Steven Norman. Quayle et al.

Patent Trials and Appeals Board

Sep 26, 2019

14508072 - (D) (P.T.A.B. Sep. 26, 2019)

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.
14/508,072 10/07/2014 Steven Norman Quayle 561948: ACT-011US 7857
12779 7590 09/26/2019
Lathrop Gage LLP
28 State Street
7th Floor
Boston, MA 02109
EXAMINER
RODRIGUEZ, RAYNA B
ART UNIT PAPER NUMBER
1628
NOTIFICATION DATE DELIVERY MODE
09/26/2019 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):
bostonpatent@lathropgage.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
__________

Ex parte STEVEN NORMAN QUAYLE, SIMON STEWART JONES,
KENNETH C. ANDERSON, and TERU HIDESHIMA
__________

Appeal 2019-002354
Application 14/508,0721
Technology Center 1600
__________

Before DONALD E. ADAMS, RICHARD M. LEBOVITZ, 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 a method
treating multiple myeloma, which have been rejected as anticipated or
obvious. We have jurisdiction under 35 U.S.C. § 6(b).
We affirm.
STATEMENT OF THE CASE
Lenalidomide and pomalidomide are immunomodulatory (IMiD)
drugs that “have demonstrated significant clinical activity in multiple
myeloma [(“MM”)] patients.” (Spec. 1.) Appellant’s Specification states

1 We use the word “Appellant” to refer to “applicant” as defined in 37
C.F.R. § 1.42. Appellant identifies the real party in interest as Acetylon
Pharmaceuticals, Inc. and Dana-Farber Cancer Institute. (Br. 3.)
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that “[h]istone deacetylase (HDAC) enzymes represent attractive therapeutic
targets in multiple myeloma, but unfortunately non-selective HDAC
inhibitors have led to dose-limiting toxicities in patients.” (Id.) Appellant’s
invention is directed to combination therapy for MM patients of a histone
deacetylase 6 (HDAC6) specific inhibitor and either lenalidomide or
pomalidomide.
Claims 50, 52, and 61–65 are on appeal. Claim 1 is representative and
reads as follows:
50. A method for treating multiple myeloma in a subject in
need thereof comprising administering to the subject a
therapeutically effective amount of a pharmaceutical
combination comprising an HDAC inhibitor having the
structure:

or a pharmaceutically acceptable salt thereof;
and an immunomodulatory drug selected from
, or a pharmaceutically acceptable
salt thereof, and
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, or a pharmaceutically acceptable
salt thereof.

(Br. 15.)

The following grounds of rejection by the Examiner are before us on
review:
Claims 50, 52, 62, 63, and 65 under 35 U.S.C. § 102(a)(2) as
anticipated by Raje.2
Claim 64 under 35 U.S.C. § 103 as unpatentable over Raje.
Claim 61 under 35 U.S.C. § 103 as unpatentable over Raje and
Zeldis.3
DISCUSSION
Anticipation
The Examiner finds that Raje teaches a method of treating osteolytic
bone lesions associated with multiple myeloma. (Final Action 6.) The
Examiner explains that a patient cannot suffer from such bone lesions
without also having multiple myeloma. (Ans. 14.)
The Examiner finds that a treatment disclosed by Raje is
administration of compound C, the carboxamide depicted below

2 Raje, WO 2013/013113 A2, published Jan. 24, 2013.
3 Zeldis, US 2008/0317708 A1, published Dec. 25, 2008.
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, which is a
compound of formula I, in a therapeutically effective amount. (Final Action
6; Ans. 10.) The Examiner explains that compound C of Raje is the claimed
compound. (Id.)
The Examiner also finds that Raje teaches a method of treating a bone
disorder associated with abnormally high bone catabolism, such as primary
tumor cell involvement in multiple myeloma. (Final Action 6.) The
Examiner explains that Raje teaches the method involves administering a
compound of formula I, as well as administering pomalidomide. (Id.) The
Examiner acknowledges that Raje broadly teaches the use of compounds of
formula that are HDAC6 inhibitors for treating bone disorders, but that it
“exemplifies Compound C as one of 3 specific embodiments of the disclosed
HDAC6 inhibitors of formula (1) . . . for use in treating primary tumor cell
involvement in MM . . . and exemplify pomalidomide as one of 4
compounds which can be administered in combination with the HDAC6
inhibitor.” (Ans. 10.) In light of the foregoing, the Examiner contends that,
even though Raje is silent regarding “treating multiple myeloma” such
would be the inevitable result of administering the same claimed compounds
to the same claimed “subjects (patients suffering from osteolytic bone
lesions associated with multiple myeloma, which are a subset of patients
suffering from MM).” (Final Action 7.)
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We agree with the Examiner’s findings and conclusion of anticipation.
Claimed subject matter is anticipated when every element and limitation of
the claim was previously described in a single prior art reference, either
expressly or inherently, so as to place a person of ordinary skill in
possession of the invention. See Schering Corp. v. Geneva Pharms.,
Inc., 339 F.3d 1373, 1379 (Fed. Cir. 2003). “[The] reference must clearly
and unequivocally disclose the claimed [invention] or direct those skilled in
the art to the [invention] without any need for picking, choosing, and
combining various disclosures not directly related to each other by the
teachings of the cited reference.” In re Arkley, 455 F.2d 586, 587 (CCPA
1972) (emphasis added). We find the various disclosures relied on by the
Examiner to be disclosures that are directly related to each other for the
reasons that follow.
Raje discloses “methods for treating disorders associated with
excessive bone catabolism (resorption), whether as a result of excessive
OCL[4] activity, reduced OBL[5] activity, or both” where the disorder can be
“primary tumor cell involvement in multiple myeloma.” (Raje 7, 9.) Raje
explains that “[m]ultiple myeloma (MM) is a plasma cell malignancy
characterized by a high capacity to induce osteolytic bone lesions” and that
“70–80% of [MM] patients develop osteolytic bone lesions.” (Raje 12.)
Thus, we understand Raje to teach that osteolytic bone lesions in MM
patients are a result of primary tumor cell involvement in MM.6

4 OCL is short for osteoclast. Raje 7.
5 OBL is short for osteoblast. Id.
6 We note that Raje also describe osteosclerotic lesions can be a result of
metastatic bone disease in advanced-stage cancer. (Raje 12.)
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Raje further explains that “[t]he methods described herein include the
administration of effective amounts of HDAC6-selective inhibitors” that are
reverse amide compounds of formula I, such as Compound C. (Id. at 14–15,
62.) Compound C is the claimed compound depicted below.

Raje teaches in particular: “In another embodiment, provided herein is
a method of treating osteolytic bone lesions associated with MM in a subject
in need thereof, comprising administering to the subject a therapeutically
effective amount of Compound C.” (Id. at 62.) Raje also teaches
combination therapy “to improve treatment efficacy” “for the treatment or
reducing risk of” bone lesions associated with MM with a reverse amide
HDAC6 inhibitor of formula I where the additional active agent may be
pomalidomide or lenalidomide. (Id. at 65–66.) While Raje specifically
points to Compound A (id.) as one particular example of an HDAC6
inhibitor of formula I for such use, we do not find that disclosure to be one
that excludes the other formula I compounds described. That is because
Raje states that the combination therapy in which “the administration of
additional active agents to improve treatment efficacy” is in combination
with “a reverse amide HDAC6 inhibitor as described herein.” (Id.) And as
discussed above, Compound C is specifically identified as a reverse amide
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HDAC6 inhibitor to administer for treating osteolytic bone lesions
associated with MM. (Id. at 62.)
Furthermore, while Raje indicates pomalidomide and lenalidomide as
active agents for combination therapy in a list of nine active agents, we
conclude that the disclosure is sufficient for anticipation. Perricone v.
Medicis Pharmaceutical Corporation, 432 F.3d 1368 (Fed. Cir. 2005) (“In
total, Pereira teaches a total of fourteen skin benefit ingredients. This court
rejects the notion that one of these ingredients cannot anticipate because it
appears without special emphasis in a longer list.”)
For the foregoing reasons, we disagree with Appellant that Raje “does
not clearly and unequivocally disclose the claimed method” (Br. 6–9).
Appellant further argues that “the Examiner has not properly
established that the method of treating bone disease disclosed in Raje could
necessarily be effective for treating the general disease of multiple myeloma
in a subject in need thereof.” (Id. at 9–10.) We do not find this argument
persuasive. As discussed above, and articulated by the Examiner, Raje
discloses combination therapy for treating osteolytic bone lesions associated
with MM. We agree with the Examiner that a patient with osteolytic bone
lesions associated with MM necessarily has MM. (Ans. 14.) Appellant does
not dispute the foregoing. Furthermore, in treating the bone lesions induced
by MM, the therapy with Compound C would necessarily treat an element of
MM in the patient, namely the MM induced bone lesions. Moreover, Raje
discloses that known MM therapies include use of immunomodulatory
drugs, and lenalidomide and pomalidomide are immunomodulatory drugs
that Raje discloses to use in conjunction with a reverse amide HDAC6
inhibitor (Raje 65) described for treating with osteolytic bone lesions
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associated with MM, such as Compound C (Raje 62). Consequently, the
combination therapy taught by Raje that includes administration of
pomalidomide would inherently treat MM. We agree with the Examiner,
that whether or not specifically identified by Raje, the treatment method
disclosed for treating patients with osteolytic bone lesions associated with
MM, a subset of patients with MM, would necessarily result in treating MM
via both the immunomodulatory drug which is known to treat MM, as well
as Compound C which is described to treat osteolytic bone lesions that are a
result of MM, because the patient population is the same as the claimed
population. (Ans. 14–15); Cf. Perricone, 432 F.3d 1376–79 (finding claims
directed to a method for treating skin sunburn comprising topically applying
to the skin sunburn not to be anticipated by a prior art reference that taught a
cosmetic composition for topical application to skin because “[s]kin sunburn
is not analogous to skin surfaces generally” and the prior art reference “does
not disclose topical application to skin sunburn,” and “is silent about any
sunburn prevention or treatment benefits”).)
Thus, for the foregoing reasons, we affirm the Examiner’s rejection of
claim 50 as being anticipated by Raje.
Claims 52, 62, 63, and 65 have not been argued separately and
therefore fall with claim 50. 37 C.F.R. § 41.37(c)(1)(iv).
II
Obviousness of claim 64
Claim 50 requires administration of “a pharmaceutical combination”
comprising the HDAC inhibitor having the following structure
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and one of either lenalidomide or pomalidomide. Claim 64 requires that the
HDAC inhibitor and IMiD drug of the pharmaceutical combination are
administered at different times.
Claim 64 depends from claim 50 and further recites “wherein the
HDAC inhibitor and the immunomodulatory drug are administered at
different times.” The Examiner notes that Raje does not specifically teach
administering the HDAC inhibitor and the immunomodulatory drug at
different times in the method of treating osteolytic bone lesions associated
with MM in a subject in need thereof. (Final Action 14.) However, the
Examiner finds that Raje does “teach in some embodiments, these additional
agents [i.e., the second agent in the combination therapy,] can be
administered substantially concurrently with (e.g. in separate or the same
dose form) or can be administered concurrently.” (Id.) Thus, the Examiner
finds that it would have been obvious to one of ordinary skill in the art with
a reasonable expectation of success to carry out the combination therapy
treating osteolytic bone lesions associated with MM taught by Raje by
administering separate dose forms at different times based on the therapeutic
needs of the patient. (Id.)
We agree with the Examiner’s findings and conclusion of
obviousness.
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Raje states, when describing combination therapies, such as “for the
treatment or reducing risk of a condition described herein, e.g., bone loss,
e.g., bone lesions associated with multiple myeloma”. . . “[i]n some
embodiments, these additional agents can be administered substantially
concurrently with (e.g., in separate or the same dose form) or can be
administered concurrently.” (Spec. 65–66.) In other words, Raje does not
indicate that combination therapy is only effective with administration of the
active agents at the same time and in the same dose form. Rather, the
therapy can involve administering separate dose forms of the drugs
“substantially” concurrently with, i.e., each therapeutic does not have to be
administered at the same time. Thus, we agree with the Examiner that it
would have been obvious to one of ordinary skill in the art to administer
compound C and pomalidomide in combination therapy to treat bone lesions
associated with MM at different times with a reasonable expectation of
success.
Appellant argues that “Raje provides no motivation to one of skill in
the art to arrive at the combinations specified in instant claim 50” and thus
concludes that claim 64 is also not obvious. (Br. 10.) As noted above, we
agree with the Examiner that Raje anticipates claim 50. Thus, we do not
find this argument as to the non-obviousness of claim 50, and the consequent
non-obviousness of claim 64, persuasive.
Appellant further argues that “the claimed methods embody
unexpected results.” (Id.) It is well established that evidence of unexpected
results may not overcome a rejection based on anticipation. See, e.g., In re
Malagari, 499 F.2d 1297, 1302 (CCPA 1974) (“If the rejection under § 102
is proper . . . appellant cannot overcome it by showing such unexpected
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results or teaching away in the art, which are relevant only to an obviousness
rejection.”). Thus, Appellant’s argument as it pertains to claim 50, which is
anticipated by Raje, is not persuasive.
Moreover, as to claim 64, “[i]t is well established that the objective
evidence of nonobviousness must be commensurate in scope with the
claims.” In re Lindner, 457 F.2d 506, 508 (CCPA 1972); In re Peterson,
315 F.3d 1325, 1330–31 (Fed. Cir. 2003). Claim 64 requires the HDAC
inhibitor and the immunomodulatory drug to be administered at different
times. As the Examiner explains, the evidence relied upon by Appellant (Br.
11 (pointing to Example 14 of the Specification)), does not indicate that the
claimed HDAC and the immunomodulatory drug are administered at
different times. Thus, the evidence Appellant points to for unexpected
results is not commensurate in scope with claim 64 and is not persuasive of
nonobviousness.
Therefore, for the foregoing reasons, we affirm the Examiner’s
rejection of claim 64 as being obvious over Raje.

Obviousness of claim 61
Claim 61 depends from claim 50, and further recites “the subject was
previously refractory to an immunomodulatory drug.” The Examiner finds
that Zeldis teaches a method of treating MM comprising administering
pomalidomide and a therapeutically effective amount of a second agent to a
patient that is refractory to conventional therapy including refractory to an
immunomodulatory drug. (Final Action 14–15, 17.) The Examiner explains
that “Zeldis teaches the cancer is refractory or resistant to chemotherapy or
radiation; in particular refractory to thalidomide [0102].” (Id. at 17; Ans.
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19.) The Examiner notes that “[t]halidomide reads on an
immunomodulatory drug as evidenced by the instant [S]pecification which
teaches the IMiD is preferably thalidomide (see page 25, lines 10-12).” (Id.)
The Examiner concludes that in light of Zeldis’ teachings, it would have
been obvious to one of ordinary skill in the art with a reasonable expectation
of success to use the treatment of Raje, i.e., administration of compound C
and pomalidomide to treat a bone disorder associated with primary tumor
involvement in MM in a subject in need thereof, where the MM is refractory
to an immunomodulatory drug. (Final Action 15, 17; Ans. 19.)
Appellant argues that Zeldis teaches immunomodulatory agents for
the treatment of MM which is relapsed, refractory, or resistant to
conventional therapy, where conventional therapies are described as
“‘surgery, chemotherapy, radiation therapy, hormonal therapy, biological
therapy, and immunotherapy’ and other non-drug type therapies.” (Br. 12.)
Thus, argues Appellant, “Zeldis teaches treatment of cancers that are
refractive to conventional therapies using immunomodulatory agents, and
does not teach treatment of cancers that are refractory to immunomodulatory
agents as specified in the instant claims” and the reference does not render
obvious claim 61. (Id. at 13.) We do not find Appellant’s argument
persuasive.
We agree with the Examiner that Zeldis teaches MM treatment using
pomalidomide where the cancer is refractory to thalidomide, an
immunomodulatory drug. There is no dispute that thalidomide is an
immunomodulatory drug. (See Spec. 25:19–20.) Zeldis states:
In another embodiment, the cancer is refractory or resistance to
chemotherapy or radiation; in particular, refractory to
thalidomide.
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(Zeldis ¶ 102.) In short, Zeldis equates treatment with thalidomide to
“chemotherapy or radiation.” And, Zeldis teaches these treatments are
examples of therapies conventionally used to treat, prevent or manage
cancer. (Id. ¶ 18.)
Thus, not only does Zeldis teach treating cancer that is refractory to
prior treatment with an immunomodulatory agent (Br. 12), it also explicitly
teaches, as the Examiner pointed out in the Answer to which Appellant does
not respond, that the cancer to be so treated may be refractory to
thalidomide, an undisputedly immunomodulatory agent (Ans. 19).
Thus, for the foregoing reasons, we affirm the Examiner’s rejection of
claim 61 as being obvious over Raje and Zeldis.
SUMMARY
In summary:
Claims
Rejected
Basis  Affirmed Reversed
50, 52, 62, 63, 65 § 102(a)(2) Raje  50, 52, 62, 63,
65

64 § 103 Raje  64
61 § 103 Raje and
Zeldis
61
Overall Outcome 50, 52, and
61–65

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TIME PERIOD FOR RESPONSE
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