of thrombin and fibrinogen are mixed
in a ratio 1:1. Finally, [Heath] teaches the use of the
microparticles composition as a dry powder sealant in surgery
and to repair traumatic injuries among others.
(Ans. 3 (citations omitted).)
The Examiner also finds that Heath provides a skilled artisan with
“motivation to add sugars as stabilizer in formulation of microparticles
containing thrombin and fibrinogen,” while Maggos motivates the skilled
artisan “to use, in particular, trehalose in formulating microparticles of
firbrinogen and thrombin as he teaches the stability at room temperature and
the effectiveness of the composition for treat wounds.” (Id.) Accordingly,
the Examiner concludes that
it would have been obvious at the time of invention to prepare
fibrinogen and thrombin solutions containing trehalose as
solubilizing and/or stabilizing agent and use the solution for the
preparation of microparticles as described in [Heath] and make
suitable composition of the two microparticles to use as sealant
to prevent bleeding in surgical [procedures] or for treating
trauma patents. It would have been further obvious to one of
ordinary skill in the art to optimize the loading of fibrinogen in
the microparticles, the sterilization conditions, and the amount
of [trehalose] needed for optimal activity at the end of the
manufacturing processes. The remaining activity of fibrinogen
can be evaluated by any known method after sterilization.
(Id. at 3 4.)
Appellants contend that “[n] either Heath nor Maggos, taken alone or
in combination, discloses a dry powder fibrin sealant in which trehalose is
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Application 12/636,718
‘the only stabilizing sugar in the first microparticles and second
microparticles’, and the concentration of trehalose in the first microparticles
is sufficient to preserve at least 70% of fibrinogen activity after exposure of
the first microparticles to [the dose of gamma radiation recited in claim 1].”
(Appeal Br. 15 (footnote omitted).) Appellants contend that there would be
no reasonable expectation that such a dry powder fibrin sealant could
successfully be produced. {Id. at 15—23.) Appellants further contend that
microparticles made with trehalose have “unexpectedly superior properties
compared to microparticles made with sucrose, and that the claimed
composition as a whole have unexpectedly superior properties compared to
the prior art Heath compositions.” {Id. at 24.)
The issue with respect to this rejection is whether the evidence of
record supports the Examiner’s conclusion that the claims are prima facie
obvious over the combination of Maggos and Heath and, if so, whether
Appellants have provided evidence of unexpected results that, when
considered together with the evidence of obviousness, suffices to support a
conclusion of non-obviousness.
Analysis
On balance we find Appellants to have the better argument:
Appellants have provided evidence of unexpected results that the Examiner
has failed to address.
In particular, Appellants cite to Table 2 of the Specification to show
that Trehalose-Fibrinogen microparticles retained greater amount of
bioactivity (73%) than Sucrose-Fibrinogen microparticles (55.5%) after
gamma irradiation, and that the combination of thrombin and fibrinogen
microparticles made with trehalose achieved higher clot strength than that
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Application 12/636,718
made with sucrose after sterilization with gamma irradiation. (Appeal Br.
24—30; Spec. Table 2.) Appellants further cite testimony from Drs.
Koopman, Johnson, and Lee that the difference between trehalose and
sucrose described above are unexpected in light of similar levels of
protection trehalose and sucrose provides against dry heat sterilization and
further in light of the unknown mechanism by which trehalose protects
against gamma irradiation. (Appeal Br. 25—30; Koopman Decl.5 Tflf 48—52;
Johnson Decl.6 41—49; Lee Decl. 29—34.) Appellants also cite
Dr. Koopman’s further testimony that “microparticles made with trehalose
retain their stability over time unexpectedly better than microparticles made
with sucrose, when the particles are stored at room temperature.” (Appeal
Br. 27; Koopman Decl. Tflf 53—54.)
The Examiner argues that
[there are no] unexpected results in view of the fact that
Maggos teaches the claimed composition. The composition
taught by Maggos would be expected to be sterilized by
gamma-radiation because the regulatory requirements for its
use. The discovery of a property of a known composition does
not make it novel or non-obvious over the prior art of record.
In addition, the concentration of trehalose alone or in
combination with other non-sugar stabilizer is subjected to
optimization by one of ordinary skill in the art for the
sterilization condition required by regulatory agencies.
(Ans. 10.) We are not convinced. As discussed above with respect to the
anticipation rejection, the Examiner has not established a prima facie case
that Maggos teaches the claimed composition. Furthermore, to the extent
5 Declaration of Jaap L. Koopman, Ph.D. under 37 C.F.R. § 1.132
(Aug. 19, 2012) (“Koopman Decl.”).
6 Declaration of Richard A. Johnson, Ph.D. under 37 C.F.R. § 1.132
(Apr. 9, 2013) (“Johnson Deck”).
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Application 12/636,718
the Examiner’s argument is that Maggos’ composition as optimized by a
skilled artisan would suggest the claimed composition, we note that
applicants are not required to compare claimed invention to product
suggested by prior art to show unexpected results, because doing so “would
amount to requiring comparison of the results of the invention with the
results of the invention.” See In re Chapman, 357 F.2d 418, 422 (CCPA
1966).
Accordingly, we reverse the Examiner’s rejection of claims 1 and
43—66 as obvious over Maggos and Heath.
SUMMARY
For the reasons above, we reverse the Examiner’s decision rejecting
claims 1 and 43—66.
REVERSED
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