DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 97-98 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 97-98 recite the limitation “n”. There is insufficient antecedent basis for this limitation in the claim. For the purposes of applying art, “n” is interpreted as “nr”.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 94-95, 97, 99-101, 103, 106-107, are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Suli-Vargha et. al.1
Regarding instant claims 94-95, 97, 99-101, 103, 106-107, and a compound, Suli-Vargha teaches Compound 4, also known as CAS# 1001920-27-9 (see Suli-Vargha at p. 747 Scheme 1).
Suli-Vargha Compound 4
CAS# 1001920-27-9
Instant Claim 95 Formula
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148
278
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134
286
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CAS# 1001920-27-9 reads on the formula of claim 95 when X is null, Rr is
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102
146
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, n is 0, Gr is H, R1 is
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90
138
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, n1 is 1, G1 is H, R2 is
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88
148
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, n2 is 0, G2 is H, Rt is Rt*, Rt* is NH2.
Claim(s) 94-97, 99, 103, 106 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Nam et. al.2
Regarding instant claims 94, 95, 96, 97, 99, 103, 106, and a compound, Nam teaches Compound 4, also known as CAS# 714272-02-3 (see Nam at p. 3132 Figure 2).
Nam Compound 4
CAS# 714272-02-3
Instant Claim 96
Formula 2f
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122
242
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134
274
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CAS# 714272-02-3 reads on instant Formula 2f when X is CH2, Rr is
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48
66
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and nr is 0 and Gr is C6-10 aryl specifically phenyl substituted with OPO3H2 (see instant spec. at p. 14 lines 4-17, especially “Unless otherwise specified, each instance of an aryl group is independently unsubstituted…or substituted”), R1 is
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84
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and n1 is 2 and G1 is COOH, R2 is
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and n2 is 0 and G2 is C4 alkyl specifically sec-butyl, and Rt is Rt* and Rt* is OH.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim 98 is rejected under 35 U.S.C. 103 as being unpatentable over Suli-Vargha as applied to claims 94-95, 97, 99-101, 103, 106-107 above.
The prior art differs from the instant claims as follows: While Suli-Vargha teaches CAS# 1001920-27-9, CAS# 1001920-27-9 does not have an alkyl at the Gr position as in instant claim 98.
However,
Suli-Vargha teaches transformation to the diazepine ring occurs with not only glycine residues as in CAS# 1001920-27-9, but also with alanine and leucine residues, amino acids with alkyl groups at the R position (see Suli-Vargha at p. 747 Scheme 1 and p. 745 Table 1), corresponding with instant Rr wherein nr is 0 and Gr is C1-4 alkyl.
Suli-Varga Aspartimide Peptide Transformation Genus
Instant Claim 95 Formula
Instant Rr
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98
220
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140
282
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50
74
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Therefore, it would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to arrive at the instantly claimed invention with a reasonable expectation of success in view of the prior art for at least the following reason(s):
Regarding H for Me, per MPEP § 2144.08(II)(A)(4)(c), the closer the physical and/or chemical similarities between the claimed species or subgenus and any exemplary species or subgenus disclosed in the prior art, the greater the expectation that the claimed subject matter will function in an equivalent manner to the genus. In instant case, CAS# 1001920-27-9 differs only from claim 98 in a change of H for Me. Moreover, the prior art suggests a C1-4 alkyl at the R position by teaching the ring residue may be alanine (R = methyl) or leucine (R = isobutyl). It would have been obvious to substitute a methyl or isobutyl for H in the structure above as this is specifically contemplated by the reference to be a feasible alternative.
Furthermore, it is well-within the ordinary skill in art to incorporate a short-chain alkyl group in lieu of hydrogen.
Therefore, an artisan would arrive at the same invention as presently claimed for reasons taught in the prior art.
Claim 96 is rejected under 35 U.S.C. 103 as being unpatentable over Suli-Vargha as applied to claims 94-95, 97, 99-101, 103, 106-107 above and in further view of Neuberger et. al.3
The prior art differs from the instant claims as follows: While Suli-Vargha teaches CAS# 1001920-27-9, the stereochemistry of CAS# 1001920-27-9 is not shown.
However,
Regarding claim 96 and stereochemistry, Neuberger teaches asymmetric compounds have molecular rotations (see Neuberger at p. 310 “5. Effect of Substitution on Molecular Rotation”). Optically active amino acids contain only one hydrogen atom in the α-position (see Neuberger at p. 343). The majority of amino acids have chiral centers (see e.g., Neuberger at p. 304 Table III, p. 305 Table IV, p. 307 Table VI), notably not glycine (see Neuberger at p. 343). Racemization of amino acids to covert between stereoisomers is known (see Neuberger at pp. 339-343).
Therefore, it would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to arrive at the instantly claimed invention with a reasonable expectation of success in view of the prior art for at least the following reason(s):
An artisan would readily appreciate that since CAS# 1001920-27-9 comprises amino acids with chiral centers, it must fall under one of the stereochemistry orientations depicted in claim 96 since claim 96 lists all potential stereochemical orientations (for each of the four (4) chiral centers in the sequence, both (2) orientations are considered, 42 = 16 formulas). Moreover, an artisan could readily make any stereoisomer variant of CAS# 1001920-27-9, because converting between stereocenters in amino acids is known (as taught by Neuberger).
Furthermore, it is well-within the ordinary skill in art to:
appreciate the stereochemistry of amino acids in a known molecule comprising amino acids, and/or
make a stereoisomer variant of a known compound.
Therefore, an artisan would arrive at the same invention as presently claimed for reasons taught in the prior art.
Claims 108-113 are rejected under 35 U.S.C. 103 as being unpatentable over Suli-Vargha as applied to claims 94-95, 97, 99-101, 103, 106-107 above and in further view of FI 122054 B to Silfverberg et. al.4
The prior art differs from the instant claims as follows: While Suli-Vargha teaches the small molecule peptide CAS# 1001920-27-9, Suli-Vargha does not specify a consumable milk product.
However,
Regarding instant claims 108-113 and a consumable product or method of modulating flavor of a consumable product, Silfverberg teaches the addition of small molecule peptides in a dairy product, reading on instant consumable product, to prevent the oxidation of sterol and stanol fatty acid esters, improving the taste, reading on instant modulating flavor (see SilfverbergT at ¶[14946] and ¶[14958]).
Further regarding instant claims 108, 112 and amounts, Silfverberg teaches the amount of biologically active peptide in the dairy product may be 0.5-25 mg / 100 g of product (see SilfverbergT at ¶[14957]). Converting to the instant units of mg/kg the prior art range becomes:
0.5
m
g
p
e
p
t
i
d
e
100
g
p
r
o
d
u
c
t
x
1000
g
p
r
o
d
u
c
t
k
g
p
r
o
d
u
c
t
=
5
m
g
/
k
g
25
m
g
p
e
p
t
i
d
e
100
g
p
r
o
d
u
c
t
x
1000
g
p
r
o
d
u
c
t
k
g
p
r
o
d
u
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t
=
250
m
g
/
k
g
5-250 mg/kg, which overlaps with instant 0.001-25 mg/kg.
Further regarding claims 109-110 and a milk product, Silfverberg teaches mixing with milk materials such as whole milk and skim milk (see SilfverbergT at ¶[14967]), reading on instant cow milk, or fermented dairy products such as yogurt (see SilfverbergT at ¶[14955]).
Therefore, it would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to arrive at the instantly claimed invention with a reasonable expectation of success in view of the prior art for at least the following reason(s):
Regarding a consumable milk product, per MPEP § 2143(I)(A), a prima facie case of obviousness exists for combining prior art elements according to known methods to yield predictable results. It would have been obvious to an artisan to incorporate a known small molecule peptide such as CAS# 1001920-27-9 (as taught by Suli-Vargha) into a known method for modulating flavor of a milk product (as taught by Silfverberg), because the prior art teaches the method is suitable for small molecule peptides (as taught by Silfverberg).
Regarding overlapping ranges, per MPEP §2144.05(I), in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). The prior art teaches a range (5-250 mg/kg) which significantly overlaps with instant (0.001-25 mg/kg). Accordingly an artisan could readily arrive at a concentration encompassed by the instant claims.
Furthermore, it is well-within the ordinary skill in art to select a known small molecule peptide for use in a known method comprising a small molecule peptide for the same purpose as taught by the prior art.
Therefore, an artisan would arrive at the same invention as presently claimed for reasons taught in the prior art.
Claim 102 is rejected under 35 U.S.C. 103 as being unpatentable over Nam as applied to claims 94-97, 99, 103, 106 above in view of Betts et. al.5
The prior art differs from the instant claims as follows: While Nam teaches CAS# 714272-02-3, CAS# 714272-02-3 differs from claim 102 in R2.
However,
CAS# 714272-02-3 R2 corresponds with an isoleucine residue, wherein R is a sec-butyl group. If the isoleucine residue were its structural isomer leucine, the structure would read on claim 102 because R2 would be
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, n2 would be 1 and G2 would be C3 alkyl.
Betts teaches isoleucine and leucine are both hydrophobic aliphatic amino acids (see Betts at p. 319), and are substitutable amino acids (see Betts at p. 321 “13.5.2 Isoleucine (Ile, I)” p. 322 “13.5.3 Leucine (Leu, L)”.
Therefore, it would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to arrive at the instantly claimed invention with a reasonable expectation of success in view of the prior art for at least the following reason(s):
Per MPEP § 2143(I)(B), a prima facie case of obviousness exists for simple substitution of one known element for another to obtain predictable results. It would have been obvious to an artisan to substitute the isoleucine residue of CAS# 714272-02-3 (as taught by Nam) with leucine to arrive at a compound wherein n2 is 1, because the prior art teaches they are exchangeable amino acids (as taught by Betts).
Furthermore, it is well-within the ordinary skill in art to incorporate leucine in lieu of isoleucine.
Therefore, an artisan would arrive at the same invention as presently claimed for reasons taught in the prior art.
Allowable Subject Matter
Claims 104-105 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
The closest prior art to claims 104-105 is U.S. Patent No. 5,369,094 to Schally et. al.6
Schally teaches bombesin antagonists to treat cancerous tumors (see Schally at title and col. 1 lines 19-21) such as
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also known as CAS# 163759-30-6 (see Schally at col. 9-10 Peptide No. 17 and at col. 6 “Nomenclature” and col. 4 lines 30-35).
CAS# 163759-30-6
Instant Claim 96 Formula 2o
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CAS# 163759-30-6 correlates with formula 2o of claim 96 when X is CH2, Rr is
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102
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, n is 1, Gr is C6-10 aryl specifically phenyl, R1 is
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, n1 is 1, G1 is C1-10 heteroaryl specifically indole, in other words R1 is
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120
104
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, R2 is
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, n2 is 1, G2 is H.
Schally teaches compositions comprising the disclosed peptides and a carrier (see Schalley at claim 14). Schally teaches a method of administering an effective dose of a disclosed peptide (see Schalley at claim 15).
The prior art differs from the instant claims as follows: While Schally teaches CAS# 163759-30-6, CAS# 163759-30-6 differs from the instantly claimed genus in Rt. Instant Rt may be A3-A4-A5-A6-Rt*, but CAS# 163759-30-6 has an extra amino acid: A3 is valine, A4 is glycine, A5 is histidine, A6 is psi-leucine, “A7” is thiazolidine, Rt* is NH2.
Schally does not suggest omitting an amino acid from the peptide sequence, or altering the location of the histidine residue. An artisan would thus not be motivated to alter CAS# 163759-30-6 to arrive at a species of instant claim 104 or 105.
Conclusion
Claims 94-103, 106-113 are rejected.
Claims 104-105 are objected to.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SOPHIA J REILLY whose telephone number is (703)756-5669. The examiner can normally be reached 9:00 am - 5:00 pm EST M-F.
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/SOPHIA REILLY/Examiner, Art Unit 1627
1 Cite No. 4 in the IDS filed 11/19/24. Suli-Vargha et. al. "1,4-Diazepine-2,5-dione ring formation during solid phase synthesis of peptides containing aspartic acid β-benzyl ester" J. Pept. Sci. 2007, 13, 742-748. DOI:10.1002/psc.885
2 Nam et. al. "Conformationally Constrained Peptide Analogues of pTyr-Glu-Glu-Ile as Inhibitors of the Src SH2 Domain Binding" J. Med. Chem. 2004, 47, 3131-3141. DOI: 10.1021/jm040008+. Hereinafter Nam.
3 Neuberger et. al. "Stereochemistry of Amino Acids" Advances in Protein Chemistry Vol. 4; Academic Press, 1948; pp. 297-383. DOI: 10.1016/S0065-3233(08)60009-1. Hereinafter Neuberger.
4 Published August 18, 2011. Hereinafter Silfverberg. Machine Translation of FI 122054 B, Translated by Patent Translate Espacenet.org on 10/6/26, 24 pages, hereinafter SilfverbergT.
5 Betts et. al. "Chapter 13 Amino-Acid Properties and Consequences of Substitutions" in Bioinformatics for Geneticists: A Bioinformatics Primer for the Analysis of Genetic Data John Wiley & Sons 2007, pp. 311-342. ISBN 9780470059173. Hereinafter Betts.
6 Patented November 29, 1994. Hereinafter Schally.
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