MELCHER, CHRISTOPH et al.

Patent Trials and Appeals Board

Nov 13, 2020

14937142 - (D) (P.T.A.B. Nov. 13, 2020)

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.
14/937,142 11/10/2015 CHRISTOPH MELCHER MR1035-2463 1089
4586 7590 11/13/2020
ROSENBERG, KLEIN & LEE
3458 ELLICOTT CENTER DRIVE-SUITE 101
ELLICOTT CITY, MD 21043
EXAMINER
FISCHER, JOSEPH
ART UNIT PAPER NUMBER
1658
NOTIFICATION DATE DELIVERY MODE
11/13/2020 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):
ptoactions@rklpatlaw.com
ptoactions@yahoo.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte CHRISTOPH MELCHER
Appeal 2020-000428
Application 14/937,142
Technology Center 1600
Before ERIC B. GRIMES, LINDA M. GAUDETTE, and
FRANCISCO C. PRATS, Administrative Patent Judges.
GAUDETTE, Administrative Patent Judge.
DECISION ON APPEAL1
The Appellant2 appeals under 35 U.S.C. § 134(a) from the Examiner’s
decision finally rejecting claims 1, 2, 4–9, and 11–15.3
We AFFIRM.

1 This Decision includes citations to the following documents: Specification
filed Nov. 10, 2015, as amended (“Spec.”); Final Office Action dated Dec.
28, 2018 (“Final Act.”); Appeal Brief filed May 21, 2019 (“Appeal Br.”);
and Examiner’s Answer dated Aug. 22, 2019 (“Ans.”).
2 We use the word “Appellant” to refer to “applicant” as defined in 37
C.F.R. § 1.42. The Appellant identifies the real party in interest as the
inventors. Appeal Br. 1.
3 We have jurisdiction under 35 U.S.C. § 6(b).
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CLAIMED SUBJECT MATTER
Metallothionein (MT) proteins “are low molecular weight, single
chain polypeptides with extraordinarily high content of the amino acid
cysteine.” Id. at 2:23–24. The sulfhydryl groups of cysteine residues enable
MT proteins to bind metal ions, scavenge reactive species, display
antioxidant activity, and respond to changes in intracellular redox potential.
Id. at 2:24–26 (citation omitted). “The present invention relates to
production of hypo-metallated redox-active [MT] proteins, particularly to
production of MT proteins with defined numbers of MT cysteinyl binding
sites occupied with physiologically relevant metal ions.” Id. at 1:9–11.
Hypo-metallated redox-active MT proteins produced by the inventive
method may be used to manufacture medicaments for treating conditions
originating from elevated intracellular oxidative stress, dis-balanced
intracellular redox-potential, or redox-potential-dependent imbalance of
metal ions. Id. at 9:19–23. Claim 1, reproduced below, is illustrative of the
claimed subject matter:
1. A method for producing a hypo-metallated redox-
active metallothionein protein, the hypo-metallated
redox-active metallothionein protein having 20 cysteine
sulfhydryl groups and 7 binding pockets, 2 to 16 of the
20 cysteine sulf[h]ydryl groups being free and reduced,
and l to 6 of the 7 binding pockets being occupied by
metal ions, comprising:
providing a metallothionein protein;
fully pre-metallating the metallathionein protein;
de-metallating the metallothionein protein;
chemically reducing all the 20 cysteine
sul[f]hydryl groups of the de-metallated metallothionein
protein; and
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partially metallating the reduced de-metallated
metallothionein protein by providing 1, 2, 3, 4, 5, or 6
metal ions to the 7 binding pockets.
Appeal Br. 35 (Claims App.).
REJECTIONS
1. Claims 1, 2, and 4–7 are rejected under 35 U.S.C. § 103 as
unpatentable over Ngu (Kinetic Analysis of Arsenic-Metalation of Human
Metallothionein: Significance of the Two-Domain Structure, JACS, 2008,
130, 17016–17028) in view of Merrifield (J. Inorg. Biochem. 88 (2002)
153–172).4
2. Claims 1, 2, and 4–9 are rejected under 35 U.S.C. § 103 as
unpatentable over Ngu in view of Merrifield and Kang (Exp. Biol. Med.
231:1459–1467, 2006).
3. Claims 1, 2, and 4–9 are rejected under 35 U.S.C. § 103 as
unpatentable over Ngu in view of Merrifield, Kang, and Maret
(Experimental Gerontology 43 (2008) 363–369).
4. Claims 1, 2, 4–7, and 11–13 are rejected under 35 U.S.C. § 103
as unpatentable over Ngu in view of Merrifield and IS (Inoue and Satoh,
Current Pharmaceutical Biotechnology, 2013, Vol. 14, No. 4, 391–393).
5. Claims 1, 2, 4–7, and 11–13 are rejected under 35 U.S.C. § 103
as unpatentable over Ngu in view of Merrifield and Datta (Cancer Res. 2007
March 15; 67(6): 2736–2746).

4 Although the Examiner includes claims 1, 2, and 4–7 in each ground of
rejection, the Examiner relies solely on the combination of Ngu and
Merrifield in rejecting these claims.
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6. Claims 1, 2, 4–7, 11, 12, and 14 are rejected under 35 U.S.C.
§ 103 as unpatentable over Ngu in view of Merrifield and Hozumi (Current
Pharmaceutical Biotechnology, 2013, 14(4), 408–413).
7. Claims 1, 2, 4–7, 11, 12, and 15 are rejected under 35 U.S.C.
§ 103 as unpatentable over Ngu in view of Merrifield and Cai
(METALLOTHIONEIN AS AN ADAPTIVE PROTEIN PREVENTS
DIABETES AND ITS TOXICITY, Nonlinearity in Biology, Toxicology,
and Medicine, 2:89–103, 2004).
OPINION
The Examiner found that Ngu discloses the claim 1 method except for
an explicit teaching of fully pre-metallating the MT protein. See Final Act.
4–6. As to the fully pre-metallating step, the Examiner found that Ngu cites
an intermediate reference for a teaching of the recombinant MT production
method used in Ngu’s experimental methods. Id. at 4. The Examiner found
that the intermediate reference, in turn, cites Merrifield. Id.; see also Ngu
17017 (citing Merrifield). The Examiner found that “Merrifield teaches that
the method applied by Ngu, and others in the field, fully metallates at least a
portion of the metallothionein protein produced and provided by the cells
during preparation from recombinant culture.” Final Act. 5 (finding that
Merrifield’s addition of a metal, such as cadmium, at a sufficient
concentration to stabilize indicates full metallation).
The Appellant suggests that Ngu and Merrifield are nonanalogous art
because they describe studies of the MT protein’s binding ability to toxic
metals or metalloids such as Cd or As, whereas the present invention’s
purpose is to form pharmaceutical compositions that are harmless to
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patients. Appeal Br. 16. We agree with the Examiner that this argument is
not persuasive. See Ans. 6–7. The Appellant has not identified, nor do we
find, any language in the claims or the written description that supports a
narrow interpretation of claim 1 as limited to a method of producing a
pharmaceutical composition. See, e.g., Spec. 8:12–13 (“The first aspect of
the present invention relates to a method for producing a hypo-metallated
redox-active metallothionein protein.”), 9:13–15 (“The second aspect of the
present invention relates to a pharmaceutical composition, which comprises
at least one hypo-metallated redox-active metallothionein protein produced
by the method described above.”).
The Appellant argues that the applied prior art does not disclose or
suggest de-metallating a fully pre-metallated metallathionein protein. See
Appeal Br. 14–15. More specifically, the Appellant argues that Merrifield
describes adding CdSO4 before the cells are lysed and, therefore, the CdSO4
is not “able to influence the MT protein in cells, let alone ‘fully pre-
metallat[e] the metallothionein protein.’” Id. at 15 (citing Merrifield § 2.2).
“In contrast, in the present method, the step of fully pre-metallating the MT
protein, [is] performed after the native protein [is] separated from host
cells.” Id. The Appellant further argues that “in Merrifield, the step of
metallating the MT protein, is not an initial pre-metallation, and is not
described as being followed by the steps of de-metallating, chemical
reduction, or final partial metallating, as provided in the claimed method.”
Id. at 17.
The Appellant’s arguments are not persuasive for the reasons
explained in the Answer. See Ans. 5–7. We add the following:
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There is a presumption that method steps need not be performed in the
recited order unless the claim specifically provides for such. Interactive Gift
Express, Inc. v. Compuserve Inc., 231 F.3d 859, 875–76 (Fed. Cir. 2000).
Neither the plain language of the claims nor the written description supports
narrowly interpreting the claim 1 method as precluding simultaneous
performance of the providing and fully pre-metallating steps. See, e.g., Spec.
16:8–25. Further, the Appellant does not provide persuasive evidentiary
support when arguing the drawbacks of adding CdSO4 before cell lysing (see
Appeal Br. 15) and has not shown error in the Examiner’s reasoned
explanation of why Cd fully occupies all metal binding sites (see Ans. 6). As
to the Appellant’s assertion that Merrifield does not describe the claim 1 de-
metallating, reducing, and partially metallating steps, this argument is not
persuasive of reversible error because the Examiner relies on Ngu for a
teaching of these steps. See Ans. 7.
The Appellant does not separately argue the patentability of claims 2
and 4–7. See Appeal Br. 18. Accordingly, we sustain the rejections of claims
1, 2, and 4–7 for the reasons stated in the Final Office Action, the Answer,
and above.
The Examiner cited Kang alone, or in combination with Maret, for
teachings of the dependent claim 85 and claim 9 limitations. Final Act. 9–11.
As explained by the Examiner (Ans. 8–10), the Appellant’s arguments (see
Appeal Br. 18–23) are not persuasive of reversible error because they focus
on the teachings of Kang or Maret, individually, and fail to consider what

5 Claim 8, as drafted, depends from claim 8. See Appeal Br. 37 (Claims
App.). For purposes of this decision, we have interpreted claim 8 as
depending from claim 7.
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the ordinary artisan would have understood from the references’ combined
teachings. As to the Appellant’s argument that Kang discloses only one of
the alternative reducing agents recited in claim 8, we add that the disclosure
of one alternative is sufficient for anticipation or obviousness. See Brown v.
3M, 265 F.3d 1349, 1351 (Fed. Cir. 2001) (“When a claim covers several
structures or compositions, either generically or as alternatives, the claim is
deemed anticipated if any of the structures or compositions within the scope
of the claim is known in the prior art.”). Therefore, we sustain the rejections
of claims 8 and 9 for the reasons stated in the Final Office Action, the
Answer, and above.
The Examiner found that each of IS and Datta teaches the limitations
of dependent claims 11–13. See Final Act. 11–15. The Examiner found that
Hozumi teaches the limitations of dependent claims 11, 12, and 14, and Cai
teaches the limitations of dependent claims 11, 12, and 15. See id. at 15–18.
The Appellant essentially argues that neither IS, Datta, Hozumi, nor
Cai cures the deficiencies in the Examiner’s rejection of claim 1 over Ngu
and Merrifield. Appeal Br. 23–29. These arguments are not persuasive
because the Appellant has not identified error in the rejection of claim 1, the
Examiner’s findings as to the secondary references’ teachings, or the
Examiner’s reasoning as to why the ordinary artisan would have further
modified the method resulting from the Ngu and Merrifield combination in
view of the secondary references’ teachings. See Ans. 12–16. Therefore, we
sustain the rejections of claims 11–15 for the reasons stated in the Final
Office Action, the Answer, and above.
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DECISION SUMMARY
Claims
Rejected
35 U.S.C. § Reference(s)/Basis Affirmed Reversed
1, 2, 4–7 103 Ngu, Merrifield 1, 2, 4–7
1, 2, 4–9 103 Ngu, Merrifield, Kang 1, 2, 4–9
1, 2, 4–9 103 Ngu, Merrifield, Kang,
Maret
1, 2, 4–9
1, 2, 4–7,
11–13
103 Ngu, Merrifield, IS 1, 2, 4–7,
11–13

1, 2, 4–7,
11–13
103 Ngu, Merrifield, Datta 1, 2, 4–7,
11–13

1, 2, 4–7,
11, 12, 14
103 Ngu, Merrifield,
Hozumi
1, 2, 4–7,
11, 12, 14

1, 2, 4–7,
11, 12, 15
103 Ngu, Merrifield, Cai 1, 2, 4–7,
11, 12, 15

Overall
Outcome:
1, 2, 4–9,
11–15

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