Ex Parte Simard

Patent Trial and Appeal Board

Dec 10, 2018

15013469 (P.T.A.B. Dec. 10, 2018)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE
15/013,469 02/02/2016
88684 7590 12/12/2018
XBiotech, Inc.
5425 Park Central Court
Suite 111
Naples, FL 34109
FIRST NAMED INVENTOR
John Simard
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.
5407-0244 8433
EXAMINER
DENT, ALANA HARRIS
ART UNIT PAPER NUMBER
1643
NOTIFICATION DATE DELIVERY MODE
12/12/2018 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):
sakptomail@iplawpro.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte JOHN SIMARD
Appeal2017-010206
Application 15/013 ,469
Technology Center 1600
Before JEFFREY N. FREDMAN, ROBERT A. POLLOCK, and
JACQUELINE T. HARLOW, Administrative Patent Judges.
FREDMAN, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal 1,2,3 under 35 U.S.C. § 134 involving claims to a
method of reducing the formation of new metastases by administration of
anti-human IL-1 a antibodies. The Examiner rejected the claims as
anticipated and as obvious. We have jurisdiction under 35 U.S.C. § 6(b).
We affirm.
1 Appellant identifies the Real Party in Interest as XBiotech, Inc. (see Br. 3).
2 We have considered and refer to the Specification of Feb. 2, 2016
("Spec."); Final Office Action of Sept. 8, 2016 ("Final Act."); Appeal Brief
of Jan. 31, 2017 ("Br."); and Examiner's Answer of May 4, 2017 ("Ans.").
3 This appeal is related to Appeal 2013-002616 which affirmed the rejections
in parent application US 12/302,066 (see Br. 4).
Appeal2017-010206
Application 15/013,469
Statement of the Case
Background
"[A]nti-IL-la antibody can inhibit metastatic potential of tumors
through interruption of the physiological role tumor-derived IL- I a plays in
tumor metastasis. Moreover, because IL- I a is expressed by tumors, an
antibody targeting IL- I a can cause direct tumor cytotoxicity through
antibody directed cellular cytotoxicity" (Spec. ,r 6).
The Claims
Claims 1--4 are on appeal. Independent claim 1 is representative and
is reproduced below:
1. A method of reducing the formation of new
metastases comprising human cancer cells in a subject
harboring said human cancer cells, the method comprising a
step of administering to the subject an amount of anti-human
IL- I a antibodies effective to reduce the development of new
metastases in the subject, wherein the formation of new
metastases in the subject is reduced.
Br. 13 (Claims Appendix).
The Issues
A. The Examiner rejected claims 1 and 4 under 35 U.S.C. § I02(b) as
anticipated by Garrone '085 4 (Final Act. 3--4).
B. The Examiner rejected claims 1 and 4 under 35 U.S.C. § I02(b) as
anticipated by Garrone '7665 (Final Act. 6-7).
C. The Examiner rejected claims 1, 3, and 4 under 35 U.S.C. § I02(b) as
anticipated by Witte6 (Final Act. 4--5).
4 Garrone et al., US 5,959,085, issued Sept. 28, 1999.
5 Garrone et al., EP O 659 766 Al, published June 28, 1995.
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D. The Examiner rejected claims 1--4 under 35 U.S.C. § I03(a) as
obvious over Garrone '085, Witte, and Varnum 7 (Final Act. 7-9).
E. The Examiner rejected claims 1--4 under 35 U.S.C. § I03(a) as
obvious over Garrone '766, Witte, and Varnum (Final Act. 10-12).
A. &B. 35 USC§ 102(b) over Garrone '085 and Garrone '766
Because the disclosures of Garrone '085 and Garrone '766 are similar,
if not identical, we will consider these anticipation rejections together.
The Examiner finds that Garrone '085 "discloses human monoclonal
antibodies (HuMabs ), such as IL- I a for the treatment of tumors, see
abstract; and column 11, lines 66 and 67" (Final Act. 4). The Examiner
finds Garrone '766 teaches "human monoclonal antibodies against human
cytokine, human interleukin alpha, see abstract. This antibody may be
useful in tumor treatment, see page 8, last sentence of last full paragraph.
This disclosure reads on treating new metastases because tumors comprise
human cancer cells" (Final Act. 6-7).
The issue with respect to this rejection is: Does the evidence of
record support the Examiner's conclusion that Garrone '085 and Garrone
'766 anticipate claims 1 and 4?
Findings of Fact
1. Garrone '085 teaches that the "HuMAbs and fragments of the
present invention may be used therapeutically to treat existing symptoms
6 Witte et al., US 2003/0026806 Al, published Feb. 6, 2003.
7 Varnum et al., US 2004/0097712 Al, published May 20, 2004.
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Application 15/013,469
associated with the antigen of interest. For example, IL-la" (Garrone '085
11 :26-28; cf Garrone '766 8:34--35).
2. Garrone '085 teaches that "IL- I a has been reported to act as an
autocrine growth stimulator for human thyroid and gastric carcinoma cells
[Ito et al., Cancer Res., 53:4102-4106 (1993)], as well as adult T cell
leukemias [Shirakawa et al., Cancer Res., 49:1143-1147 (1989)]. Thus, an
anti-IL-la HuMAb of the invention may be useful in the treatment of
tumors" (Garrone '085 11:62---67; cf Garrone '766 8:53-56).
3. Garrone '085 teaches "an antibody fragment such as an Fab,
F(ab')2, Fv, single-chain binding protein, or any other binding polypeptide
which contains one or more complementarity determining regions (CDRs)"
(Garrone '085 9:10-14; cf Garrone '766 7:9-11).
4. Garrone '085 exemplifies the "ability of human monoclonal
antibody X3 to inhibit the binding of radio labeled human IL- I a to IL- I
receptors" and finds that "the antibody X3 blocks in a dose-dependent
manner the binding of radio labeled human IL- I a on EL4 cells" ( Garrone
'085 20:38-58; cf Garrone '766 15:51-16:4).
5. Garrone '085 teaches that the "concentration of the HuMAb or
fragment of the invention in the pharmaceutical compositions may vary, e.g.,
from about 0.1 µg/ml to about 1 mg/ml ... The dose will be adjusted in a
conventional manner by the skilled artisan to levels appropriate to achieve
the desired result in vivo" (Garrone '085 12:39-47; cf Garrone '766 9:20-
24).
6. Garrone '085 teaches that "biological activity of human IL-I
was measured by its ability to stimulate IL-2 production by the murine
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thymoma subline EL4-6.1" (Garrone '085 21:25-27; cf Garrone '766
16:25-26).
7. Garrone '085 teaches that the "proliferation of IL-2-dependent
CTLL cells is proportional to the concentration of IL-2 produced by EL4
cells in the first step of culture" (Garrone '085 21:30-33; cf Garrone '766
16:28-29).
8. Garrone '085 teaches that the "human monoclonal antibody X3
specifically inhibits human IL-I a-induced IL-2 production by EL4 cells"
(Garrone '085 21:64---65; cf Garrone '766 16:46-47).
Principles of Law
"The protocol of giving claims their broadest reasonable interpretation
during examination does not include giving claims a legally incorrect
interpretation. This protocol is solely an examination expedient, not a rule
of claim construction." In re Skvorecz, 580 F.3d 1262, 1267 (Fed. Cir.
2009).
Analysis
Appellant contends the "sections of Garrone relied upon for this
rejection do not expressly teach that' ... the formation of new metastases in
the subject is reduced.' ... Accordingly, Garrone fails to expressly teach
claim 1" (Br. 6-7). Appellant also contends Garrone "does not make clear
that administering an anti-IL- I a antibody would inevitably result in the
reduction of the development of new metastases in the subject" (id. at 7).
The Examiner, in response, cites our discussion from the parent
application Appeal 2013-002616, but does not specifically address the
changes in claim 1 relative to the claims at issue in the previous case,
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specifically the addition of the clause "wherein the formation of new
metastases in the subject is reduced."
We therefore begin with claim interpretation. In our Decision in
Appeal 2013-002616, there was no "wherein" clause, but simply a method
of administering a particular dose of anti-human IL-I a antibodies.
The "wherein" clause is reasonably assigned patentable weight
consistent with Griffin, a case where the Federal Circuit addressed a claim to
a "method for diagnosing an increased risk for thrombosis" comprising two
steps of "obtaining" nucleic acids and "assaying" for point mutations and a
final clause "wherein the presence of said point mutation in said test nucleic
acid indicates an increased risk for thrombosis." Griffin v. Bertina, 285 F.3d
1029, 1031 (Fed. Cir. 2002). Griffin found that "the Board did not err in
giving limiting effect to the 'wherein' clauses" because they give "meaning
and purpose to the manipulative steps." Id. at 1033.
Similarly here, the "wherein" clause limits the patient population to
cancer patients who have cancers capable of metastasis, a subset of all
cancer patients. The Examiner provides no specific explicit teaching or
other evidence that either Garrone reference discloses treatment to a limited
subset of cancer patients who are subject to metastasis.
We also agree with Appellant that neither Garrone reference
inherently addresses this limitation regarding the patient population of
cancer patients subject to metastasis. Perricone distinguished inherency
with regard to different patient populations, specifically between the topical
application of a lotion to skin generally to prevent sunburn, and the topical
application of a lotion to treat sunburned skin. Perricone v. Medicis Pharm.
Corp., 432 F.3d 1368, 1378 (Fed. Cir. 2005). In Perricone, when treatment
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was applicable to any person with skin, inherency applied because everyone
had skin, but Perricone found that when the patient population was limited to
patients with sunburn the "issue is not ... whether [ the prior art] lotion if
applied to skin sunburn would inherently treat that damage, but whether [the
prior art] discloses the application of its composition to skin sunburn. It
does not." Id.
The same analysis applies here. There may be a general teaching in
the Garrone references to treat cancer patients with anti-human IL-I a
antibodies, and if those same patients also happened to be at risk of new
metastases, the treatment might also necessarily result in reducing
metastasis, analogous to the skin treatment at issue in Perricone. However,
the Examiner has not established that all cancer patients are at risk of
metastasis. In the same manner that not everyone who applies lotion to their
skin will necessarily have sunburn, not all cancer patients will necessarily be
at risk of new metastases. In re Oelrich, 666 F.2d 578, 581 (C.C.P.A. 1981)
("Inherency, however, 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.").
Conclusion of Law
The evidence of record does not support the Examiner's conclusion
that Garrone '085 and Garrone '766 anticipate claims 1 and 4.
C. 35 USC§ 102(b) over Witte
The Examiner finds "Witte discloses IL- I a monoclonal and
polyclonal antibodies and implementing these IL- I selective binding agents
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in a method of treating IL- I mediated diseases such a tumor metastasis"
(Final Act. 5).
The issue with respect to this rejection is: Does the evidence of
record support the Examiner's conclusion that Witte anticipates claims 1, 3,
and4?
Findings of Fact
9. Witte teaches "humanized, fully human, single chain and/or
bispecific antibodies. Antibody fragments include those portions of an anti-
IL-1 antibody which bind to an epitope on an IL-I polypeptide" (Witt ,r 97).
10. Witte teaches that the "term 'IL-I' means that the text applies
to IL-la or IL-I~" (Witte 48).
11. Witte teaches a "list of acute and chronic IL-1-mediated-
diseases includes but is not limited to the following ... cancer, such as
multiple myeloma and myelogenous (e.g., AML and CML) and other
leukemias, as well as tumor metastasis" (Witte ,r,r 178, 188).
12. Witte teaches that "IL-I antagonist antibodies or antigen
binding domains of the invention are administered in a therapeutically or
prophylactically effective amount to prevent and/or treat loss of bone
associated with metastatic bone disease" (Witt ,r 240).
13. Witte teaches that a "'therapeutically or prophylactically
effective amount' of an IL-I antagonist antibody is that amount which
affects a parameter of an IL- I mediated disease ... Typically, a clinician
will administer the composition until a dosage is reached that achieves the
desired effect" (Witte ,r,r 240-241 ).
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Analysis
Appellant contends "Witte nowhere unequivocally states that tumor
metastasis is a condition associated specifically with elevated IL- I a.
According to Witte' s definitions, tumor metastasis could be only associated
with elevated levels of IL- I a in bodily fluids or tissue, or in the supernatant
of a culture of cells or tissues excised from a subject" (Br. 9). Appellant
further contends Witte "does not make clear that administering an anti-IL-la
antibody would inevitably result in the reduction of the development of new
metastases in the subject, or even that IL- I a is involved in the formation of
new metastases" (id.).
The Examiner responds that the "antibodies of Witte and Appellant
are one and the same, hence the treatment it provides result in the same
therapeutic effect. Products of identical chemical composition cannot have
mutually exclusive properties" (Ans. 8). The Examiner also finds that
"when the species is clearly named, the species claim is anticipated no
matter how many other species are additionally named" (Ans. 8, citing Ex
parte A, 17 USPQ 1716 (BPAI 1990)).
We rely upon our claim interpretation of the "wherein" clause as
discussed above. We agree with the Examiner because Witte specifically
teaches "IL- I antagonist antibodies ... are administered in a therapeutically
or prophylactically effective amount to prevent and/or treat loss of bone
associated with metastatic bone disease" (FF 12). Witte teaches "'IL-I'
means that the text applies to IL- I a or IL- I W' (FF 10). Thus, Witte teaches
administration of antibodies to either of only two different IL- I types, IL- I a
or IL- I~' to patients to prevent or treat sequelae of metastatic bone disease
(FF 10, 12). We think the Examiner reasonably interprets Witte's teaching
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Application 15/013,469
to "prevent" metastatic bone disease as an express teaching to reduce
formation of new metastases.
Regarding inherency, we agree with the Examiner that Witte teaches
treatment of a patient population that inherently are at risk of new metastases
(FF 11-12). Thus, applying the Perricone analysis discussed above, Witte
singles out the patient population at issue in claim 1, patients at risk of new
metastases, and directly suggests treatment of those patients with the same
anti IL- I a antibody composition as that required by claim 1 "to prevent
and/or treat loss of bone associated with metastatic bone disease" (FF 12).
"Using the same composition claimed ... in the same manner claimed ...
naturally results in the same claimed ... benefits." Perricone, 432 F.3d at
1380. We therefore agree with the Examiner that Witte both expressly and
inherently anticipates the rejected claims.
Conclusion of Law
The evidence of record supports the Examiner's conclusion that Witte
anticipates claims 1, 3, and 4.
D.&E. 35 USC§ 103(a) over either Garrone '085 or Garrone '766,
Witte, and Varnum
Because the disclosures of Garrone '085 and Garrone '766 are similar,
if not identical, we will consider these two obviousness rejections together.
The Examiner finds "Garrone ['085] teaches HuMabs, such as IL-la
for the treatment of tumors, see abstract; and column 11, lines 66 and 67.
This disclosure reads on treating new metastases because these malignant
growths comprise human cancer cells" (Final Act. 9). The Examiner
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acknowledges that Garrone '085 does not teach "that are polyclonal and the
cancer affects the breast or prostate" (id.).
The Examiner finds Witte teaches "IL- I polyclonal antibodies and
implementing IL- I selective binding agents in a method of treating IL- I
mediated diseases such a tumor metastasis" (Final Act. 9). The Examiner
finds Varnum teaches "treating IL- I mediated diseases, such as prostate
cancer, breast cancer and other malignancies with metastatic potential" (id.).
The Examiner finds it obvious to "combine the teachings of all the
references to manufacture IL- I a polyclonal antibodies and treat breast or
prostate metastatic cancer with all types of antibodies cited herein" (id.).
The issue with respect to this rejection is: Does the evidence of
record support the Examiner's conclusion that Garrone '085 and Garrone
'7 66, along with Witte and Varnum render claims 1--4 obvious?
Findings of Fact
14. Varnum teaches that
anti-IL- I RI antibodies, alone or in combination with other
cytokine inhibitors or other active agents as described above,
can be used to treat various forms of cancer, including acute
myelogenous leukemia, chronic myelogenous leukemia
leukemia, Epstein-Barr virus-positive nasopharyngeal
carcinoma, glioma, colon, stomach, prostate, renal cell,
cervical and ovarian cancers, lung cancer (SCLC and
NSCLC), including cancer-associated cachexia, fatigue,
asthenia, paraneoplastic syndrome of cachexia and
hypercalcemia. Solid tumors, including sarcoma,
osteosarcoma, and carcinoma, such as adenocarcinoma ( for
example, breast cancer) and squamous cell carcinoma are
also treatable. Additional treatable cancers include
esophogeal cancer, gastric cancer, gall bladder carcinoma,
leukemia, including acute myelogenous leukemia, chronic
myelogenous leukemia, myeloid leukemia, chronic or acute
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lymphoblastic leukemia and hairy cell leukemia. Other
malignancies with invasive metastatic potential, including
multiple myeloma, can be treated with the subject
compounds, compositions and combination therapies.
(Varnum ,r 240).
15. Varnum teaches the "combination of an IL- I receptor antibody
and RANKL inhibitors ... is useful for ... anti-tumor therapy aimed at
preventing metastasis to bone" (Varnum ,r 230).
Principles of Law
[D]uring patent prosecution, an examiner is entitled to
reject claims as anticipated by a prior art publication or
patent without conducting an inquiry into whether or not that
prior art reference is enabling. As long as an examiner
makes a proper prima facie case of anticipation by giving
adequate notice under§ 132, the burden shifts to the
applicant to submit rebuttal evidence of nonenablement.
In re Antor Media Corp., 689 F.3d 1282, 1289 (Fed. Cir. 2012). However,
"[o]nce an applicant makes a non-frivolous argument that cited prior art is
not enabling[], the examiner must address that challenge." In re Morsa, 713
F.3d 104, 110 (Fed. Cir. 2013).
Analysis
We adopt the Examiner's findings of fact and reasoning regarding the
scope and content of the prior art (Final Act. 7-12; FF 1-15) and agree that
the claims are obvious over Garrone, Witte, and Varnum. We address
Appellant's arguments below.
Appellant contends "the examiner does not clearly state the
differences between Witte and Varnum over claims 1-4, nor does it clearly
resolve the level of ordinary skill in the pertinent art" (Br. 12).
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We do not find these arguments persuasive because the Examiner
specifically identifies the portions of the cited prior art relied upon and
explains why the claims would have been obvious, moreover, Appellant fails
to explain how the level of ordinary skill in the art should be resolved or
how such resolution would affect the outcome of this inquiry. (see Final Act
7-12).
Appellant contends
Varnum also fails to expressly or inherently teach that anti- IL-
I a antibodies can be used to reduce the formation of new
metastases. Varnum paragraph [0240] relates to anti-IL-
lRlantibodies - not anti-IL-la antibodies. And like Garonne
and Witte, Varnum does not describe any actual experiments
that would have suggested to the skilled artisan that anti- IL- I a
antibodies could actually be used to reduce the formation of
new metastases.
(Br. 10).
We find this argument unpersuasive because a "specification need not
contain a working example if the invention is otherwise disclosed in such a
manner that one skilled in the art will be able to practice it without an undue
amount of experimentation." In re Borkowski, 422 F.2d 904, 908 (CCPA
1970). Here, the prior art evidences that the method may be performed
without undue experimentation, and no evidence is presented in rebuttal.
Specifically, Witte evidences that IL- I mediates tumor metastasis (FF 11 ),
and that IL- I antagonist antibodies are useful in prevention and treatment of
metastatic bone disease (FF 12). Witte specifically teaches dosages for
treatment (FF 13) and anti-IL-I a antibodies (FF 9-10).
In addition, Varnum supports Witte by suggesting that anti-IL-la
antibodies are useful in treatment of "malignancies with invasive metastatic
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potential" (FF 14) and that the "combination of an IL- I receptor antibody
and RANKL inhibitors ... is useful for ... anti-tumor therapy aimed at
preventing metastasis to bone" (FF 15). Thus, Witte and Varnum both
suggest treatment and prevention of metastases using anti-IL- I a antibodies
(FF 9--15). Moreover, Garrone provides examples showing the efficacy of
the human anti-IL-la antibody in vitro (FF 4, 6-8), demonstrates the
expected association with human cancers for the antibody (FF 2), and
provides human dosing information (FF 5).
Therefore, we agree with the Examiner that the ordinary artisan,
informed by Garrone, Witte and Varnum of anti-IL- I a antibodies, including
Garrone's evidence that these antibodies have biological activity (FF 4, 6),
would provide the ordinary artisan with a reasonable expectation of success
in reducing metastases formation. "Obviousness does not require absolute
predictability of success ... all that is required is a reasonable expectation
of success." In re Kubin, 561 F.3d 1351, 1360 (Fed. Cir. 2009) (citing In re
O'Farrell, 853 F.2d 894, 903-904 (Fed. Cir. 1988)). Moreover, the explicit
guidance to prevent metastases (FF 12, 15) using anti-IL-la antibodies (FF
2, 10) demonstrates that the "prior art gives direction as to what parameters
are critical and which of many possible choices may be successful."
0 'Farrell, 853 F.2d at 894.
Conclusion of Law
The evidence of record supports the Examiner's conclusion that
Garrone '085 and Garrone '766, along with Witte and Varnum render claims
1--4 obvious.
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SUMMARY
In summary, we reverse the rejection of claims 1 and 4 under 35
U.S.C. § 102(b) as anticipated by Garrone '085.
We reverse the rejection of claims 1 and 4 under 35 U.S.C. § 102(b)
as anticipated by Garrone '7 66.
We affirm the rejection of claims 1, 3, and 4 under 35 U.S.C. § 102(b)
as anticipated by Witte.
We affirm the rejection of claims 1--4 under 35 U.S.C. § 103(a) as
obvious over Garrone '085, Witte, and Varnum.
We affirm the rejection of claims 1--4 under 35 U.S.C. § 103(a) as
obvious over Garrone '766, Witte, and Varnum.
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
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