Ex Parte Shi et al

Board of Patent Appeals and Interferences

Jul 16, 2010

10132542 (B.P.A.I. Jul. 16, 2010)

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.
10/132,542 04/24/2002 Riyi Shi 290.00440101 1340
26813 7590 07/16/2010
MUETING, RAASCH & GEBHARDT, P.A.
P.O. BOX 581336
MINNEAPOLIS, MN 55458-1336
EXAMINER
FUBARA, BLESSING M
ART UNIT PAPER NUMBER
1618
MAIL DATE DELIVERY MODE
07/16/2010 PAPER
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.
PTOL-90A (Rev. 04/07)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte RIYI SHI and RICHARD B. BORGENS
__________

Appeal 2010-002049
Application 10/132,542
Technology Center 1600
__________

Before DONALD E. ADAMS, JEFFREY N. FREDMAN, and
STEPHEN WALSH, Administrative Patent Judges.

WALSH, Administrative Patent Judge.

DECISION ON APPEAL1
This is an appeal under 35 U.S.C. § 134(a) involving claims to a
method for treating a patient with an injury to its spinal cord or sciatic nerve.

1 The two-month time period for filing an appeal or commencing a civil
action, as recited in 37 C.F.R. § 1.304, or for filing a request for rehearing,
as recited in 37 C.F.R. § 41.52, begins to run from the “MAIL DATE”
(paper delivery mode) or the “NOTIFICATION DATE” (electronic delivery
mode) shown on the PTOL-90A cover letter attached to this decision.

Appeal 2010-002049
Application 10/132,542

2
The Patent Examiner rejected the claims as obvious. We have jurisdiction
under 35 U.S.C. § 6(b). We reverse.

STATEMENT OF THE CASE
The invention concerns method of treating an injured spinal cord or
sciatic nerve in mammals by administering an effective amount of a
composition comprising at least one polyalkylene glycol, such as
polyethylene glycol (PEG), by way of the patient’s vascular system to the
site of the injury. (Spec. 5-6). The composition of the invention is delivered
using either an intravascular, intramuscular, subcutaneous, or intraperitoneal
injection. (Id. at 6). The Specification explains that PEG appears to more
uniformly bathe the injury site when delivered by the blood supply than
when it is applied to the injury directly. (Id.). Additionally, the
Specification describes as an “unexpected finding” the observation that the
recovery of functions “has been identical to that previously determined in
response to topical (direct) application of PEG to the site of nerve tissue
injury.” (Id. at 7).
Claims 5, 9, 10, 12, 14-16, 40, 41, 74, 82 and 86-89, which are all the
pending claims, are on appeal. Claims 82, 87, 88 and 89 are representative
and read as follows:
82. A method for treating a mammalian patient having suffered an injury
to its spinal cord or sciatic nerve, the method comprising administering an
effective amount of a composition comprising at least one polyalkylene
glycol selected from the group consisting of polymethylene glycol,
polyethylene glycol, polypropylene glycol, polybutylene glycol,
polypentylene glycol, polyhexylene glycol, polyheptylene glycol,
polyoctylene glycol, polynonylene glycol, and polydecylene glycol, and
branched and structural isomers thereof to the patient so that the
Appeal 2010-002049
Application 10/132,542

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polyalkylene glycol is delivered by way of the patient's vascular system to
the site of the injured spinal cord or sciatic nerve tissue,
wherein delivery by way of the patient's vascular system is effected
using a technique selected from the group consisting of intravascular,
intramuscular, subcutaneous, and intraperitoneal injection, and
wherein the polyalkylene glycol is at least about 30% by weight in the
composition.

87. The method of claim 82, wherein the effective amount of a
composition comprising at least one polyalkylene glycol is effective to
restore nerve impulse conduction through the injured spinal cord or sciatic
nerve tissue.

88. The method of claim 87, wherein the restoration of nerve impulse
conduction is evidenced by one or more of a detectable increase in
conduction action potentials, observation of anatomical continuity,
restoration of more than one spinal root level, and an increase in reflex
behavior.

89. A method for treating a mammalian patient having suffered an injury
to its spinal cord or sciatic nerve, the method comprising administering an
effective amount of a composition comprising at least one polyalkylene
glycol selected from the group consisting of polyrnethylene glycol,
polyethylene glycol, polypropylene glycol, polybutylene glycol,
polypentylene glycol, polyhexylene glycol, polyheptylene glycol,
polyoctylene glycol, polynonylene glycol, and polydecylene glycol, and
branched and structural isomers thereof to the patient so that the
polyalkylene glycol is delivered by way of the patient's vascular system to
the site of the injured spinal cord or sciatic nerve tissue,
wherein delivery by way of the patient's vascular system is effected
using a technique selected from the group consisting of intravascular,
intramuscular, subcutaneous, and intraperitoneal injection, wherein the
polyalkylene glycol is at least about 30% by weight in the composition; and
wherein the polyalkylene glycol adheres to the injured spinal cord or sciatic
nerve tissue.

Appeal 2010-002049
Application 10/132,542

4
The Examiner rejected the claims under 35 U.S.C. § 103(a) over
Borgens2 and Linden3.

OBVIOUSNESS
The Issue
The Examiner’s position is that Borgens disclosed the topical
application of 50% polyethylene glycol (PEG) to the site of a spinal cord
injury in a guinea pig. (Ans. 4). The Examiner found that Borgens
disclosed that its method of administering PEG provided an effective
treatment of the injury and restored nerve impulse. (Id. at 4-5). The
Examiner also found that Borgens did not teach administration of its PEG
composition by intravascular, intramuscular, subcutaneous or intraperitoneal
routes. (Id. at 5). However, the Examiner found that Linden disclosed that
it was known in the art that compositions containing PEG had been
“administered systemically or intravenously or intraperitoneally to treat
injuries to the spinal cord.” (Id.).
Appellants contend that the Examiner did not establish a prima facie
case of obviousness and assert that topical delivery of an active ingredient is
“distinctly different” and “not readily interchangeable” with “delivery by
way of a patient’s vascular system … using a technique selected from the
group consisting of intravascular, intramuscular, subcutaneous and
intraperitoneal injection, as claimed….” (App. Br. 8). Appellants assert that

2 Richard B. Borgens et al., “Immediate recovery from spinal cord injury
through molecular repair of nerve membranes with polyethylene glycol.” 14
FASEB JOURNAL, 27- 35 (2000)
3 US Patent No. 6,232,297 B1 issued to Joel M. Linden, et al., May 15,
2001.
Appeal 2010-002049
Application 10/132,542

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Linden disclosed PEG only as a carrier and not “as an active ingredient for
the treatment of spinal cord injuries.” (Id.) According to Appellants, “active
ingredients and inert carriers are not readily interchangeable.” (Id. at 9).
Further, Appellants argue that their claimed delivery method unexpectedly
resulted in a selective adherence of the polyalkylene glycol to the injured
nerve tissue with little or no adherence to undamaged nerve tissue. (Id. at
12-13).
The issues with respect to this rejection are: whether the record
evidence supports the Examiner’s conclusion that the cited references would
have made the claimed compositions obvious, and if so, whether Appellants
have provided evidence of unexpected result that outweighs the evidence
supporting the prima facie case of obviousness.
Findings of Fact
1. Borgens topically applied an aqueous solution of PEG to the site of a
severe compression injury in the spinal cord of adult guinea pigs.
(Borgens, 28).
2. Borgens disclosed that its aqueous solution of PEG comprised 50% by
weight of PEG in distilled water. (Id.).
3. Borgens disclosed that topical application of its PEG solution to the
guinea pig spinal cord injury site resulted in an immediate recovery of nerve
impulse conduction and a progressive recovery of behavioral function of the
cutaneous trunci muscle reflex. (Id. at 32).
4. Borgens did not disclose administering its composition via
intravascular, intramuscular, subcutaneous or intraperitoneal injection.
Appeal 2010-002049
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5. Linden disclosed methods and compositions to treat inflammatory
activity in mammalian tissue with certain A2A adenosine receptor
antagonists. (Linden Abstract; col. 4, ll. 60-63).
6. Linden disclosed that the compositions of the invention may be
prepared as dispersions “in glycerol, liquid polyethylene glycols, triacetin,
and mixtures thereof and in oils.” (Id. at col. 11, ll. 46-48).
7. Linden disclosed that the liquid carrier or vehicle can be a solvent or
liquid dispersion medium comprising, for example, water, ethanol, a polyol,
for example, glycerol, propylene glycol, liquid [PEG], and the like. (Id. at
col. 11, ll. 59-62).
8. Linden disclosed that inflammatory responses that can be treated with
the method and composition of its invention included “cardiovascular
conditions including circulatory diseases induced or exasperated by an
inflammatory response, such as … spinal cord injury….” (Id. at col. 6, ll.
48-52).
9. Linden disclosed that the “compositions” of the invention may be
administered “orally or parenterally, by intravenous, intramuscular, topical
or subcutaneous routes.” (Id. at col. 10, l. 65 - col. 11, l. 2).
10. The Specification states: “an indirect administration of a
biomembrane fusion agent such as polyethylene glycol via the vascular
system of the patient unexpectedly results in a selective adherence of the
fusion agent … to the injured nerve tissue. There is little or no adherence to
undamaged nerve tissue.” (Spec. p. 31, ll. 14-20).
11. The Specification describes a test said to demonstrate that PEG can be
safely introduced into the bloodstream by several routes of administration,
including via a subcutaneous injection. (Id. at 71, ll. 4-21, Ex. 8).
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12. The results of the test are said to demonstrate “that PEG specifically
targets the spinal cord contusion independent of whether it is applied directly
to the exposed spinal injury, or by intravenous or subcutaneous injection.”
(Id.) The Specification teaches that “PEG specifically labeled the spinal
cord lesion but not undamaged tissues of adjacent regions” (Id. at 76, l. 23).

Principles of Law
Regarding the combination of references, it is proper to “take account
of the inference and creative steps that a person of ordinary skill in the art
would employ.” KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 418 (2007).
“A person of ordinary skill is also a person of ordinary creativity, not an
automaton.” (Id. at 421).
A prior art reference is said to teach away from an Applicant’s
invention “when a person of ordinary skill, upon reading the reference,
would be discouraged from following the path set out in the reference, or
would be led in a direction divergent from the path that was taken by the
applicant.” In re Gurley, 27 F.3d 551, 553 (Fed. Cir. 1994).
Evidence of unexpected results may rebut an Examiner’s case of
obviousness. See In re Rouffet, 149 F.3d 1350, 1355. (Fed. Cir. 1998).
“After evidence or argument is submitted by the applicant in response,
patentability is determined on the totality of the record, by a preponderance
of evidence with due consideration to persuasiveness of argument.” In re
Oetiker, 977 F.2d 1443, 1445 (Fed. Cir. 1992) (citations omitted).

Appeal 2010-002049
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Analysis
A. Claim 82
We are not persuaded by Appellants’ arguments that “the Examiner
has articulated no common sense reason to combine the teachings” of
Borgens and Linden. (See App. Br. 7). The Examiner found that Borgens
disclosed effectively treating a spinal cord injury by administering PEG
topically to the site of the injury. (Ans. 4). However, such administration
required a surgical procedure. Therefore, the Examiner reasoned that a
skilled artisan would have been motivated to modify Borgens’ topical
application of PEG to a less invasive route of administration, such as
through intravascular, intramuscular, subcutaneous or intraperitoneal
injection. (Ans. 5, 7-8). The Examiner found that Linden disclosed
compositions comprising PEG (FF-7) and expressly taught that the
“compositions” may be administered “parenterally, by intravenous,
intramuscular, topical or subcutaneous routes.” (FF-9).
To the extent that the Examiner stated that compositions comprising
PEG have been known to be administered intravenously or intraperitoneally
“to treat injuries to the spinal cord,” we do not find the statement expressly
supported by Linden. Rather, Linden disclosed that among the
“inflammatory responses” that can be treated with its invention are
“cardiovascular conditions including circulatory diseases induced or
exasperated by an inflammatory response, such as … spinal cord injury….”
(Linden, col. 6, ll. 48-52). Therefore, we find that Linden disclosed treating
an inflammatory response relating to a spinal cord injury, rather than the
injury itself.
Appeal 2010-002049
Application 10/132,542

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Nor do we find that Borgens taught away from adapting its PEG
composition for delivery via intravascular, intramuscular, subcutaneous or
intraperitoneal injection. As the Examiner (Ans. 5) and Appellants (App.
Br. 7) have acknowledged, Borgens did not address these forms of delivery.
Consequently, Borgens cannot be said to have discouraged such delivery,
see Gurley, 27 F.3d at 553, or criticized or discredited such an alternative
delivery technique.
However, our analysis does not end here. See Oetiker, 977 F.2d at
1445. Appellants contend that their “surprising and unexpected findings”
overcome any prima facie case of obviousness. (App. Br. 13). Specifically,
Appellants assert that they discovered that “indirect administration of a
biomembrane fusion agent [e.g., PEG] … via the vascular system of the
patient unexpectedly results in a selective adherence of the fusion agent …
to the injured nerve tissue. There is little or no adherence to undamaged
nerve tissue.” (Id., citing Spec. p. 31, ll. 14-20). The Specification provided
experimental evidence supporting these asserted unexpected findings. (FF-
11 and 12.)
We conclude the Examiner gave insufficient weight to the unexpected
results (Ans. 10-12), and conclude that the evidence is sufficient to show
nonobviousness on this record. See Rouffet, 149 F.3d at 1355.
B. Claims 87 and 88
As with the rejection of claim 82, we find that the Appellants’
evidence of unexpected results is sufficient to rebut the Examiner’s case of
obviousness. See Rouffet, 149 F.3d at 1355.
Appeal 2010-002049
Application 10/132,542

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C. Claim 89
As with the rejection of claims 82, 87 and 88, we find that the
Appellants’ evidence of unexpected results is sufficient to rebut the
Examiner’s case of obviousness. See Rouffet, 149 F.3d at 1355.

CONCLUSIONS OF LAW
The totality of record evidence does not establish that the claimed
methods would have been obvious.

SUMMARY
We reverse the rejection of claims 5, 9, 10, 12, 14-16, 40, 41, 74, 82
and 86-89.

REVERSED

lp

MUETING, RAASCH & GEBHARDT, P.A.
P.O. BOX 581336
MINNEAPOLIS MN 55458-1336