Minnie Mcmillan et al.

Patent Trials and Appeals Board

Jul 23, 2019

14390930 - (D) (P.T.A.B. Jul. 23, 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.
14/390,930 10/06/2014 Minnie McMillan USC0115PUSA 1304
22045 7590 07/23/2019
Brooks Kushman
1000 Town Center
22nd Floor
Southfield, MI 48075
EXAMINER
HAMMELL, NEIL P
ART UNIT PAPER NUMBER
1636
NOTIFICATION DATE DELIVERY MODE
07/23/2019 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):
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PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
__________

Ex parte MINNIE MCMILLAN and LYNN E. FOSTER1
__________

Appeal 2019-002727
Application 14/390,930
Technology Center 1600
__________

Before RYAN H. FLAX, RACHEL H. TOWNSEND, and
CYNTHIA M. HARDMAN, Administrative Patent Judges.

HARDMAN, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134 involving claims directed to a
method for protecting a subject against radiation-induced DNA damage. We
have jurisdiction under 35 U.S.C. § 6(b).
We affirm.
STATEMENT OF THE CASE
The Specification states that needs exist for “drugs that protect against
exposure to radiation in the context of terrorism, nuclear accident or
radiological or nuclear attacks during warfare,” and for “improved methods

1 Appellants identify the real party in interest as “University of Southern
California.” Appeal Br. 1.
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that protect individuals from radiation exposure.” Spec. ¶¶ 4, 8. The
disclosed method “includes a step of introducing mammalian cells into the
subject, the mammalian cells having been treated ex vivo to insert therein a
polynucleotide encoding polypeptide that is protective against radiation,”
wherein the “mammalian cells express in vivo in the subject a therapeutically
effective amount of the polypeptide thereby reducing a symptom of radiation
exposure.” Id. ¶ 9.
Claims 1–11 and 26 are on appeal. Final Act. 2. Claim 1, the only
independent claim, reads as follows:
1. A method for protecting a subject against radiation
induced DNA damage, the method comprising:
introducing mammalian cells into the subject, the
mammalian cells transduced with an expression vector including
a polynucleotide encoding a polypeptide and an expression
control sequence operably linked to the polynucleotide, the
mammalian cells expressing the polypeptide,
at least 10% of the polypeptide includes amino acid
residues selected from the group consisting of cysteine,
tryptophan, phenylalanine, tyrosine and combinations thereof.
Appeal Br. Appendix 1.
The following rejections are before us on appeal:
Claims 1–11 are rejected under 35 U.S.C. § 112 for lack of
enablement. Final Act. 3.
Claims 1, 2, 4–7, 9, and 11 are rejected under 35 U.S.C. § 103 as
obvious over Weiner2 in view of Rodemann.3 Id. at 12.

2 Weiner et al., US 6,274,136 B1, issued Aug. 14, 2001.
3 Rodemann, US 6,645,934 B1, issued Nov. 11, 2003.
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Claim 26 is rejected under 35 U.S.C. § 103 as obvious over Weiner,
Rodemann, and Hammond.4 Id.
Claims 1, 2, 4–7, 9, 11, and 26 are rejected under 35 U.S.C. § 103 as
obvious over Weiner, Rodemann, and Dittmann.5 Id. at 15–16.
Claim 3 is rejected under 35 U.S.C. § 103 as obvious over Weiner,
Rodemann, Dittmann, and Tasaki.6 Id. at 16.
Claim 8 is rejected under 35 U.S.C. § 103 as obvious over Weiner,
Rodemann, Dittmann, and Rodino-Klapac.7 Id. at 17.
Claim 10 is rejected under 35 U.S.C. § 103 as obvious over Weiner,
Rodemann, Dittmann, and Zhao.8 Id. at 18.

DISCUSSION
“[T]he examiner bears the initial burden . . . of presenting a prima
facie case of unpatentability. If that burden is met, the burden of coming
forward with evidence or argument shifts to the applicant.” In re Oetiker,

4 Rosemarie W. Hammond et al., Molecular Cloning and Analysis of a Gene
Coding for the Bowman-Birk Protease Inhibitor in Soybean, 259 (15) J.
BIOL. CHEM. 9883–90 (1984).
5 Klaus H. Dittmann et al., Characterization of the amino acids essential for
the photo- and radioprotective effects of a Bowman-Birk protease inhibitor-
derived nonapeptide, 14(3) PROTEIN ENG. 157–60 (2001).
6 Takafumi Tasaki & Yong Tae Kwon, The mammalian N-end rule pathway:
new insights into its components and physiological roles, 32(11) TRENDS
BIOCHEM. SCI. 520–28 (2007).
7 Louise R. Rodino-Klapac et al., Persistent Expression of FLAG-tagged
Micro-dystrophin in Nonhuman Primates Following Intramuscular and
Vascular Delivery, 18(1) MOL. THER. 109–17 (2010).
8 Yi Zhao et al., Soluble factor(s) from bone marrow cells can rescue
lethally irradiated mice by protecting endogenous hematopoietic stem cells,
33 EXP. HEMATOL. 428–34 (2005).
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977 F.2d 1443, 1445 (Fed. Cir. 1992). We have considered those arguments
made by Appellants in the Appeal Brief; arguments not so presented in
Appellants’ brief are waived. See 37 C.F.R. § 41.37(c)(1)(iv) (2015); see
also Ex Parte Borden, 93 USPQ2d 1473, 1474 (BPAI 2010) (informative)
(“Any bases for asserting error, whether factual or legal, that are not raised
in the principal brief are waived.”).
Enablement
The Examiner stated that “the specification, while being enabling for
protecting a subject against radiation induced DNA damage by introducing
mammalian cells into a subject, the mammalian cells transduced with an
expression vector including a polynucleotide encoding a polypeptide,
wherein the polypeptide comprises SEQ ID NO 2,” is not otherwise enabled
to the full scope of the claims. Final Act. 3. The Examiner provided an
analysis of relevant factors set forth in In re Wands, 858 F.2d 731 (Fed. Cir.
1988), noting, for example, that the structure of the claimed polypeptide
“broadly encompasses a massive genus of possible polypeptides” (Final Act.
4), and that “[t]he state of the art regarding agents for protecting a subject
against radiation induced DNA damage is poorly described and
unpredictable.” Id. at 5.
The Examiner stated:
The specification broadly suggests that a polypeptide
would be protective against radiation if it includes at least 2
amino acid residues selected from the group consisting of
cysteine, tryptophan, phenylalanine, tyrosine, and combinations
thereof ([0030]). However, there is no specific evidence from
the specification that would support that a polypeptide would be
protective against radiation provided it contains these amino
acids. Therefore, this appears to be an assertion from the
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specification and claimed that is not supported by specific
evidence. . . . There is no specific evidence that would support
the conclusion that any polypeptide containing such amino acids
would protect against radiation induced DNA damage
independent of its function as determined by its amino acid
sequence structure. This assertion is also highly unpredictable at
least in view of Dynan [US 2008/0273660] who describes such
polypeptides that read on the polypeptides recited by the claims
actually inhibit DNA repair, as discussed above.
Final Act. 6.
We adopt the Examiner’s findings of fact and reasoning with respect
to non-enablement, and determine that the Examiner has made a prima facie
case of non-enablement as to claims 1–11. Final Act. 3–11; Ans. 15–18.
We address Appellants’ arguments below.
Relying on the Declaration of inventor Prof. Minnie McMillan,
Appellants argue that it is the claimed amino acids that impart the
radioprotective effect, such that the “mere incorporation of such amino acids
in a polypeptide regardless of the order will result in a radioprotective
polypeptide.” Appeal Br. 2; see also id. at 1–3; Reply Br. 1. We are not
persuaded by this argument. We agree with the Examiner that evidence of
record calls into question whether the full scope of the claims is enabled.
See, e.g., Final Act. 5–6 (discussing Dynan, US 2008/0273660 A1, issued
Nov. 6, 2008); 10–11 (discussing Roberts (Amino acids and their derivatives
as radioprotective agents, 3 AMINO ACIDS 25–52 (1992)); Ans. 16. And, as
the Examiner explained, Prof. McMillan’s declaration is not sufficient to
overcome the rejection supported by such evidence, for at least the reason
that the conclusory position that “the mere presence of radioprotective
amino acids in a polypeptide results in radioprotective properties for the
polypeptide regardless of the details regarding the positioning of such amino
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acids” is not supported by the cited Roberts publication, which does not
suggest that any polypeptide in which 10% of the polypeptide comprising
the amino acids recited by the claims would be sufficient for ‘protecting a
subject against radiation induced DNA damage’; indeed, Prof. McMillan’s
opinion is specifically rebutted by Dynan, which “teaches a polypeptide as
broadly claimed that increases the intrinsic sensitivity of cells to radiation-
induced DNA double-strand breaks by inhibiting DNA repair.” See, e.g.,
Final Act. 6, 7–11; Ans. 16–17. Moreover, as the Examiner explained, Prof.
McMillan’s opinion is “not based on any specific scientific rationale.” Ans.
16–17.
Thus, for the reasons provided by the Examiner, we affirm the
rejection of claims 1–11 under 35 U.S.C. § 112 for lack of enablement.
Obviousness
The Examiner found that Weiner teaches a method for delivering a
therapeutic polypeptide to a subject via introduction of mammalian cells
modified to express a polypeptide of interest, but does not teach that the
polypeptide is the Bowman-Birk protease inhibitor (“BBI”). Final Act. 12.
The Examiner further found that Rodemann teaches that the BBI and
fragments thereof have a radioprotective effect, and that Hammond teaches
the amino acid sequence of the BBI. Id. at 12–13, 14, 15. The Examiner
found that
It would have been obvious to one of ordinary skill in the
art at the time the invention was made to have applied the method
of Weiner to provide a radioprotective effect by transducing a
cell with an expression vector that encodes the BBI polypeptide
because it would have merely amounted to a simple combination
of prior art elements according to known method[s] to yield
predictable results. One would have been motivated to do so for
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the advantage of treating radiation exposure. One would have
had a reasonable expectation of success in doing so because
Rodemann teaches that administering BBI to a body area
affected by irradiation is useful for reducing a symptom of
radiation exposure, as discussed above. Since Weiner’s method
is useful for delivery [of] therapeutic polypeptides by expressing
and secreting the polypeptides from a cell, one would have had a
reasonable expectation of success in delivering BBI to the
affected body area by Weiner’s method.
Id. at 13.
With respect to the obviousness rejection that adds Dittmann, the
Examiner found that Dittmann teaches that BBI exerts photo and
radioprotective activity when cells are exposed to ionizing radiation, and that
the mechanism of these activities likely involves the activation of DNA
repair. Id. at 16.
With respect to claim 10, the Examiner added Zhao to the rejection,
finding that Zhao teaches a method for rescuing irradiated mice by providing
therapeutic polypeptides to the mice via a TheraCyte™ immunoisolation
device. Id. at 19. The Examiner found that “[i]t would have been obvious to
one of ordinary skill in the art at the time the invention was made to have
delivered the mammalian cells using a TheraCyte device because it would
have merely amounted to a simple combination of prior art elements
according to known methods to yield predictable results.” Id.
We adopt the Examiner’s findings of fact regarding the scope and
content of the prior art (Final Act. 12–20; Ans. 18–21), and determine that
the Examiner has made a prima facie case of obviousness. We address
Appellants’ arguments below.
Appellants appear to suggest that utilization of a known therapeutic
compound via known technologies can be nonobvious. Appeal Br. 4. While
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we agree with such a proposition in general, we also agree with the
Examiner’s analysis of the facts of this case, wherein Appellants’ claims
comprise a simple combination of prior art elements according to known
methods to yield predictable results.
Appellants point to a number of distinctions between Weiner and the
current claims, including the type of therapeutic relief at issue, the
polynucleotides secreted from the administered cells, whether the treatment
is preventative or responsive, and the method of administering the
polynucleotide to the subject. Id. at 4–5. Appellants also point to a number
of distinctions between Dittmann, Rodemann, and the current claims, such
as noting that neither Dittmann nor Rodemann teach how to use mammalian
cells to protect a subject or disclose administration or dosage when
introducing mammalian cells secreting the radioprotective compounds. Id.
at 6. We are not persuaded by these arguments, because the pending
obviousness rejections are based on the combined teachings from a number
of references, the facts of which are not rebutted by Appellants. Appellants
cannot show nonobviousness by attacking references individually as failing
to teach all of the claimed limitations when the rejection is based on a
combination of references, whose teachings together render obvious the
claimed invention. In re Keller, 642 F.2d 413, 426 (CCPA 1981); see also
Ans. 18–19 (noting that the passages Appellants quoted from Weiner do not
refute the teachings of Weiner, the teachings of Rodemann, or the rationale
to combine the two references as discussed in the rejection, and rejecting
Appellants’ piecemeal analysis of the rejection); Ans. 20–21.
Appellants also argue that Rodemann and Dittmann demonstrate
“difficulty and uncertainty” in the art, e.g., uncertainty associated with
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“taking a known chemical characteristic and making it more therapeutically
or pharmaceutically viable.” Appeal Br. 4, 5–6. We are not persuaded by
this argument, because it relies on biological uncertainty in general, without
providing any specific argument regarding why such uncertainty would have
led to a lack of motivation or lack of reasonable expectation of success in
this case.
Appellants additionally assert that claims 2 and 9 are “independently
allowable and nonobvious” because of the difference in amino acid fragment
size, stating: “[t]he present invention discloses BBI fragments of 10–40
amino acids, whereas Rodemann discloses a much smaller fragment such as
7–9 amino acids for distribution in tissue.” Appeal Br. 5. We are not
persuaded by this argument. As indicated by the Examiner, claim 2 recites a
polypeptide comprising “from about 10 to about 40 amino acid residues.”
We agree with the Examiner that Rodemann’s teaching of a polypeptide
having nine amino acid residues meets claim 2’s recitation of “about 10”
amino acids. Final Act. 13–14. Claim 9 recites that the polypeptide can be
the BBI or a fragment comprising “10 to 40 amino acid resides.” Id. at 15;
Ans. 20. As indicated by the Examiner, Rodemann discloses the BBI. Final
Act. 15.
With respect to claim 10, Appellants argue that “Zhao discloses
introduction of a domestic cell post exposure, whereas the current disclosure
involves introducing a cell designed to express a specific polypeptide with
radioprotective functionality prior to exposure,” and it “would not be
obvious that a mechanism of reactive treatment would be effective for
preventive treatment.” Appeal Br. 7. Like the Examiner, we are not
persuaded by this argument, “at least because the claims do not require
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exposing a subject to damaging radiation.” Final Act. 19; Ans. 21. Further,
recitation of “protecting a subject against radiation induced DNA damage”
appears only in the preamble of claim 1. As our reviewing court has stated,
“as a general rule preamble language is not treated as limiting,” including
where “a patentee defines a structurally complete invention in the claim
body and uses the preamble only to state a purpose or intended use for the
invention.” Arctic Cat Inc. v. GEP Power Prods., Inc., 919 F.3d 1320, 1327,
1328 (Fed. Cir. 2019) (citations omitted). Here, the body of claim 1 recites a
single step, i.e., introducing mammalian cells that have been transduced so
as to express a polypeptide that has at least 10% of its amino acids being
from a particular named group of amino acids into a subject, and does not
relate that step back to the preamble’s purpose or intended use for the
method. We conclude, therefore, that the body of the claim defines a
complete invention. Accordingly, Appellants’ attempt to distinguish Zhao
on the basis of reactive versus preventive treatment additionally fails
because nothing limits the appealed claims to preventative methods.

SUMMARY
We affirm the rejection of claims 1–11 under 35 U.S.C. § 112 for lack
of enablement.
We affirm the rejection of claims 1, 2, 4–7, 9, and 11 under 35 U.S.C.
§ 103 as obvious over Weiner and Rodemann.
We affirm the rejection of claim 26 under 35 U.S.C. § 103 as obvious
over Weiner, Rodemann, and Hammond.
We affirm the rejection of claims 1, 2, 4–7, 9, 11, and 26 under
35 U.S.C. § 103 as obvious over Weiner, Rodemann, and Dittmann.
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We affirm the rejection of claim 3 under 35 U.S.C. § 103 as obvious
over Weiner, Rodemann, Dittmann, and Tasaki.
We affirm the rejection of claim 8 under 35 U.S.C. § 103 as obvious
over Weiner, Rodemann, Dittmann, and Rodino-Klapac.
We affirm the rejection of claim 10 under 35 U.S.C. § 103 as obvious
over Weiner, Rodemann, Dittmann, and Zhao.
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)(1)(iv).

AFFIRMED