Ex Parte Medof et al

Patent Trial and Appeal Board

May 31, 2016

12921308 (P.T.A.B. May. 31, 2016)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR
12/921,308 11/23/2010 M. Edward Medof
68705 7590 06/02/2016
TAROLLI, SUNDHEIM, COVELL & TUMMINO, LLP
1300 EAST NINTH STREET
SUITE 1700
CLEVELAND, OH 44114
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.
CWR-018227US PCT 1812
EXAMINER
ROGERS, JAMES L
ART UNIT PAPER NUMBER
1644
NOTIFICATION DATE DELIVERY MODE
06/02/2016 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):
rkline@tarolli.com
docketing@tarolli.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte M. EDWARD MEDOF, MICHAEL G. STAINIC,
KRISTINA V. THOMAS, JODI ARTH, FENQGI AN,
and JUANG HUANG 1
Appeal2014-005917
Application 12/921,3 08
Technology Center 1600
Before LORA M. GREEN, JEFFREY N. FREDMAN, and
RACHEL H. TOWNSEND, Administrative Patent Judges.
TOWNSEND, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims to methods
of treating T-cell mediated corneal inflammation, all of which have been
rejected as obvious. We have jurisdiction under 35 U.S.C. § 6(b ).
We affirm, but designate our affirmance as New Grounds of
Rejection.
STATEMENT OF THE CASE
Herpes stromal keratitis is initiated by viral infection of corneal cells.
(Spec. i-f 4.) The infection gives rise to host T-cell responses, including
1 Appellants identify the Real Party in Interest as Case Western Reserve
University. (Br. 2.)
Appeal2014-005917
Application 12/921,308
inflammation, to virally infected corneal cells, which results in corneal tissue
damage. (Id.) Topical steroids are used in current treatment to help
suppress the inflammatory response. (Id.) The claimed invention seeks to
treat T-cell mediated corneal inflammation by administering to the cornea of
the subject at least one complement antagonist in an amount effective to
substantially reduce or substantially inhibit at least one of T-cell
differentiation or T-cell cytokine expression. (Id. at i-f 6.)
Claims 10, 17, 26, and 292 are on appeal. Claims 10 and 26 are
independent and read as follows:
10. A method of treating T-cell mediated corneal inflammation
in a subject, the method comprising: administering to the
cornea of the subject at least one complement antagonist, the at
least one complement antagonist including an antibody directed
against C5aR and an antibody directed against C3aR; wherein
the at least one complement antagonist is administered at an
amount effective to substantially reduce or substantially inhibit
at least one of T -cell differentiation or T-cell cytokine
expression, and substantially reduce the interaction of C3a and
C5a with a C3a receptor (C3aR) and C5a receptor (C5aR) of
the T-cell.
(Br. 22.)
26. A method of treating T-cell mediated corneal inflammation
associated with Herpes stromal keratitis in a subject, the method
comprising: administering to the cornea of the subject at least one
complement antagonist, the at least one complement antagonist
including an antibody directed against C5aR and an antibody directed
against C3aR, wherein the complement antagonist is administered at
amount effective to substantially reduce or substantially inhibit at
least one of T-cell differentiation or T-cell cytokine expression
2 Claims 14, 16, and 28 are also pending, but stand withdrawn from
consideration. (Br. 2.)
2
Appeal2014-005917
Application 12/921,308
proximate the cornea, and substantially reduce the interaction of C3a
and C5a with a C3a receptor (C3aR) and C5a receptor (C5aR) of the
T-cell.
(Br. 23.)
The following grounds of rejection by the Examiner are before us on
review:
1. Claims 10 and 17 under 35 U.S.C. § 103(a) as unpatentable over
Fung3 and Jha, 4 as evidenced by Qazi. 5 (Final Action 3--4.)
2. Claims 26 and 29 under 35 U.S.C. § 103(a) as being unpatentable
over Fung, Jha, and Meyers-Elliot, 6 as evidenced by Qazi, and Stuart. 7
(Final Action 4--5.)
ANALYSIS
Regarding the rejection of claims 10 and 17, the Examiner finds that
Fung teaches a method of treating ocular diseases, including ocular
neovascularization affecting corneal tissue, by administering complement
3 Fung et al., WO 2007/056227 A2, published May 18, 2007.
4 Purushottam Jha, Puran S. Bora, and Nalini S. Bora, The role of
complement system in ocular diseases including uveitis and macular
degeneration, 44 Molecular Immunology, 3901 (2007).
5 Yureeda Qazi, Surekha Maddula, and Balamurali K. Ambati, Mediators of
ocular angiogenesis, 884 (4) Journal of Genetics, 495 (2009).
6 Roberta H. Meyers-Elliot and Patricia A. Chitjian, Immunopathogenesis of
corneal inflammation in herpes simplex virus stromal keratitis: role of the
polymorphonuclear leukocyte, 20 ( 6) Invest. Opthalmol. & Visual Science,
784 (1981).
7 Patrick M. Stuart, Brett Summers, Jessica E. Morris, Lynda A. Morrison,
and David A. Leib, CD8+ T cells control corneal disease following ocular
infection with herpes simplex virus type 1, Journal of General Virology,
2055 (2004).
3
Appeal2014-005917
Application 12/921,308
component inhibitors to a subject. (Final Action 3). According to the
Examiner, Qazi evidences that ocular neovascularization affecting corneal
tissue disclosed in Fung is an ocular disease mediated by T-cells. (Final
Action 3; Ans. 6.) The Examiner finds that Fung teaches such complement
component inhibitors are, in one embodiment, "antibodies against C5aR and
C3aR," and that such antibodies would "necessarily reduce the interaction of
C3a and C5a with C3aR and C5aR of the T cell." (Final Action 3 (emphasis
in the original).) The Examiner also finds that Fung teaches administration
of the complement component inhibitors locally, such as by an eye wash
solution. (Id.) The Examiner notes that Fung does not specifically identify
administration of the complement component inhibitor ("which includes an
antibody directed against C5aR and an antibody directed against C3aR") to
the cornea of the subject. (Id.) The Examiner explains, however, that Jha
fills that gap. (Id.)
The Examiner explains that Jha discloses that complement
components of both the classical and alternative complement pathways are
present in normal cornea and that the cornea has the capability of activating
the complement cascades in response to infection. (Id.) The Examiner also
finds Jha teaches that the complement pathway components play an
important role in the development of corneal inflammation and also that
complement inhibition is a relevant therapeutic target in the treatment of
various ocular diseases involving corneal inflammation. (Final Action 3, 5.)
The Examiner concludes from these findings that it would have been
obvious to administer to the cornea "an antibody directed against C5aR and
C3aR in the treatment of corneal inflammation ... due to an ocular disease
4
Appeal2014-005917
Application 12/921,308
such as ocular neovascularization in an ophthalmic preparation as taught by
Fung." (Final Action 3 (emphasis added).)
The Examiner observes that the teachings of Fung and Jha differ from
claims 26 and 29 in that they do not show treating T-cell mediated corneal
inflammation associated with Herpes stromal keratitis. (Final Action 4.)
According to the Examiner, though, Meyers-Elliot, as evidenced by Stuart,
renders the claimed treatment for that T-cell mediated disorder obvious.
(Final Action 4.) The Examiner finds Meyers-Elliot discloses
immunopathogenesis of corneal inflammation in herpes simplex virus
stromal keratitis ("HSV keratitis") and that Stuart discloses HSV keratitis is
T-cell mediated. (Id.) Regarding the immunopathogenesis, the Examiner
explains that Meyers-Elliot teaches complement is localized in the cornea of
subjects with stromal infiltrates and that complement pathway components
play an essential role in HSV keratitis development. (Id.) The Examiner
concludes from the foregoing that one of ordinary skill in the art would have
been motivated to treat HSV keratitis using the Fung method as modified by
Jha, i.e., administering antibodies to C3aR and C5aR to the cornea to treat
corneal inflammation attributable to ocular diseases, because Fung and Jha
teach such a method is capable of treating ocular diseases involving corneal
inflammation induced by complement. (Id.)
In both of the§ 103(a) rejections, the Examiner interpreted the claims
as "not limited to administration of both an antibody against C5aR and C3aR
because the claims recite administering 'at least one complement antagonist
including an antibody directed against C5aR and an antibody directed
against C3aR."' (Ans. 6.) We disagree with that claim interpretation.
5
Appeal2014-005917
Application 12/921,308
Independent claims 10 and 26 both require that the "at least one complement
antagonist" that is administered "includ[ es] an antibody directed against
C5aR and an antibody directed against C3aR." (Br. 22, 23.) The natural
reading of the term "including" is that the group of ensuing elements are
essential as part of the whole being considered. MPEP 2111.03 (noting that
"including" is synonymous with "comprising" and is inclusive while not
excluding additional elements); see also Genentech, Inc. v. Chiron Corp.,
112 F.3d 495, 501 (Fed. Cir. 1997) ("Comprising" is a term of art used in
claim language which means that the named elements are essential, but other
elements may be added and still form a construct within the scope of the
claim.) Beyond that, claims 10 and 26 also require that the at least one
complement antagonist is present in an amount that "substantially reduce[ s]
the interaction of C3a and C5a with a C3a receptor (C3aR) and C5a receptor
(C5aR) of the T-cell." (Br. 22, 23 (emphasis added).) This functional
condition of the at least one complement antagonist further supports
interpreting that it require the presence of an antibody directed against C5aR
as well as an antibody directed against C3aR.
Though we disagree with the Examiner's claim interpretation, we
affirm the Examiner's conclusion that claims 10 and 17 are obvious under
35 U.S.C. § 103(a) over Fung, Jha, and Qazi, and that claims 26 and 29 are
obvious under 35 U.S.C. § 103(a) over Fung, Jha, Meyers-Elliot, Qazi, and
Stuart. However, because our reasoning differs to some degree from that of
the Examiner, we will designate our affirmance as a New Grounds of
Rejection in order to provide Appellants with a fair opportunity for further
prosecution, if so desired. See In re Kronig, 539 F.2d 1300, 1302 (CCPA
6
Appeal2014-005917
Application 12/921,308
1976) ("[T]he ultimate criterion of whether a rejection is considered 'new' in
a decision by the board is whether appellants have had fair opportunity to
react to the thrust of the rejection.").
Appellants contest both of the Examiner's rejections for similar
reasons but under separate headings. To the extent that the arguments raise
the same or similar issues, we treat them together.
According to Appellants, Fung and Jha teach inhibiting intraocular
inflammation by inhibiting complement pathway. (Br. 9, 17-18.)
Appellants contend that one skilled in the art would not administer an
antibody directed against C5aR and an antibody directed against C3aR to the
cornea to treat T-cell mediated cornea inflammation based on the cited
references, because none of the references teach that an antibody directed
against C5aR and an antibody directed against C3aR can inhibit the
complement pathway when administered to the cornea. (Id.)
Because Appellants contend that Fung is concerned with inhibiting
complement pathway by inhibiting the classical and alternative complement
pathways, Appellants further contend it is unclear what Fung is referring to
with respect to C3aR and C5aR inhibitors. (Br. 5---6, 13-14.) Appellants
assert that an antibody directed against C3aR and C5aR would not inhibit
the classical or alternative complement pathways because C3aR and C5aR
"are receptors that are expressed by cells not proteins of the complement
cascade." (Br. 9, 18).
We disagree with Appellants' foundational argument that Fung is
limited to teaching complement inhibitors that inhibit the classical and
alternative complement pathways. While it may be true that Fung i-f 16
7
Appeal2014-005917
Application 12/921,308
indicates the complement inhibitors that can be used to treat ocular related
conditions or diseases "include those that inhibit the alternative pathway and
classical complement pathway" (Br. at 6), that is but one embodiment of
Fung. Fung i-f 16 makes clear that the complement inhibitors "are not limited
to" those inhibiting the alternative and classical complement pathways. The
complement inhibitors recited in Fung i-f 1 7 are "[a ]nother embodiment of
the [Fung] invention." That invention, as Appellants recognize, is broadly
directed to "complement inhibitors for the treatment of ocular related
conditions or diseases, such as age-related macular degeneration (AMD),
diabetic retinopathy, ocular angiogenesis (such as ocular neovascularization
affecting choroidal, corneal, or retinal tissue), and other ocular conditions
involving complement activation" (Br. 5, citing Fung i-f 15), and not
complement inhibitors "inhibiting the alternative and classical complement
pathways" to treat ocular related conditions or diseases.
We also disagree with Appellants' contention that Jha is limited to
teaching or suggesting complement inhibitors to inhibit ocular inflammation
are just those that inhibit the alternative and classical complement pathway.
(Br. at 9, 17.) Jha teaches that complement components are found in the
cornea and that the cornea can activate complement, which could cause
damage to the corneal tissue. (Final Action 3, citing 3902, 1st and 2nd i-fs
under section 3 .1, '"'Complement and corneal disease"). And Jha
specifically states that "complement inhibition is a relevant therapeutic
8
Appeal2014-005917
Application 12/921,308
target in the treatment of various ocular diseases." (Jha 3901 (Abstract);
Final Action 3.)8
We also disagree with Appellants that Fung only teaches that the
C5aR and C3aR inhibitors can be antibodies, not that those antibodies are
directed against C5aR or C3aR (Br. 5-6, 13-14). We find, as the Examiner
did, that Fung teaches complement inhibitors for the treatment of ocular
diseases include C3aR and C5aR inhibitors that are antibodies against C3aR
and C5aR. (Fung i-f 17.) We further agree with the Examiner that such
antibodies "would necessarily reduce the interaction of C3a and C5a with
C3aR and C5aR of the T-cell." (Final Action 3.)
Appellants also argue that not one of Fung, Jha, Qazi, 9 Meyers-Elliot
or Stuart teaches that an antibody directed against C5aR or C3aR "can be
administered to the cornea to treat T-cell mediated corneal inflammation, let
8 Jha provides several specific examples regarding complement inhibition as
a therapeutic target, including receptor antibodies, that the Examiner did not
specifically delineate, but which plainly support the statement in the abstract
that "complement inhibition is a relevant therapeutic target in the treatment
of various ocular diseases." See, e.g., Jha 3902-3903 (3.2 Complement and
autoimmune uveitis noting the protective effect of anti-CR3, which
specifically blocks the interaction between iC3b and its receptor CR3), Jha
3904 (3.3 Complement and age-related macular degeneration discussing
"Choroidal neovascularization (CNV), the hallmark lesion of wet AMD"
and the interplay between C3a and C5a and their respective receptors C3aR
and C5aR in reducing CNV through "reduced leukocyte recruitment and
VEGF expression").)
9 Appellants mention in passing that because Qazi was published after the
filing date of the application, it is not prior art. (Br. 7.) Appellants do not
contest, however, that Qazi shows what is inherent in Fung---ocular
neovascularization affecting corneal tissue is mediated by T-cells.
9
Appeal2014-005917
Application 12/921,308
alone that both an antibody directed against C5aR and an antibody directed
against C3aR is administered to the cornea to treat T-cell mediated corneal
inflammation." (Id. at 6-7, 14--15.) Appellants' argument does not
convince us that the Examiner's obviousness rejections are in error.
"Non-obviousness cannot be established by attacking references individually
where the rejection is based upon the teachings of a combination of
references. . . . [The reference] must be read, not in isolation, but for what it
fairly teaches in combination with the prior art as a whole." In re Merck &
Co., 800 F.2d 1091, 1097 (Fed. Cir. 1986). That none of the references
individually teach an antibody directed against C5aR or C3aR can be
administered to the cornea to treat T-cell mediated corneal inflammation is
not relevant to whether the references suggest the foregoing. As discussed
above, and as the Examiner found, Fung teaches the use of an antibody
directed against C5aR and C3aR as complement component inhibitors to
treat ocular diseases including those that affect corneal tissue, such as
corneal neovascularization. (Fung i-fi-f 15, 17; Final Action 3.) An antibody
that is directed against C5aR and C3aR would inherently inhibit complement
(C3a and C5a), i.e., inhibit C3a and C5a interaction with their respective
receptor. We conclude, like the Examiner, that Jha provides the motivation
to administer antibodies directed against C5aR and C3aR to the cornea to
treat T-cell mediated corneal inflammation. (Final Action 3.)
While we disagree with the Examiner's conclusion that claims 10 and
26 do not require both antibodies against C5aR and C3aR be present in the
at least one complement antagonist, we disagree with Appellants that no
reference teaches this limitation (Br. 6-7, 14-16). Fung states that "[a ]nother
10
Appeal2014-005917
Application 12/921,308
embodiment of the present invention relates to the use of C5aR and C3aR
inhibitors, such as antibodies .... " (Fung i-f 17 (emphasis added).) Indeed,
the Examiner so found, stating: "Fung further teaches that in one
embodiment the complement inhibitors are antibodies against C5aR and
C3aR (i-fl 7)." (Final Action 3 (emphasis in the original).) Fung also teaches
that treatment of ocular diseases such as choroidal neovascularization can be
by administration of a therapeutically acceptable dose of "an antibody, or
antibodies." (Fung i-f 124.) To the extent the use of both anti-C5aR and anti-
C3aR antibodies together are not expressly taught to be used together in
Fung, such would have been obvious to one having ordinary skill in the art
in light of Fung's disclosure that more than one antibody can be
administered in therapeutic amounts.
Appellants assert that even if the references suggested administering
an anti-C5aR and anti-C3aR antibody to the cornea to treat T-cell mediated
corneal inflammation, "the Examiner has provided no teaching that the
antibodies are administered at an amount effective to substantially reduce or
substantially inhibit at least one of T-cell differentiation or T-cell cytokine
expression" (Br. 7, 16), nor do the references suggest dosage optimization
by routine experimentation since they do not teach or suggest such
antibodies "could substantially reduce or substantially inhibit at least one of
T-cell differentiation or T-cell cytokine expression," (Id. at 7-8, 16).
Appellants arguments do not persuade us that the "effective amount"
limitation is not taught or suggested by the combination of references relied
on by the Examiner. Neither Appellants' claims, nor the Specification
indicate what amount of anti-C5aR and anti-C3aR antibody is critical to
11
Appeal2014-005917
Application 12/921,308
achieve substantial reduction or substantial inhibition of at least one of T-
cell differentiation or T-cell cytokine expression. As discussed above, the
combination of references suggest administration of anti-C5aR and anti-
C3aR antibodies to the cornea in order to treat T-cell mediated corneal
inflammation. Fung teaches that determination of dosage amounts to effect
such treatment can be accomplished following conventional methods such as
extrapolation from dose-response curves and standard clinical techniques.
(Ans. 7; Fung i-fi-f 126-127.) Moreover, Fung provides that a dosage range
administered to a patient is typically O.lmg/kg to 100 mg/kg of the patient's
body weight. (Fung i-f 128.) There is no evidence that the range taught to be
administered by Fung to treat T-cell mediated ocular diseases would not also
achieve the claimed functional results. Absent evidence to the contrary,
therefore, we conclude the Examiner has set forth a prima facie case that the
effective amount limitation of claim 10 is taught by the combination of
Fung, Jha, and Qazi, and of claim 26 is taught by the combination of Fung,
Jha, Meyers-Elliot, Qazi, and Stuart. In re Swinehart, 439 F.2d 210, 213
( CCP A 1971) ("where the Patent Office has reason to believe that a
functional limitation asserted to be critical for establishing novelty in the
claimed subject matter may, in fact, be an inherent characteristic of the prior
art, it possesses the authority to require the applicant to prove that the
subject matter shown to be in the prior art does not possess the characteristic
relied on.")
Appellants' separate arguments pertaining to Meyers-Elliot and Stuart
are that neither reference provides a rationale that an antibody directed
against C5aR and an antibody directed against C3aR can be administered to
12
Appeal2014-005917
Application 12/921,308
the cornea to inhibit corneal inflammation or complement. (Br. 18, 20.) We
do not find this argument persuasive because Jha provides this suggestion, as
discussed above. We agree with the Examiner that Meyers-Elliot teaches
that in HSV keratitis complement is localized in the cornea of subjects with
stromal infiltrates and that complement pathway components play an
essential role in the development of HSV keratitis. (Final Action 4.) We
also agree with the Examiner that Stuart evidences that HSV keratitis is
T-cell mediated. (Id.) In light of these findings and those discussed above
regarding Fung and Jha, we agree with the Examiner's conclusion that one
of skill in the art would have found it obvious to target HSV keratitis as one
of the ocular diseases in Fung's method of treating ocular diseases with
antibodies directed against C5aR and an antibody directed against C3aR
administered to the cornea.
Claims 1 7 and 29 require that the complement antagonist is "in an
ophthalmic preparation." (Br. 23, 24.) The Examiner explains that Fung
teaches administration by an eye wash solution. (Final Action 3, 4.) We
find no error in the Examiner's finding, and there are no arguments to the
contrary from Appellants. Thus, we affirm the Examiner's obviousness
rejection of claims 17 and 29 for the reasons set forth above ..
SUMMARY
For the reasons discussed, we affirm the Examiner's rejection of
claims 10 and 17 under 35 U.S.C. § 103(a) as being unpatentable over Fung,
Jha, and Qazi. We also affirm the Examiner's rejection of claims 26 and 29
under 35 U.S.C. § 103(a) as being unpatentable over Fung, Jha,
Meyers-Elliot, Qazi, and Stuart. However, because our reasoning differs to
13
Appeal2014-005917
Application 12/921,308
some degree from the Examiner's regarding the presence of both antibodies
directed against C5aR and C3aR in the at least one complement antagonist,
we designate our affirmance of both of these rejections as New Grounds of
Rejection.
TIME PERIOD FOR RESPONSE
This decision contains new grounds of rejection pursuant to 37 C.F.R.
§ 41.50(b). 37 C.F.R. § 41.50(b) provides "[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 grounds 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 prosecution 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 ....
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, 37 C.F.R. § 41.50(b)
14