Ex Parte Riggs-Sauthier et al

Patent Trial and Appeal Board

Aug 1, 2018

14122384 (P.T.A.B. Aug. 1, 2018)

UNITED STA TES p A TENT AND TRADEMARK OFFICE
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR
14/122,384 11/26/2013 Jennifer Riggs-Sauthier
21968 7590 08/02/2018
NEKT AR THERAPEUTICS
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
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ART UNIT PAPER NUMBER
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MAIL DATE DELIVERY MODE
08/02/2018 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 PATENT TRIAL AND APPEAL BOARD
Ex parte JENNIFER RIGGS-SAUTHIER,
DEBORAH H. CHARYCH, CLARK NORMAN EID, DENNIS G. FRY,
MARINA KONAKOV A, and CHRISTINE FRANCES LOEHRLEIN
Appeal2017-008013 1
Application 14/122,384
Technology Center 1600
Before FRANCISCO C. PRATS, JEFFREYN. FREDMAN, and
JOHN E. SCHNEIDER, Administrative Patent Judges.
PRATS, Administrative Patent Judge.
DECISION ON APPEAL
This appeal under 35 U.S.C. § 134(a) involves claims to a compound
that has an affibody conjugated to a docetaxel residue. The Examiner
rejected the claims for obviousness.
We have jurisdiction under 35 U.S.C. § 6(b)(l).
We affirm.
STATEMENT OF THE CASE
The sole rejection before us for review is the Examiner's rejection of
claims 2, 5, 23, and 29-33, under 35 U.S.C. § 103(a) for obviousness over
1 Appellants state that the real party in interest is Nektar Therapeutics. Br. 3.
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Application 14/122,384
Breitenkamp, 2 Ahlgren, 3 Veronese, 4 and Crown. 5 Ans. 2-7.
Br. 8.
Claim 2 is representative and reads as follows:
2. A compound, according to the structure:
wherein:
n is an integer from 2 to 4000; and
Dr is a residue of docetaxel.
DISCUSSION
The Examiner's Prima Facie Case
In determining that the compound recited in representative claim 2
would have been obvious, the Examiner cited Breitenkamp as disclosing a
polyethylene glycol-based (PEG) bifunctional compound having the same
core structure as recited in claim 2. Ans. 2-3. The Examiner found that
Breitenkamp also disclosed that one end of the bifunctional compound could
include a linked small molecule drug such as a taxane, for example
2 US 2008/0207913 Al (published Aug. 28, 2008).
3 Sara Ahlgren et al., Targeting of HER2-Expressing Tumors with a Site-
Specifically 99mTc-Labeled Recombinat Affibody Molecule, ZHER2:2395, with C-
Terminally Engineered Cysteine, 50 J. Nucl. Med. 781-789 (2009)
(hereinafter "Ahlgren").
4 Francesco M. Veronese, Peptide and protein PEGylation: a review of
problems and solutions, 22 Biomaterials 405--417 (2001 ).
5 John Crown et al., Docetaxel and Paclitaxel in the Treatment of Breast
Cancer: A Review of Clinical Experience, 9 The Oncologist 24--32 (2004)
(hereinafter "Crown").
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Application 14/122,384
paclitaxel, and the other end of the compound could include a linked
targeting group. Id. at 3-5.
The Examiner found that Breitenkamp' s compound differed from the
compound recited in Appellants' claim 2 in that "Breitenkamp et al. do not
teach: 1) linking an affibody to the maleimide group; and 2) docetaxel." Id.
at 5.
As evidence that an ordinary artisan nonetheless would have
considered the compound of Appellants' claim 2 obvious, the Examiner
cited Ahlgren as disclosing an affibody that binds specifically to breast
cancer tumors, and cited Veronese as evidence that it would have been
obvious to conjugate the C-terminal cysteine residue of Ahlgren's affibody
to the maleimide residue of Breitenkamp's bifunctional compound. Id. at 5-
6.
As evidence that it would have been obvious to link a docetaxel
residue to the other end of Breitenkamp' s bifunctional compound, the
Examiner cited Crown to show that docetaxel was known in the art as a
breast cancer treating agent similar in activity to paclitaxel. Id. at 6.
Based on the references' combined teachings, the Examiner reasoned
that it would have been obvious to attach Ahlgren's breast cancer-binding
affibody to Breitenkamp' s paclitaxel-containing conjugate "because Ahlgren
et al. teach that breast is the type of cancer for which HER2 imaging
primarily will have a clinical application and further because Breitenkamp et
al. teach that targeting groups ( e.g. affibodies) can be attached to the other
end of the PEG." Id.
Furthermore, the Examiner reasoned, "one of ordinary skill in the art
would have been motivated to substitute a taxane used for the treatment of
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breast cancer (i.e. paclitaxel) for another taxane used for the treatment of
breast cancer (i.e. docetaxel), see MPEP [§] 2144.06." Id.
Analysis
As stated in In re Oetiker, 977 F.2d 1443, 1445 (Fed. Cir. 1992):
[T]he examiner bears the initial burden ... of presenting a
primafacie case ofunpatentability ....
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 the present case, having carefully considered the arguments and
evidence advanced by Appellants and the Examiner, Appellants do not
persuade us that the preponderance of the evidence fails to support the
Examiner's conclusion of obviousness as to claim 2. To the contrary, we
adopt as our own the Examiner's findings of fact as to the cited prior art, as
well as the conclusion of obviousness based thereon. We add the following
discussion of Appellants' arguments for emphasis.
As to the Examiner's prima facie case, Appellants do not persuade us
that the Examiner has "not provided any reasoning why one of skill in the art
would specifically select any of the 71 specific, and 49 classes of, small
molecule drugs for use in the bi-functional linkers of Breitenkamp." Br. 6.
Breitenkamp describes "bifunctional polymers, methods of preparing
the same, and intermediates thereto. These compounds are useful in a
variety of applications including the PEGylation of biologically active
molecules." Breitenkamp, abstract.
As the Examiner found, and Appellants do not dispute, Breitenkamp' s
compounds have a general formula encompassed by Appellants' claim 2 (id.
,r,r 5-11 ), and Breitenkamp exemplifies a compound within its general
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formula that has the same core structure as the compound recited in
Appellants' claim 2 (id. ,r 306 (Example 30)).
Breitenkamp explains that its bifunctional PEG compounds can have a
"small molecule drug" at one end of the compound, and a "targeting group"
at the other end of the compound (id. ,r 212), the targeting group providing
"targeted delivery" (id. ,r 214) of the conjugated drug.
It might be true, as Appellants contend (Br. 6), that Breitenkamp
discloses 71 specific, and 49 classes of, small molecule drugs for use in its
compounds, and does not exemplify linking paclitaxel to its compounds.
Breitenkamp, nonetheless, expressly discloses that taxanes in general, and
paclitaxel in particular, are suitably linked to its bifunctional compounds:
One of ordinary skill in the art would recognize that the
present compounds are useful for the PEGylation of small
molecule drugs. Small molecule drugs suitable for PEGylation
with the present compounds include, but are not limited to,
those having a functional group suitable for covalently linking
to the bifunctional PEG's of the present invention. Such drugs
include, without limitation, chemotherapeutic agents or other
anti-proliferative agents including taxanes (Taxol and taxotere
derivatives), ... spindle poisons (Vinblastine, Vincristine,
Vinorelbine, Paclitaxel) ....
Id. ,r 216 ( emphasis added).
That taxanes and paclitaxel are among a larger group of drugs suitable
for attachment to Breitenkamp' s compounds, does not negate Breitenkamp' s
express disclosure that taxanes and paclitaxel are suitably linked to its
bifunctional compounds. See Merck & Co. v. Biocraft Labs., Inc., 87 4 F .2d
804, 807 (Fed. Cir. 1989) (species claim held obvious where it recited one of
1200 possible combinations of embodiments disclosed by reference and
where reference suggested no preference for claimed embodiment).
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Breitenkamp might not expressly disclose attaching the docetaxel of
Appellants' claim 2 to its bifunctional compound. Crown, however,
discloses that not only was docetaxel a known taxane recognized as being
similarly useful to paclitaxel for treating breast cancer, certain practitioners
preferred docetaxel for breast cancer treatment. See Crown 24 ("In the 10
years since their initial licensing in Europe, the taxanes, paclitaxel and
docetaxel, have emerged as fundamental drugs in the treatment of breast
cancer.") (Abstract); see also id. ("At the current time, the pharmacokinetic
profile, consistent positive clinical results, and convenience of an
intermittent, short-infusion schedule have made docetaxel the preferred
taxane for many clinicians treating patients with breast cancer.").
Thus, on the current record, Breitenkamp teaches that taxanes in
general, and paclitaxel in particular, were among the drugs suitable for
targeted delivery using its bifunctional compounds, and Crown teaches that
docetaxel was a known taxane similarly useful to paclitaxel for treating
breast cancer. And, Crown further teaches that some practitioners preferred
docetaxel for breast cancer treatment. Appellants, therefore, do not persuade
us that the evidence of record fails to support the Examiner's finding that an
ordinary artisan had a good reason for, and a reasonable expectation of
success in, using docetaxel as the small drug molecule attached to
Breitenkamp' s bifunctional compounds.
As to the "targeting group" attached to the other end of Breitenkamp' s
bifunctional compounds (Breitenkamp ,r,r 212, 214 ), it might be true, as
Appellants contend, that Breitenkamp discloses "10 specific, and 10 classes
of, other targeting groups," none of which is an affibody. Br. 6.
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As noted above, however, Breitenkamp discloses that the targeting
group of its compounds provides "targeted delivery" (Breitenkamp ,r 214) of
the conjugated drug. And as also noted above, Breitenkamp discloses that
taxanes in general, and paclitaxel in particular, were useful drugs deliverable
by using its compounds (id. ,r 216).
Given that taxanes, such as docetaxel and paclitaxel, were known in
the art to be useful for treating breast cancer (see Crown 24), Appellants do
not persuade us that the Examiner erred finding that an ordinary artisan had
good reason to use a targeting group directed to breast cancer when using a
taxane as the delivered small molecule drug. And, given Ahlgren's
disclosure that its affibody was useful for targeting the label 99mTc to tumors
expressing a breast-cancer specific antigen (see Ahlgren 781 ), Appellants do
not persuade us that the Examiner erred in finding that an ordinary artisan
had good reason for, and a reasonable expectation of success in, using
Ahlgren's affibody as the targeting group of Breitenkamp's compound, in
order to target taxanes, such as docetaxel, to breast cancer tumors.
In sum, given the discussed teachings in the cited references,
Appellants do not persuade us that the Examiner erred in finding that the
references' combined suggest the compound recited in claim 2. Although
we acknowledge that the obviousness of a chemical compound "'can be
proved"' through the lead compound analysis (Br. 6 (quoting Eisai Co. Ltd.
v. Dr. Reddy 's Labs., Ltd, 533 F.3d 1353, 1357 (Fed. Cir. 2008) (emphasis
added)), Appellants identify no legal authority suggesting that a rigid lead
compound analysis must be employed in every instance in which the
obviousness of a chemical compound is at issue.
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In any event, as discussed above, the Examiner identified a compound
in Breitenkamp described as being useful for targeted drug delivery, the
compound having the same core structure as the compound recited in
Appellants' claim 2. And, as also discussed above, the Examiner explained
why an ordinary artisan would have found it obvious to modify that
compound to have the functional groups (docetaxel and an affibody) at the
locations required by claim 2. Appellants, therefore, do not persuade us that
the evidence of record fails to support the Examiner's prima facie case as to
claim 2.
Turning to the objective evidence of nonobviousness advanced by
Appellants, Appellants do not persuade us (see Br. 5) that the Examiner
failed to consider the disclosures in Examples 7-11 of Appellants'
Specification. To the contrary, in the Final Action from which this appeal
was taken, the Examiner stated expressly that those examples had been
considered:
With respect to Applicants' arguments regarding the
Office not having considered the objective evidence of non-
obviousness provided in Examples 7-11 of the application, it is
noted that Applicants have not presented any evidence of
commercial success, long-felt but unsolved needs, failure of
others, and unexpected results (see MPEP [§] 2141).
Final Act. 9.
In that regard, we acknowledge the results and data in Appellants'
Specification as to the disclosed conjugates' stability in tissue culture growth
medium (Spec. ,r,r 234--235 and Table 4 (Example 7)), the conjugates'
plasma stability (Spec. ,r,r 236-240 and Table 5 (Example 8)), the
conjugates' in vitro cytotoxicity (Spec. ,r 241, Table 6, and Figs. 4--6
(Example 9)), the conjugates' pharmacokinetic profiles (Spec. ,r,r 242-244,
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Table 7, and Fig. 7 (Example 10)), and the conjugates' antitumor activity as
compared to free docetaxel (Spec. ,r,r 245-255, Table 8, and Figs. 8-11
(Example 11 )).
Appellants, however, do not identify any specific assertion or
statement in the Specification suggesting that, or explaining why, the
disclosed results would have been unexpected. Rather, the sole statements
of record that the disclosed results would have been unexpected are the
assertions in the Appeal Brief. See Br. 5, 7. It is well settled that, in the
absence of objective supporting evidence showing that disclosed results
would actually have been unexpected by an ordinary artisan, attorney
argument regarding unexpected results is insufficient to show
nonobviousness. See In re Geisler, 116 F.3d 1465, 1471 (Fed. Cir. 1997).
It is also well settled that "any superior property must be unexpected
to be considered as evidence of non-obviousness." Pfizer, Inc. v. Apotex,
Inc., 480 F.3d 1348, 1371 (Fed. Cir. 2007) (emphasis in original).
In the present case, in describing the results of the experiments
conducted in Example 11, the Specification states that "[a] significant
difference was observed between the 20kD PEG conjugated docetaxel group
versus free docetaxel at 10 mg/kg." Spec. ,r 255. Appellants, however, do
not explain specifically why it would have been unexpected that a conjugate
having a moiety specifically targeting the linked drug to the tumor tissue
would be more effective than a drug to which no targeting moiety was
attached.
In sum, for the reasons discussed, Appellants do not persuade us that
the evidence of record fails to support the Examiner's prima facie case of
obviousness as to representative claim 2. For the reasons discussed,
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Appellants also do not persuade us that the objective evidence advanced to
show nonobviousness through unexpected results is sufficient to outweigh
the evidence of prima facie obviousness presented by the Examiner.
Because the preponderance of the evidence, therefore, supports the
Examiner's conclusion that the compound of claim 2 would have been
obvious to an ordinary artisan in view of Breitenkamp, Ahlgren, Veronese,
and Crown, we affirm the Examiner's rejection of claim 2 over those
references. Claims 5, 23, and 29-33 fall with claim 2. See 37 C.F.R.
§ 4I.37(c)(l)(iv).
SUMMARY
We affirm the Examiner's rejection of claims 2, 5, 23, and 29-33,
under 35 U.S.C. § 103(a) for obviousness over Breitenkamp, Ahlgren,
Veronese, and Crown.
TIME PERIOD
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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