Altor BioScience Corporation

Patent Trials and Appeals Board

Jul 28, 2021

2021001237 (P.T.A.B. Jul. 28, 2021)

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.
14/388,575 09/26/2014 Jinghai Wen 8774ALT-10-PUS 8657
157773 7590 07/28/2021
Sheridan Ross PC
1560 Broadway
Suite 1200
Denver, CO 80202
EXAMINER
JIANG, DONG
ART UNIT PAPER NUMBER
1646
NOTIFICATION DATE DELIVERY MODE
07/28/2021 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):
e-docket@sheridanross.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
________________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
________________

Ex parte JINGHAI WEN, WENXIN XU,
PETER RHODE, and HING C. WONG1
________________

Appeal 2021-001237
Application 14/388,575
Technology Center 1600
________________

Before JEFFREY N. FREDMAN, JOHN G. NEW, and DAVID COTTA,
Administrative Patent Judges.

NEW, Administrative Patent Judge.

DECISION ON APPEAL

1 We use the term “Appellant” to refer to the “applicant” as defined in
37 C.F.R. § 1.142. Appellant identifies Altor BioScience Corporation as
the real party-in-interest. App. Br. 3. Oral argument was heard on July 15,
2021, and a transcript of the hearing is part of the record.
Appeal 2021-001237
Application 14/388,575

2
SUMMARY
Appellant files this appeal under 35 U.S.C. § 134(a) from the
Examiner’s Final Rejection of claims 1, 4, 7–9, 12, 15, 16, 19, 22–24, 27,
30–31, 34, 37–39, 42, 45–46, 61, 64, 67–69, 72, 75–77, and 79 as
unpatentable under 35 U.S.C. § 103(a) as being obvious over the
combination of Wong et al. (WO 2009/117117 A1, September 24, 2009)
(“Wong”) and H. von der Maase et al., Long-Term Survival Results of a
Randomized Trial Comparing Gemcitabine Plus Cisplatin, With
Methotrexate, Vinblastine, Doxorubicin, Plus Cisplatin in Patients With
Bladder Cancer, 23(21) J. CLIN. ONCOL. 4602–08 (2005) (“von der Haase”).
We have jurisdiction under 35 U.S.C. § 6(b).
We AFFIRM.

NATURE OF THE CLAIMED INVENTION
Appellant’s claimed invention is directed to methods of treating
neoplasia, for example bladder cancer, by administering an IL-2 fusion
protein and one or more therapeutic agents, where the IL-2 fusion protein
does not necessarily have to target the neoplasia. Spec. Abstr.

REPRESENTATIVE CLAIM
Independent claim 1 is representative of the claims on appeal and
recites:
1. A method of ameliorating cancer in a subject in need
thereof comprising:

administering a composition consisting of an effective amount of
an IL-2 fusion protein, cisplatin, and gemcitabine to the subject
Appeal 2021-001237
Application 14/388,575

3
in need thereof, wherein the IL-2 fusion protein comprises a T
cell receptor (TCR),

thereby ameliorating the cancer.

App. Br. 10.

ISSUE AND ANALYSIS
We agree with, and adopt, the Examiner’s findings, reasoning, and
conclusion that the claims are obvious over the combined cited prior art. We
address below the arguments raised by Appellant.

Issue
Appellant argues that the Examiner erred in concluding that the claims
are obvious over the combined cited prior art, notwithstanding Appellant’s
evidence of allegedly unexpected results. App. Br. 7.

Analysis
The Examiner finds that Wong teaches that traditional approaches to
the treatment of diseases such as cancers and autoimmune and infective
diseases, including surgery, radiation chemotherapy, antibiotics or
combination therapies have generally not proven effective. Non-Final Act. 3
(citing Wong 1). The Examiner finds that Wong teaches that development
of alternate remedies for preventing and/or treating human diseases is
crucial, and immunotherapy and gene therapy approaches utilizing
antibodies and T-lymphocytes have emerged as new and promising methods
for treating human disease. Id.
Appeal 2021-001237
Application 14/388,575

4
Specifically, the Examiner finds that Wong teaches a Phase 1 Clinical
Trial of ALT-801 (i.e., the claimed IL-2 fusion protein comprising a T cell
receptor), in which ALT-801 is evaluated in a multi-course dose-escalation
Phase I/IIa clinical study in patients with metastatic malignancies that
express HLA-A2/p53 peptide complexes, the antigenic target of ALT-801.
Non-Final Act. 22 (citing Wong 73–79). The Examiner finds that Wong also
teaches that ALT-801 treatment at the MTD level provided favorable
pharmacokinetics and immunostimulatory activity necessary for antitumor
responses. Id. at 3–4 (citing, e.g., Wong, 77). The Examiner finds that
Wong teaches that ALT-801 (c264scTCR-IL2) is a recombinant humanized
soluble single-chain T-cell receptor (“TCR”)-cytokine fusion protein, the
amino acid sequences of which are shown in Wong’s Fig. 36. Id. at 7.
The Examiner finds that Wong also teaches that TCR fusion and
conjugate complexes comprise a biologically active or effector molecule
covalently linked to the TCR molecule, which includes, chemotherapeutic
agents such as, among others, cisplatin, suggesting combination therapies.
Non-Final Act. 4 (citing Wong, 16, 18). However, the Examine finds that
Wong does not expressly teach, or suggest, a specific combination therapy
comprising ALT-801, cisplatin and gemcitabine. Id.
The Examiner finds that von der Maase teaches a study that compares
long-term survival in patients with locally advanced or metastatic
transitional cell carcinoma (“TCC”) treated with gemcitabine/cisplatin

2 In the Final Office Action, the Examiner incorporated by reference the
findings and conclusions of the Non-Final Office Action of April 4, 2019.
See Final Act. 2. We consequently refer to the latter action in discussing
the Examiner’s findings and conclusions.
Appeal 2021-001237
Application 14/388,575

5
(“GC”) or methotrexate/vinblastine/doxorubicin/cisplatin (“MVAC”). Non-
Final Act. 4. The Examiner finds that von der Maase teaches that long-term
overall and progression-free survival after treatment with GC or MVAC are
similar, which indicates the employment of GC as a standard of care in
patients with locally advanced or metastatic TCC. Id. The Examiner finds
that von der Maase teaches that this is so because MVAC treatment is
associated with substantial toxicities and death. Id. (citing von der Maase,
Abstr., 4602).
The Examiner concludes that it would therefore have been prima facie
obvious to a person of ordinary skill in the art to combine in ALT-801 and
GC (gemcitabine plus cisplatin), or ALT-801 and gemcitabine (or
cisplatin) in a combination therapy (i.e., immunotherapy and chemotherapy)
for treating cancer or metastatic malignancies. Non-Final Act. 4. The
Examiner reasons that a skilled artisan would have been motivated to do so
to obtain the therapeutic advantages of combination therapy, which
potentially increases the efficacy and reduces toxicity. Id. The Examiner
also reasons that a person of ordinary skill in the art would have reasonably
expected success in combining the teachings of the references because ALT-
801, gemcitabine, cisplatin and GC have each been demonstrated to be
effective in the treatment of cancer. Id. at 5.
Appellant’s Appeal Brief does not contest the Examiner’s conclusion
that the claims are prima facie obvious over the teachings of the combined
cited prior art, thereby effectively waiving any contest upon that point. See
37 C.F.R. § 41.37 (c)(iv) (“[A]ny arguments or authorities not included in
the appeal brief will be refused consideration by the Board for purposes of
the present appeal”). Rather, Appellant relies upon the allegedly unexpected
Appeal 2021-001237
Application 14/388,575

6
and surprising results disclosed in the Specification as overcoming the
Examiner’s conclusion that the claims are obvious. App. Br. 7–8.
Specifically, Appellant argues that the Specification discloses that that
adding ALT-801 to GC therapy enhances anti-tumor potency relative to GC
alone, while reducing patient toxicity compared to GC alone. Id. at 8 (citing
Spec. Figs. 1, 4).
Appellant contends that it is well established in the art that
combination therapies tend to have both greater anti-cancer potency and
more toxicity. App. Br. 8. In support of this contention, Appellant cites
Carrick et al. (2009) Cochrane Database Syst. Rev. 2:CD003372,
doi:10.1002/14651858.CD003372.pub3 (2009) (“Carrick”).3 According to
Appellant, Carrick teaches that: “Combination chemotherapy regimens show
a statistically significant advantage for survival … in women with metastatic
breast cancer but they also produce more toxicity.” Id. (quoting Carrick
Abstr.). Appellant interprets this to mean that, although a person of ordinary
skill in the art might well expect the 3-drug combination of ALT-801/GC to
be more potent than the 2-drug GC combination, that skilled artisan would
also, prior to Appellant’s disclosure, have expected that the 3-way
combination would be more toxic to the patient. Id.
Appellant asserts that it has unexpectedly discovered that the 3-way
combination has more anti-tumor potency than the 2-way GC combination,
but demonstrates surprisingly less toxicity. App. Br. 8. According to
Appellant, nothing in the teachings of Wong or von der Maase, considered
either individually or in combination, suggests that the addition of ALT-801

3 The Carrick reference has not been entered into the record of this appeal.
Appeal 2021-001237
Application 14/388,575

7
to GC combination therapy might enhance anti-tumor potency while
simultaneously reducing patient toxicity relative to GC combination therapy
without ALT-801. Id. Appellant asserts that this allegedly surprising and
advantageous discovery is objective proof of the non-obviousness of
Appellant’s claimed invention. Id.
We are not persuaded by Appellant’s arguments that the results
depicted in Figures 1 and 4 of Appellant’s Specification are probative of
unexpected or surprising results. Figure 1 of Appellant’s Specification is
reproduced below.

Figure 1 of Appellant’s depicts changes in mean tumor volume
of subcutaneous human UMUC-14 bladder tumor xenografts in
nude mice over 40 days with two treatment cycles of
gemcitabine/cisplatin; ALT-801; or gemcitabine/cisplatin/
ALT-801
We agree with Appellant that Figure 1 of the Specification exhibits
increased efficacy of ALT-801/CG over GC and, possibly, over ALT-801,
although the latter is uncertain. However, we are not persuaded that the
Appeal 2021-001237
Application 14/388,575

8
combination therapy of ALT-801/GC “reduc[es] patient toxicity relative to
GC combination therapy without ALT-801,” as Appellant contends. See
App. Br. 8.
Appellant’s Figure 4 is reproduced below:

Figure 4 of Appellant’s Specification depicts the effects of
ALT-801 and MART-lscTCR/IL-2, in combination with
chemotherapy regimens, on mouse body weight

With respect to Figure 4, the Specification discloses that:
There was no observed mortality during the treatment regimen.
However, at several time points during the treatment course,
significant body weight loss was observed in the Gem+Cis and
ALT-801+Gem[citabine]+Cis[platin] treatment groups
compared to animals not treated with Cis (Figure 4). No
significant difference in anti-tumor activity was found by using
Cis and the recovery from the weight loss was slow indicating a
higher toxicity of Cis in this model. These results show that Cis
does not provide therapeutic benefit in this treatment. Body
weight loss was also found in both ALT-801+Gem and MART-
lscTCR/IL-2+Gem treatment groups when compared to PBS
group, however, mean mouse body weights for both the ALT-
801+Gem and MART-lscTCR/IL-2+Gem treatment groups
Appeal 2021-001237
Application 14/388,575

9
recovered rapidly during the 11-day rest period and 13-day
follow-up period. These findings demonstrate that the ALT-
801+Gem and MART-lscTCR/IL-2+Gem treatment regimens
are well tolerated with transient toxicities in this model.

Spec. 46.
Several things stand out to us from Figure 4. Most importantly, there
are no data in Figure 4 concerning toxicity-induced weight loss following
administration of ALT-801 alone. This is a confounding factor for
Appellant’s analysis, because without such data we cannot determine
whether administration of ALT-801 by itself produces significant toxicity-
induced weight loss, or how much toxicity ALT-801 might actually
contribute to combined ALT/-801/GC administration. Furthermore, co-
administration of ALT-801/G (without cisplatin) does not appear to induce
significantly greater toxicity than administration of the control phosphate
buffer solution (“PBS”), indicating that co-administration of ALT-801 and G
together produce very little in the way of toxic side effects.
This is consistent with the teachings of Wong, which discloses that:
Given that [ALT-801] was as effective as a 12-fold higher
cumulative dose of [non-targeted IL-2] in reducing tumor burden
without the overt signs of toxicity, this study provides additional
support that [ALT-801] offers safer and more effective treatment
for cancer than current high dose [non-targeted IL-2] therapies.

Wong, 65 (emphasis added).
Furthermore, it is evident from Appellant’s Figure 4 that the
pronounced toxicity of co-administered GC is not significantly different
from that of co-administered ALT-801/GC. Given that co-administration of
ALT-801/G appears to produce little, if any, toxicity-induced weight loss,
the pronounced toxicity-induced weight loss appears to arise primarily from
Appeal 2021-001237
Application 14/388,575

10
the administration of cisplatin (data concerning the toxicity of cisplatin
administration alone is not available from Figure 4, or otherwise disclosed
by Appellant’s Specification).
Summarizing, it is evident from Figure 4 that the primary driver of
toxicity-induced weight loss in this study is derived from the toxicity of
cisplatin. Administration of ALT-801/GC had near-identical results to
administration of GC, whereas administration of ALT-801/G did not appear
to induce significantly more weight loss than the control PBS.
Consequently, we conclude that Appellant’s results are neither surprising
nor unexpected: a person of ordinary skill in the art, comprehending Figure 4
of the Specification would likely conclude that ALT-801 and G contribute
very little to the toxicity of administered ALT-801/GC. More likely, the
skilled artisan would expect to see a toxicity-induced weight loss of ALT-
801/GC co-administration that is comparable to that of co-administration of
GC, and possibly of C administration alone.
We therefore do not find persuasive Appellant’s argument that it is
unexpected and surprising that administration of ALT-801/GC “reduc[es]
patient toxicity relative to GC combination therapy without ALT-801,” or
even fails to increase the toxicity of ALT-801/GC administration compared
to GC. Consequently, we do not find that the results depicted in Figure 4 are
sufficient when considered with the Examiner’s prima facie conclusion of
obviousness, and we affirm the Examiner’s rejection of the claims.

Appeal 2021-001237
Application 14/388,575

11
CONCLUSION
The rejection of claims 1, 4, 7–9, 12, 15, 16, 19, 22–24, 27, 30–31, 34,
37–39, 42, 45–46, 61, 64, 67–69, 72, 75–77, and 79 as unpatentable under
35 U.S.C. § 103(a) is affirmed.
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136.

AFFIRMED

Claim(s)
Rejected
35 U.S.C. § Reference(s)/Basis Affirmed Reversed
1, 4, 7–9, 12,
15, 16, 19, 22–
24, 27, 30–31,
34, 37–39, 42,
45–46, 61, 64,
67–69, 72, 75–
77, 79
103(a) Wong, van der Haase 1, 4, 7–9,
12, 15, 16,
19, 22–24,
27, 30–31,
34, 37–39,
42, 45–46,
61, 64, 67–
69, 72, 75–
77, 79