DETAILED ACTION
Status of Claims
Claims 1, 3, 8-11, 13-18, 20, 22, 76, 140 and 146-149 are currently pending. Claims 1, 3, 8-11, 13-18, 20, 22 and 76 are currently under consideration and are the subject of this Office Action. This is the first Office Action on the merits of the claims. Non-elected claims 140 and 146-149 are withdrawn from consideration. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of Office Action: Non-Final.
Election/Restrictions
Applicant’s election of the claims of Group I (claims 1, 3, 8-11, 13-18, 20, 22 and 76) in the response filed on June 03, 2026 (to the December 03, 2025 Requirement for Restriction) is acknowledged. In response to applicant’s election, the claims of Group II (claims 140 and 146-149) are withdrawn from further consideration pursuant to 37 C.F.R. § 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant has elected the claims of Group I without traverse.
Accordingly, the December 03, 2025 Requirement for Restriction is made FINAL, and claims 1, 3, 8-11, 13-18, 20, 22 and 76 are examined as follows.
Claim Objections
The following claims are objected to because of the following informalities:
A. Claim 1 is objected because the claim should read:
1. ([…]) A polymer of the formula:
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wherein:
R1 is hydrogen, alkyl(C≤12), cycloalkyl(C≤12), substituted alkyl(C≤12), substituted cycloalkyl(C≤12), [[or]]
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, or a metal chelating group;
n is an integer from 1 to 500;
R2 and R2′ are each independently selected from hydrogen, alkyl(C≤12), cycloalkyl(C≤12), substituted alkyl(C≤12), or substituted cycloalkyl(C≤12);
R3 is a group of the formula:
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wherein:
nx is 1 to[[-]] 10;
X1, X2, and X3 are each independently selected from hydrogen, alkyl(C≤12), cycloalkyl(C≤12), substituted alkyl(C≤12), or substituted cycloalkyl(C≤12); and
X4 and X5 are each independently selected from alkyl(C≤12), cycloalkyl(C≤12), aryl(C≤12), heteroaryl(C≤12) or a substituted version of any of these groups, or X4 and X5 are taken together and are alkanediyl(C≤12), alkoxydiyl(C≤12), alkylaminodiyl(C≤12), or a substituted version of any of these groups;
x is an integer from 1 to 150;
R4 is a group of the formula:
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wherein:
ny is 1 to[[-]] 10;
X1′, X2′, and X3′ are each independently selected from hydrogen, alkyl(C≤12), cycloalkyl(C≤12), substituted alkyl(C≤12), or substituted cycloalkyl(C≤12); and
X4′ and X5′ are each independently selected from alkyl(C≤12), cycloalkyl(C≤12), aryl(C≤12), heteroaryl(C≤12) or a substituted version of any of these groups, or X4′ and X5′ are taken together and are alkanediyl(C≤12), alkoxydiyl(C≤12), alkylaminodiyl(C≤12), or a substituted version of any of these groups;
y is an integer from 1 to 150;
R5 is a group of the formula:
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wherein:
nz is 1 to[[-]] 10;
Y1, Y2, and Y3 are each independently selected from hydrogen, alkyl(C≤12), cycloalkyl(C≤12), substituted alkyl(C≤12), or substituted cycloalkyl(C≤12); and
Y4 is hydrogen, alkyl(C≤12), acyl(C≤12), substituted alkyl(C≤12), substituted acyl(C≤12), a dye, or a fluorescence quencher;
z is an integer from 0 to[[-]] 6; and
R6 is hydrogen, halo, hydroxy, alkyl(C≤12), or substituted alkyl(C≤12),
wherein R3, R4, and R5 can occur in any order within the polymer, provided that R3 and R4 are not the same group.
Further, formulas (II), (III) and (IV) must be amended to clearly depict “nx,” “ny” and “nz.,” NOT “nx, “ny” and “nz.””
B. Claim 3 is objected to because the claim should read:
3. ([…]) The polymer of claim 1, further defined by the formula wherein:
R1 is hydrogen, alkyl(C≤8), substituted alkyl(C≤8), [[or]]
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, or a metal chelating group;
n is an integer from 10 to 200;
R2 and R2′ are each independently selected from hydrogen, alkyl(C≤8), or substituted alkyl(C≤8);
R3 is a group of the formula:
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wherein:
X1, X2, and X3 are each independently selected from hydrogen, alkyl(C≤8), or substituted alkyl(C≤8); and
X4 and X5 are each independently selected from alkyl(C≤12), aryl(C≤12), heteroaryl(C≤12) or a substituted version of any of these groups, or X4 and X5 are taken together and are alkanediyl(C≤8) or substituted alkanediyl(C≤8);
x is an integer from 1 to 100;
R4 is a group of the formula:
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wherein:
X1′, X2′, and X3′ are each independently selected from hydrogen, alkyl(C≤8), or substituted alkyl(C≤8); and
X4′ and X5′ are each independently selected from alkyl(C≤12), aryl(C≤12), heteroaryl(C≤12) or a substituted version of any of these groups, or X4′ and X5′ are taken together and are alkanediyl(C≤8) or substituted alkanediyl(C≤8);
y is an integer from 1 to 100;
R5 is a group of the formula:
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wherein:
Y1, Y2, and Y3 are each independently selected from hydrogen, alkyl(C≤8), substituted alkyl(C≤8); and
Y4 is hydrogen, a dye, or a fluorescence quencher;
z is an integer from 0 to[[-]] 6; and
R6 is hydrogen, halo, alkyl(C≤6), or substituted alkyl(C≤6),
wherein R3, R4, and R5 can occur in any order within the polymer, provided that R3 and R4 are not the same group.
C. Claim 8 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all the limitations of the base claim and any intervening claims.
D. Claim 9 is objected to because the claim should read:
9. ([…]) The polymer according to claim 1, wherein R1 is a metal chelating group selected from 1,4,7,10-tetraazacyclododecane-tetraacetic acid (DOTA), 1,4,8,11-tetraazacyclotetradecane-1,4,8,11-tetraacetic acid, (TETA), 1,8-Diamino-3,6,10,13,16,19-hexaazabicyclo[6,6,6]-eicosane (Diamsar), 1,4,7-triazacyclononane-triacetic acid (NOTA), {4-[2-(bis-carboxymethylamino)-ethyl]-7-carboxymethyl-[1,4,7]triazonan-1-yl}-acetic acid (NETA), N,N′,N″, tris(2-mercaptoethyl)-1,4,7-triazacyclononane (TACN-TM), diethylenetriaminepentaacetic acid (DTPA), 1,4,7-triazacyclononane-1,4,7-tris[methyl(2-carboxyethyl)phosphinic acid] (TRAP), 1,4,7-triazacyclononane-1,4-bis[methylene(hydroxymethyl)phosphinic acid]-7-[methylene(2-carboxyethyl)phosphinic acid] (NOPO), 1,4-bis(carboxymethyl)-6-[bis(carboxymethyl)]amino-6-methylperhydro-1,4-diazepine (AAZTA), 2,2′-(6-((carboxymethyl)amino)-1,4-diazepane-1,4-diyl)diacetic acid (DATA), N,N′-bis(2-hydroxybenzyl)-ethylenediamine-N,N′-diacetic acid, (HBED), N,N′-bis(2-hydroxy-5-sulfobenzyl)-ethylenediamine-N,N′-diacetic acid (SHBED), bis(2-pyridylcarbonyl) amine (BPCA), 4-acetylamino-4-[2-[(3-hydroxy-1,6-dimethyl-4-oxo-1,4-dihydro-pyridin-2-ylmethyl)-carbamoyl]-ethyl]-heptanedioicacid bis-[(3-hydroxy-1,6-dimethyl-4-oxo-1,4-dihydro-pyridin-2-ylmethyl)-amide] (CP256), desferrioxamine B (DFO), 3,6,9,15-tetraazabicyclo[9.3.1]-pentadeca-1(15),11,13-triene-3,6,9,-triacetic acid (PCTA), 1,4,7,10,13,16-hexaazacyclohexadecane-N,N′,N″,N′″,N″″,N″″″-hexaacetic acid (HEHA), 1,4,7,10,13-pentaazacyclopentadecane-N,N′,N″,N′″,N″″-pentaacetic acid (PEPA), or a derivative thereof.
but would be allowable if rewritten in independent form including all the limitations of the base claim and any intervening claims, and addressing the above-noted objection, and amendments overcoming the rejection under 35 U.S.C. 112 (b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, set forth in this Office action.
E. Claim 10 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all the limitations of the base claim and any intervening claims, and with amendments overcoming the rejection under 35 U.S.C. 112 (b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, set forth in this Office action.
F. Claim 11 is objected to because the claim should read:
11. (Original) The polymer of claim 8, wherein the nitrogen containing macrocycle is a compound of the formula:
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wherein:
R7, R8, R9, R10, R7′, R8′, and R9′ are each independently selected from hydrogen, alkyl(C≤12), acyl(C≤12), -alkanediyl(C≤12)-acyl(C≤12), or a substituted version of any of these groups; or a linker, wherein the linker is an alkanediyl(C≤12)-C(O)NH— or a substituted alkanediyl(C≤12)-C(O)NH—; [[or]]
R7 is taken together with one of R8, R9, or R10 and is alkanediyl(C≤6); [[or]]
R8 is taken together with one of R7, R9, or R10 and is alkanediyl(C≤6); [[or]]
R9 is taken together with one of R7, R8, or R10 and is alkanediyl(C≤6); [[or]]
R10 is taken together with one of R7, R8, or R9 and is alkanediyl(C≤6); [[or]]
R7′ is taken together with one of R8′ or R9′ and is alkanediyl(C≤6); [[or]]
R8′ is taken together with one of R7′ or R9′ and is alkanediyl(C≤6); [[or]]
R9′ is taken together with one of R7′ or R8′ and is alkanediyl(C≤6); and
a, b, c, d, a′, b′, and c′ are each independently selected from 1, 2, 3, or 4.
Further, formulas (VA)) and (VB) must be amended to properly orient “a, b, c, d, a′, b′, and c′,” but would be allowable if rewritten in independent form including all the limitations of the base claim and any intervening claims, and addressing the above-noted objection, and amendments overcoming the rejection under 35 U.S.C. 112 (b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, set forth in this Office action.
G. Claim 8 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all the limitations of the base claim and any intervening claims, and with amendments overcoming the rejection under 35 U.S.C. 112 (b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, set forth in this Office action.
H. Claim 13 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all the limitations of the base claim and any intervening claims, and with amendments overcoming the rejection under 35 U.S.C. 112 (b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, set forth in this Office action.
I. Claim 14 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all the limitations of the base claim and any intervening claims, and with amendments overcoming the rejection under 35 U.S.C. 112 (b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, set forth in this Office action.
J. Claim 15 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all the limitations of the base claim and any intervening claims, and with amendments overcoming the rejection under 35 U.S.C. 112 (b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, set forth in this Office action.
K. Claim 16 is objected to because the claim should read:
16. (Original) The polymer of claim 14, wherein the metal ion is suitable for positron emission tomography (PET) imaging or single-photon emission computerized technology (SPECT) imaging.
but would be allowable if rewritten in independent form including all the limitations of the base claim and any intervening claims, and addressing the above-noted objection.
L. Claim 17 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all the limitations of the base claim and any intervening claims, and with amendments overcoming the rejection under 35 U.S.C. 112 (b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, set forth in this Office action.
M. Claim 18 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all the limitations of the base claim and any intervening claims, and with amendments overcoming the rejection under 35 U.S.C. 112 (b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, set forth in this Office action.
N. Claim 20 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all the limitations of the base claim and any intervening claims, and with amendments overcoming the rejection under 35 U.S.C. 112 (b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, set forth in this Office action.
O. Claim 22 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all the limitations of the base claim and any intervening claims, and with amendments overcoming the rejection under 35 U.S.C. 112 (b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, set forth in this Office action.
Appropriate correction is required.
Claim Rejections – 35 U.S.C. § 112 - Indefiniteness
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.
Claims 1, 3, 8-11, 13-18, 20, 22 and 76 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 pre-AIA , that applicant regards as the invention.
Claim 1 is drawn to:
1. ([…]) A polymer of the formula:
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wherein:
[…];
R3 is a group of the formula:
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wherein:
nx is 1-10;
[…];
x is an integer from 1 to 150;
R4 is a group of the formula:
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wherein:
ny is 1-10;
[…];
y is an integer from 1 to 150;
R5 is a group of the formula:
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wherein:
[…];
z is an integer from 0-6; and
R6 is hydrogen, halo, hydroxy, alkyl(C≤12), or substituted alkyl(C≤12),
wherein R3, R4, and R5 can occur in any order within the polymer, provided that R3 and R4 are not the same group.
wherein the recitation, “wherein R3, R4, and R5 can occur in any order within the polymer, provided that R3 and R4 are not the same group” renders the metes and bounds of the claim unclear, because this recitation suggests that “R3, R4, and R5,” but the scope of “R5,” for “(R5)z” in Formula (I) wherein “z is an integer from 0-6,” encompasses an embodiment not requiring “(R5)z.” Therefore, it is unclear whether or not “R5” is required. In this regard, it is noted that the Board has held: “if a claim is amenable to two or more plausible claim constructions, the USPTO is justified in requiring the applicant to more precisely define the metes and bounds of the claimed invention by holding the claim unpatentable under 35 U.S.C. §112, second paragraph, as indefinite.” Ex parte Miyazaki, 89 USPQ2d 1207, 1211 (BPAI 2008) (expanded panel). Subsequent claims 3, 8-11, 13-18, 20, 22 and 76 depend on claim 1 and are thus, indefinite as well.
Further clarification is required.
Claim Rejections – 35 U.S.C. § 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.
Claims 1, 3 and 76 are rejected under 35 U.S.C. § 102(a)(1) as being anticipated by GAO (WO 2012/039741 A1, Publ. Mr. 29, 2012; on 02/07/2024 IDS; hereinafter, “Gao”).
Gao is directed to:
Title: NOVEL BLOCK COPOLYMER AND MICELLE COMPOSITIONS AND METHODS OF USE THEREOF
Abstract: Provided herein are block copolymers comprising a hydrophilic polymer segment and a hydrophobic polymer segment, wherein the hydrophilic polymer segment comprises a polymer selected from the group consisting of: poly(ethylene oxide) (PEO), poly(methacrylate phosphatidyl choline) (MPC), and polyvinylpyrrolidone (PVP), wherein the hydrophobic polymer segment comprises wherein R' is -H or -CH3, wherein R is -NR1R2, wherein R1 and R2 are alkyl groups, wherein R1 and R2 are the same or different, wherein R1 and R2 together have from 5 to 16 carbons, wherein R1 and R2 may optionally join to form a ring, wherein n is 1 to about 10, and wherein x is about 20 to about 200 in total. Also provided are pH-sensitive micelle compositions for therapeutic and diagnostic applications.
Gao, title & abstract. In this regard, Gao teaches a “block copolymer comprising a hydrophilic polymer segment and a hydrophobic polymer segment” that “comprises a compound of Formula I”:
SUMMARY OF THE INVENTION
[0011] In one aspect of the invention is a block copolymer comprising a hydrophilic polymer segment and a hydrophobic polymer segment, wherein the hydrophilic polymer segment comprises a polymer selected from the group consisting of: poly(ethylene oxide) (PEO), poly(methacrylate phosphatidyl choline) (MPC), and polyvinylpyrrolidone (PVP), wherein the hydrophobic polymer segment comprises
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wherein R' is -H or -CH3, wherein R is -NR'R2, wherein R1 and R2 are alkyl groups, wherein R1 and R2 are the same or different, wherein R1 and R2 together have from 5 to 16 carbons, wherein R1 and R2 may optionally join to form a ring, wherein n is 1 to about 10, wherein x is about 20 to about 200 in total, and wherein the block copolymer optionally comprises a labeling moiety. In some embodiments, the hydrophilic polymer segment comprises PEO. In some embodiments, n is 1 to 4. In some embodiments, n is 2. In some embodiments, R' is -CH3. In some embodiments, R' is -H. In some embodiments, x is about 40 to about 100 in total. In some embodiments, x is about 50 to about 100 in total. In some embodiments, x is about 40 to about 70 in total. In some embodiments, x is about 60 to about 80 in total. In some embodiments, x is 1 about 70 in total. In some embodiments, R1 and R2 are each straight or branched alkyl. In some embodiments, R1 and R2 join to form a ring. In some embodiments, R1 and R2 are the same. In some embodiments, R1 and R2 are different. In some embodiments, R1 and R2 each have 3 to 8 carbons. In some embodiments, R1 and R2 together form a ring having 5 to 10 carbons. In some embodiments, R1 and R2 are propyl. In some embodiments, propyl is iso-propyl. In some embodiments, R1 and R2 are butyl. In some embodiments, butyl is n-butyl. In some embodiments, R1 and R2 together are -(CH2)5-. In some embodiments, R1 and R9 together are - (CH2)6-. In some embodiments, the block copolymer comprises a compound of Formula I:
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(Formula I)
wherein L is a labeling moiety, wherein y is 0 to about 6, wherein R" is -H or -CH3; wherein m is 1 to about 10; wherein z is such that the PEO is about 2 kD to about 20 kD in size, wherein R'" is an suitable moiety, and wherein the following portion of the structure:
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may be arranged in any order. In some embodiments, R" is -CH3. In some embodiments, R" is - H. In some embodiments, m is 1 to 4. In some embodiments, m is 2. In some embodiments, the PEO is about 2 kD to about 10 kD in size. In some embodiments, the PEO is about 4 kD to about 6 kD in size. In some embodiments, the PEO is about 5 kD in size. In some embodiments, z is about 114. In some embodiments, y is 0. In some embodiments, y is 1 to 6. In some embodiments, y is about 3. In some embodiments, L is a fluorescent label. In some embodiments, the fluorescent label is tetramethyl rhodamine (TMR). In some embodiments, L is a near-infrared (NIR) label. In some embodiments, the NIR label is cypate. In some embodiments, the NIR label is a cypate analog. In some embodiments, R'" is an end group resulting from a polymerization reaction. In some embodiments, R" ' is Br. In some embodiments, R'" is thiolate. In some embodiments, R'" is a thioester. In some embodiments, the following portion of the structure:
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is randomized. In some embodiments, the block copolymer forms a pH-sensitive micelle.
Gao, par. [0011].
Regarding independent claim 1 and the requirements:
1. (Original) A polymer of the formula:
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wherein:
R1 is hydrogen, alkyl(C≤12), cycloalkyl(C≤12), substituted alkyl(C≤12), substituted cycloalkyl(C≤12), or
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, or a metal chelating group;
n is an integer from 1 to 500;
R2 and R2′ are each independently selected from hydrogen, alkyl(C≤12), cycloalkyl(C≤12), substituted alkyl(C≤12), or substituted cycloalkyl(C≤12);
R3 is a group of the formula:
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wherein:
nx is 1-10;
X1, X2, and X3 are each independently selected from hydrogen, alkyl(C≤12), cycloalkyl(C≤12), substituted alkyl(C≤12), or substituted cycloalkyl(C≤12); and
X4 and X5 are each independently selected from alkyl(C≤12), cycloalkyl(C≤12), aryl(C≤12), heteroaryl(C≤12) or a substituted version of any of these groups, or X4 and X5 are taken together and are alkanediyl(C≤12), alkoxydiyl(C≤12), alkylaminodiyl(C≤12), or a substituted version of any of these groups;
x is an integer from 1 to 150;
R4 is a group of the formula:
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wherein:
ny is 1-10;
X1′, X2′, and X3′ are each independently selected from hydrogen, alkyl(C≤12), cycloalkyl(C≤12), substituted alkyl(C≤12), or substituted cycloalkyl(C≤12); and
X4′ and X5′ are each independently selected from alkyl(C≤12), cycloalkyl(C≤12), aryl(C≤12), heteroaryl(C≤12) or a substituted version of any of these groups, or X4′ and X5′ are taken together and are alkanediyl(C≤12), alkoxydiyl(C≤12), alkylaminodiyl(C≤12), or a substituted version of any of these groups;
y is an integer from 1 to 150;
R5 is a group of the formula:
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wherein:
nz is 1-10;
Y1, Y2, and Y3 are each independently selected from hydrogen, alkyl(C≤12), cycloalkyl(C≤12), substituted alkyl(C≤12), or substituted cycloalkyl(C≤12); and
Y4 is hydrogen, alkyl(C≤12), acyl(C≤12), substituted alkyl(C≤12), substituted acyl(C≤12), a dye, or a fluorescence quencher;
z is an integer from 0-6; and
R6 is hydrogen, halo, hydroxy, alkyl(C≤12), or substituted alkyl(C≤12),
wherein R3, R4, and R5 can occur in any order within the polymer, provided that R3 and R4 are not the same group.
Gao clearly teaches a “block copolymer comprising a hydrophilic polymer segment and a hydrophobic polymer segment” that “comprises a compound of Formula I” (Gao, par. [0011]), reading on the polymer of the formula (I) of claim 1 with respect to “R1, ” “R2” and “R2’ ” “(R3)x,” “(R4)y” and “R6,” as well as the requirements of claim 3 for:
3. ([…]) The polymer of claim 1, further defined by the formula wherein:
R1 is hydrogen, alkyl(C≤8), substituted alkyl(C≤8), or
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, or a metal chelating group;
n is an integer from 10 to 200;
R2 and R2′ are each independently selected from hydrogen, alkyl(C≤8), or substituted alkyl(C≤8);
R3 is a group of the formula:
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wherein:
X1, X2, and X3 are each independently selected from hydrogen, alkyl(C≤8), or substituted alkyl(C≤8); and
X4 and X5 are each independently selected from alkyl(C≤12), aryl(C≤12), heteroaryl(C≤12) or a substituted version of any of these groups, or X4 and X5 are taken together and are alkanediyl(C≤8) or substituted alkanediyl(C≤8);
x is an integer from 1 to 100;
R4 is a group of the formula:
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wherein:
X1′, X2′, and X3′ are each independently selected from hydrogen, alkyl(C≤8), or substituted alkyl(C≤8); and
X4′ and X5′ are each independently selected from alkyl(C≤12), aryl(C≤12), heteroaryl(C≤12) or a substituted version of any of these groups, or X4′ and X5′ are taken together and are alkanediyl(C≤8) or substituted alkanediyl(C≤8);
y is an integer from 1 to 100;
R5 is a group of the formula:
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wherein:
Y1, Y2, and Y3 are each independently selected from hydrogen, alkyl(C≤8), substituted alkyl(C≤8); and
Y4 is hydrogen, a dye, or a fluorescence quencher;
z is an integer from 0-6; and
R6 is hydrogen, halo, alkyl(C≤6), or substituted alkyl(C≤6),
wherein R3, R4, and R5 can occur in any order within the polymer, provided that R3 and R4 are not the same group.
In this regard, it is further noted that Gao’s formula (I) (Gao, par. [0011]) reads on the requirement of claim 1 for wherein “z” for “(R5)z” is 0, whereby the provision, “wherein R3, R4, and R5 can occur in any order within the polymer, provided that R3 and R4 are not the same group” (of claims 1 and 3), is interpreted as not required in the absence of “(R5)z.”
Thus, Gao anticipates claims 1 and 3.
Regarding claim 76 and the requirements:
76. ([…]) A micelle of a polymer according to claim 1.
Gao teaches “[t]he ionizable groups may act as tunable hydrophilic/hydrophobic blocks at different pH values, which may directly affect the dynamic self-assembly of micelles,” wherein “[d]ifferent block copolymers may be selected to provide micelles having different transition pH values within physiological range, in order to achieve selective activation within various environments, such as tumors (e.g. the extracellular environment of tumors), or within specific endocytic compartments such as early or late endosomes or lysosomes” (Gao, [0026] & [0048], and Fig. 1C).
Thus, Gao anticipates claim 76.
Claim Rejections – 35 U.S.C. § 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under pre-AIA 35 U.S.C. § 103(a) 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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 C.F.R. § 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. § 102(b)(2)(C) for any potential 35 U.S.C. § 102(a)(2) prior art against the later invention.
Claims 1, 3 and 76 are rejected under 35 U.S.C. § 103 as being unpatentable over GAO (WO 2012/039741 A1, Publ. Mr. 29, 2012; on 02/07/2024 IDS; hereinafter, “Gao”).
Gao is directed to:
Title: NOVEL BLOCK COPOLYMER AND MICELLE COMPOSITIONS AND METHODS OF USE THEREOF
Abstract: Provided herein are block copolymers comprising a hydrophilic polymer segment and a hydrophobic polymer segment, wherein the hydrophilic polymer segment comprises a polymer selected from the group consisting of: poly(ethylene oxide) (PEO), poly(methacrylate phosphatidyl choline) (MPC), and polyvinylpyrrolidone (PVP), wherein the hydrophobic polymer segment comprises wherein R' is -H or -CH3, wherein R is -NR1R2, wherein R1 and R2 are alkyl groups, wherein R1 and R2 are the same or different, wherein R1 and R2 together have from 5 to 16 carbons, wherein R1 and R2 may optionally join to form a ring, wherein n is 1 to about 10, and wherein x is about 20 to about 200 in total. Also provided are pH-sensitive micelle compositions for therapeutic and diagnostic applications.
Gao, title & abstract. In this regard, Gao teaches a “block copolymer comprising a hydrophilic polymer segment and a hydrophobic polymer segment” that “comprises a compound of Formula I.” Gao, par. [0011].
Regarding independent claim 1, Gao clearly teaches a “block copolymer comprising a hydrophilic polymer segment and a hydrophobic polymer segment” that “comprises a compound of Formula I” (Gao, par. [0011]), relating to the polymer of the formula (I) of claim 1 with respect to “R1, ” “R2” and “R2’ ” and “R6. However, Gao DOES NOT EXPRESSLY TEACH the particular arrangement of the “(R3)x,” “(R4)y” and “(R5)z” blocks of formula (I), “wherein R3, R4, and R5 can occur in any order within the polymer, provided that R3 and R4 are not the same group,” of claim 1, as well as the similar requirements of claim 3, which are well within the purview of the ordinarily skilled artisan, in light of Gao’s broader disclosure.
It is noted that a reference is analyzed using its broadest teachings. MPEP § 2123 [R-5] states: “[W]hen a patent simply arranges old elements with each performing the same function it had been known to perform and yields no more than one would expect from such an arrangement, the combination is obvious.” KSR v. Teleflex, 127 S.Ct. 1727, 1740 (2007)(quoting Sakraida v. A.G. Pro, 425 U.S. 273, 282 (1976). “[W]hen the question is whether a patent claiming the combination of elements of prior art is obvious”, the relevant question is “whether the improvement is more than the predictable use of prior art elements according to their established functions.” (Id.). Addressing the issue of obviousness, the Supreme Court noted that the analysis under 35 USC 103 “need not seek out precise teachings directed to the specific subject matter of the challenged claim, for a court can take account of the inferences and creative steps that a person of ordinary skill in the art would employ.” KSR v. Teleflex, 127 S.Ct. 1727, 1741 (2007). The Court emphasized that “[a] person of ordinary skill is… a person of ordinary creativity, not an automaton.” Id. at 1742. In this regard, Gao discloses hydrophobic segments related to the “(R3)x,” “(R4)y” and “(R5)z” blocks of formula (I) of claims 1 and 3, which contain “R” and “L” moieties that “may be arranged in any order,” e.g., “randomized,” or wherein “the R containing moieties may be present as a single block, with the L containing moieties present as a single block either preceding or following the R containing moieties,” while further contemplating that “[o]ther arrangements may also be utilized”:
Block Co-Polymer Compounds
[0064] Novel block copolymers are provided herein, comprising a hydrophilic polymer segment and a hydrophobic polymer segment, wherein the hydrophilic polymer segment comprises a polymer selected from the group consisting of: poly(ethylene oxide) (PEO), poly(methacrylate phosphatidyl choline) (MPC), and polyvinylpyrrolidone (PVP), wherein the hydrophobic polymer segment comprises
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wherein R' is -H or -CH3, wherein R is -NR1R2, wherein R1 and R2 are alkyl groups, wherein R1 and R2 are the same or different, wherein R1 and R2 together have from 5 to 16 carbons, wherein R1 and R2 may optionally join to form a ring, wherein n is 1 to about 10, wherein x is about 20 to about 200 in total, and wherein the block copolymer may further optionally comprise a labeling moiety. For example, x may be about 20 to about 200 as a continuous segment (i.e. a continuous segment of about 20 to about 200 monomer units), or other moieties (e.g. moieties comprising a label) may be interspersed between the monomer units, for example as described in more detail below.
[0065] Block copolymers of the invention include, for example, compounds of Formula I:
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(Formula I) wherein L is a labeling moiety, wherein y is 0 to about 6, wherein R" is -H or -CH3; wherein m is 1 to about 10, wherein z is such that the PEO is about 2 kD to about 20 kD in size, wherein x, n, R, and R' are as defined above, wherein R" ' is any suitable moiety, and wherein the following portion of the structure:
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may be arranged in any order.
[…]
[0067] In some embodiments, the following portion of the structure:
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is randomized, i.e.:
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wherein r indicates a random ordering of the R containing moieties and the L containing moieties (i.e. the R containing moieties and the L containing moieties are randomly interspersed).
[0068] In some embodiments, the following portion of the structure:
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is arranged sequentially. For example, the R containing moieties may be present as a single block, with the L containing moieties present as a single block either preceding or following the R containing moieties. Other arrangements may also be utilized.
Gao, par. [0064]-[0065] & [0067]-[0068]. Further in this regard, Gao teaches that “[t]he ionizable groups may act as tunable hydrophilic/hydrophobic blocks at different pH values, which may directly affect the dynamic self-assembly of micelles,” wherein “[d]ifferent block copolymers may be selected to provide micelles having different transition pH values within physiological range, in order to achieve selective activation within various environments, such as tumors (e.g. the extracellular environment of tumors), or within specific endocytic compartments such as early or late endosomes or lysosomes”:
[0026] Figure 1C illustrates the design principle of an example of a micelle comprising a fluorescent label (using TMR as an example). At high pH, micelle assembly results in fluorescence quenching due to homoFRET and photoinduced electron transfer (PET) mechanisms. At low pH, micelle disassembly leads to dramatic increase in emission. At high pH, the amine in the hydrophobic polymer segment is not protonated. At low pH, the amine group in the hydrophobic polymer segment is protonated.
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[…]
DETAILED DESCRIPTION OF THE INVENTION
[0048] The present invention provides block copolymers and micelle compositions comprising one or more of said block copolymers that are useful in one or more therapeutic and/or diagnostic applications, such as treatment of cancer, cardiovascular disease, inflammation, an autophagy-related disease, or lysosomal storage disease, tumor imaging, and/or imaging of intracellular organelles such as early endosomes, late endosomes and lysosomes. The invention further provides methods for using the micelle compositions in such therapeutic and diagnostic applications. [0049] The block copolymers of the invention comprise a hydrophilic polymer segment and a hydrophobic polymer segment, wherein the hydrophobic polymer segment comprises an ionizable amine group to render pH sensitivity. The block copolymers form pH-activatable micellar (pHAM) nanoparticles based on the supramolecular self-assembly of these ionizable block copolymers (see e.g. Figure 1C). For example, Figure 1C illustrates the design principle of a non-limiting example of a micelle of the invention. At higher pH, the block copolymers assemble into micelles, whereas at lower pH, ionization of the amine group in the hydrophobic polymer segment results in dissociation of the micelle. Without wishing to be bound by theory, micelle formation and its thermodynamic stability are driven by the delicate balance between the hydrophobic and hydrophilic segments. The ionizable groups may act as tunable hydrophilic/hydrophobic blocks at different pH values, which may directly affect the dynamic self-assembly of micelles. Without wishing to be bound by theory, micellization may sharpen the ionization transition of the amines in the hydrophobic polymer segment, rendering fast and ultra-sensitive pH response. Different block copolymers may be selected to provide micelles having different transition pH values within physiological range, in order to achieve selective activation within various environments, such as tumors (e.g. the extracellular environment of tumors), or within specific endocytic compartments such as early or late endosomes or lysosomes.
(Gao, [0026] & [0048], and Fig. 1C). Therefore, Gao teaches a range of embodiments, wherein hydrophobic segments containing “R” and “L” moieties “may be arranged in any order,” for which it is noted that MPEP § 2144.05 (I), states, “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).” Further in this respect, it is noted, “[w]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955); and also MPEP § 2144.05(II)(A). In the instant case, the arrangement of Gao’s hydrophobic segments containing “R” and “L” moieties is clearly a result-effective variable, which Gao teaches that “[t]he ionizable groups may act as tunable hydrophilic/hydrophobic blocks at different pH values, which may directly affect the dynamic self-assembly of micelles” for “different transition pH values within physiological range, in order to achieve selective activation within various environments.” Gao, [0026] & [0048], and Fig. 1C. Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date to optimize the hydrophobic segments containing “R” and “L” moieties (Gao, par. [0064]-[0065] & [0067]-[0068]) for “different pH values, which may directly affect the dynamic self-assembly of micelles” (Gao, [0026] & [0048], and Fig. 1C) in order to obtain the particular arrangement of the “(R3)x,” “(R4)y” and “(R5)z” blocks of formula (I), “wherein R3, R4, and R5 can occur in any order within the polymer, provided that R3 and R4 are not the same group,” of claims 1 and 3, absent evidence to the contrary.
Thus, Gao renders claims 1 and 3 obvious.
Regarding claim 76 and the requirements:
76. ([…]) A micelle of a polymer according to claim 1.
Gao teaches “[t]he ionizable groups may act as tunable hydrophilic/hydrophobic blocks at different pH values, which may directly affect the dynamic self-assembly of micelles,” wherein “[d]ifferent block copolymers may be selected to provide micelles having different transition pH values within physiological range, in order to achieve selective activation within various environments, such as tumors (e.g. the extracellular environment of tumors), or within specific endocytic compartments such as early or late endosomes or lysosomes” (Gao, [0026] & [0048], and Fig. 1C).
Thus, Gao renders claim 76 obvious.
Claim Rejections - Nonstatutory Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory obviousness-type double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); and In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on a nonstatutory double patenting ground provided the conflicting application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement.
Effective January 1, 1994, a registered attorney or agent of record may sign a terminal disclaimer. A terminal disclaimer signed by the assignee must fully comply with 37 CFR 3.73(b).
Claims 1, 3 and 76 are rejected on the ground of nonstatutory double patenting over claims 1-13 of US 10,098,971 B2 to Gao et al. (hereinafter “‘971 Patent,” matured from copending Application No. 15/369,701).
Although the conflicting claims are not identical, they are not patentably distinct because the instant claims as well as the copending claims recite polymers that overlap in scope:
independent claim 1 of the ‘971 Patent is drawn to a polymer of the structure:
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wherein R1 is hydrogen, alkyl(C≤12),
wherein n is an integer from 10 to 200,
wherein R2 and R2’ are each independently methyl,
wherein nx is 1-3,
wherein X1 is a hydrogen or an alkyl(C≤12),
wherein X2, and X3 are each hydrogen, and
wherein x is an integer from 30 to 150
[...];
while independent claim 1 is drawn to a polymer of a similar structure.
:
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wherein R1 is hydrogen, alkyl(C≤12), cycloalkyl(C≤12), substituted alkyl(C≤12), substituted cycloalkyl(C≤12), or
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, or a metal chelating group,
wherein n is an integer from 1 to 500,
wherein R2 and R2’ are each independently selected from hydrogen, alkyl(C≤12), cycloalkyl(C≤12), substituted alkyl(C≤12), or substituted cycloalkyl(C≤12),
wherein nx is 1-10,
wherein x is an integer from 1 to 150
[...];
whereby claims 1-13 of the ‘971 Patent render instant claims 1, 3 and 76 obvious.
Claims 1, 3, 8 and 76 are rejected on the ground of nonstatutory double patenting over claims 1-18 of US 11,013,818 B2 to Gao et al. (hereinafter “‘818 Patent,” matured from copending Application No. 16/114,187).
Although the conflicting claims are not identical, they are not patentably distinct because the instant claims as well as the copending claims recite polymers that overlap in scope:
independent claim 1 of the ‘818 Patent is drawn to a polymer of the structure:
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wherein R1 is hydrogen, alkyl(C≤12), cycloalkyl(C≤12), substituted alkyl(C≤12), substituted cycloalkyl(C≤12), or
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, or a metal chelating group,
wherein n is an integer from 1 to 500,
wherein R2 and R2’ are each independently selected from hydrogen, alkyl(C≤12), cycloalkyl(C≤12), substituted alkyl(C≤12), or substituted cycloalkyl(C≤12),
wherein nx is 1-10,
wherein X1, X2, and X3 are each independently selected from hydrogen, alkyl(C≤12), cycloalkyl(C≤12), substituted alkyl(C≤12), or substituted cycloalkyl(C≤12),
wherein x is an integer from 1 to 150
[...];
while independent claim 1 is drawn to a polymer of a similar structure,
whereby claims 1-18 of the ‘818 Patent render claims 1, 3, 8 and 76 obvious.
Claims 1, 3, 8-11, 13-18, 20, 22 and 76 are rejected on the ground of nonstatutory double patenting over claims 1-19 of US 11,723,990 B2 to Gao et al. (hereinafter “‘990 Patent,” matured from copending Application No. 17/231,922).
Although the conflicting claims are not identical, they are not patentably distinct because the instant claims as well as the copending claims recite polymers that overlap in scope.
Claim 1 is anticipated by claims 1-5 of the ‘990 Patent.
Claim 3 is anticipated by claims 1-5 of the ‘990 Patent.
Claim 8 is anticipated by claim 7 of the ‘990 Patent.
Claim 9 is anticipated by claim 6 of the ‘990 Patent.
Claim 10 is anticipated by claim 8 of the ‘990 Patent.
Claim 11 is anticipated by claims 9-10 of the ‘990 Patent.
Claim 13 is anticipated by claim 11 of the ‘990 Patent.
Claim 14 is anticipated by claim 12 of the ‘990 Patent.
Claim 15 is anticipated by claim 13 of the ‘990 Patent.
Claim 16 is anticipated by claim 14 of the ‘990 Patent.
Claim 17 is anticipated by claim 15 of the ‘990 Patent.
Claim 18 is anticipated by claim 19 of the ‘990 Patent.
Claim 20 is anticipated by claims 16-17 of the ‘990 Patent.
Claim 22 is anticipated by claim 18 of the ‘990 Patent.
Conclusion
Claims 1, 3, 8-11, 13-18, 20, 22 and 76 are rejected. No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DOMINIC LAZARO whose telephone number is (571)272-2845. The examiner can normally be reached on Monday through Friday, 8:30am to 5:00pm EST; alternating Fridays out.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, BETHANY BARHAM can be reached on (571)272-6175. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/DOMINIC LAZARO/Primary Examiner, Art Unit 1611
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