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 .
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Claim Objections
Claim 16 is objected to because of the following informalities: the typos “responding” in lines 1, 5-6, 25, 28, and 35 should be “corresponding” or equivalent. Appropriate correction is required.
Claim 21 is objected to because of the following informalities: the typo “responding” in line 2 should be “corresponding” or equivalent. Appropriate correction is required.
Claim 22 is objected to because of the following informalities: the typo “responding” in line 4 should be “corresponding” or equivalent. Appropriate correction is required.
Claim 22 is objected to because of the following informalities: grammar in line 4 is not clear whether the polyethylene glycol group is in alternative to the functional group or the alkyl group. Appropriate correction is required.
Claim Interpretation
Claims 16, 21, and 22 recite the term “responding”. The examiner notes that the term is used to mean that something “is” or “corresponds” to something else rather than is a response to something. Additionally, the examiner notes that the term “responding” is used throughout the specification instead of “corresponding” or equivalent. For the purposes of examination, the examiner interprets the term “responding” as “corresponding”.
Claim 18 recites “the alkyl group” without describing which alkyl group of which R group to which “the alkyl group” refers. The examiner notes that the phrase “as a Q group” in the claim and the specification description of the Q group (pg 9, lines 12-15) indicate that “the alkyl group” refers to R2 where R2 is formula II where Q in formula III is an alkyl group optionally substituted with a functional group”. For the purposes of examination, the examiner interprets “the alkyl group” as the alkyl group of Q. Furthermore, the examiner interprets the claim as “The ligand according to claim 16, wherein R2 is formula III where Q group is a linear C5-C20 alkyl group optionally substituted with a functional group.”
Claim 19 recites “the functional group” but there are multiple difference features of the previous claims reciting functional groups, especially in claim 16. The examiner notes that the number of possible groups described in claim 19 as functional groups fitting the various functional groups described before. For the purpose of examination, the examiner interprets “the functional group” to describe any functional group recited in claim 16.
Claim 22 recites “Q represents an alkyl group optionally substituted with a functional group or a polyethylene glycol group”. The examiner notes that this refers to Q from claim 16. Therefore, for the purposes of examination, the examiner interprets the “or” to mean that Q represents either an alkyl group or a polyethylene glycol group.
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.
Claim 18 recites the limitation "the alkyl group" in line 1. There is insufficient antecedent basis for this limitation in the claim.
Claim 19 recites the limitation "the functional group" in line1. There is insufficient antecedent basis for this limitation in the claim.
Claims 16, 20, and 22-23 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being incomplete for omitting essential structural cooperative relationships of elements, such omission amounting to a gap between the necessary structural connections. See MPEP § 2172.01. The omitted structural cooperative relationships are: bond connectivity of groups. As to claim 16, formula (III) methyl group near T, NHR14 in line 15, OH in line 19, CH2OH in line 20, CO2H in line 20, CONHR15 in line 21, OH in line 30, OR16 in line 30, CO2H in line 30, CONHR17 in line 31, CO2H in line 35, and CO2H in line 40 does not explicitly indicate point of connection. As to claim 20, NHR14 in line 1 does not explicitly indicate point of connection. As to claim 22, OH in line 8 does not explicitly indicate point of connection. As to claim 23, CH2OH in line 2 and CO-2H in line 2 do not explicitly indicate point of connection.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
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 CFR 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.
Claim(s) 16-19, 21-29, and 31 is/are rejected under 35 U.S.C. 103 as being unpatentable over Roux, A.; et al. (Roux, A.; et al. Bifunctional bispidine derivatives for copper-64 labelling and positron emission tomography, Org. Biomol. Chem., 2017, 15, 1475, as cited in the IDS filed on 06/27/2024) and Gillet, R.; et al. (Gillet, R.; et al. A Bispidol Chelator with a Phosphonate Pendant Arm: Synthesis, Cu(II) Complexation, and 64Cu Labeling, Inorg. Chem. 2017, 56, 11738-11752) and Perkins, C. M. (WO 00/60045).
Roux, A.; et al. (hereafter referred to as Roux) is drawn to bifunctional bispidine derivatives and substituting pendent arms to achieve fast labelling with copper-64 for positron emission tomography (title; abstract). Roux teaches that bispidine structures are versatile and can easily be reacted to form various derivatives (abstract, lines 6-10). Roux states that bifunctional chelators are good for chelation due to the fast and strong complexation of copper under physiological conditions as well as holding a targeting moiety (pg 1475, col 1, lines 11-15; pg 1475, col 2, line 1) and that bispidine bifunctional chelators are better than DOTA and DOTA-like bifunctional chelators due to the problem of transchelation leading to accumulation of copper-64 in the liver and kidney (pg 1475, col 2, lines 16-20) has led to a design incentive to prompt further research in other types of macrocylic structures such as bispidine (pg 1475, col 2, lines 20-25). Roux states that a variety of derivatives have been designed on bispidine (pg 1476, col 1, para 1, lines 4-10; pg 1477, col 2, para 1, lines 1-3). Roux teaches a variety of bispidine derivatives (p g1476, Fig 1, structures L1-L4) and synthesis route (pg 1476, Scheme 1; pg 1477, Scheme 2; pg 1478, Scheme 3).
As to claim 16, Roux teaches a bispidine-based metal chelating ligand according to formula (I) where R1 is a hydrogen atom (pg 1476, Scheme 1, structure L2); where R2 is a hydrogen atom or a group corresponding to formula (II) where n is 4 (pg 1476, Scheme 1, structure L2), or where R2 is formula III where T is C4 alkylene, A is NH, X is an oxygen atom, and Q is an alkyl group with a terminally substituted functional group (pg 1476, Scheme 1, structure L4); where R3 and R4 are identically CO2H groups (pg 1476, Scheme 1, structure L2); where R5 is an alkyl group (pg 1476, Scheme 1, structure L2); and where R6, R7, R8, R9, R10, R11, R12, and R13 are hydrogen atoms (pg 1476, Scheme 1, structure L2). Roux teaches the proviso when R5 is an alkyl, and R1 and R2 are not both hydrogen atoms (pg 1476, Scheme 1, compound L2).
Roux does not teach the proviso that when R2 is formula (II) and R5 is alkyl, then R3 and R4 are not CO2H groups.
Roux does not teach the proviso that when R2 is formula (III), where T is a C1-C17 alkylene, A is -NH-, X is an oxygen atom, and Q is a C1-C5 alkyl group substituted with a functional group, then R3 and R4 are different from CO2H groups.
Gillet, R.; et al. (hereafter referred to as Gillet) is drawn to a bispidol chelator with a phosphonate pendant arm and a few other derivatives of bispidine to demonstrate improved thermodynamic stability of the phosphonic acid substitution (title; abstract). Gillet teaches that modification of the pendant arms can be used to tune the ligand denticity as well as electronic, thermodynamic, and kinetic parameters such as ligand field, metal selectivity, stability, and redox potentials giving them application in nuclear medicine and diagnosis (pg 11738, col 1, para 1, lines 5-12; pg 11738, Chart 1). Gillet discusses a variety of chelators (pg 11738, Chart 1; pg 11739, Chart 2) and their properties (pg 11739, Table 1) and the synthesis scheme for the phosphonate bispidine (pg 11740, Scheme 1).
Regarding the proviso when R2 is formula II and R5 is alkyl, then R3 and R4 are not CO2H groups, Gillet teaches a structure where R3 and R4 are not both CO2H groups (pg 11738, Chart 1, structure L1).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date to modify the compound of Roux to include R3 and R4 groups that are not both CO2H groups as taught by Gillet because these claim elements were known in the art and one of skill in the art could have combined these elements by known methods with no change in their respective functions, and the combination would have yielded the predictable outcome of a bispidine group with either R3 or R4 being something other than CO2H.
A person of ordinary skill in the art would have had a reasonable expectation of success in combining the substituents of Gillet with the substituents of Roux because the prior art of Roux and Gillet both teach bifunctional bispidine derivatives for copper-64 labelling. The prior art shows the structural similarities of a variety of bispidine containing similar pyridines, N-alkyl, and N-acetic acid, and a bridging carbon hydroxy substituent. Moreover, variants of Gillet show R3 or R4 can be a carboxylic acid or methanol substituent (pg11738, Chart 1, structures L1 or L2). The skilled artisan would have been motivated to have a structure where R3 and R4 are not carboxylic acids because the methanol is the reduced version of the acid and in a synthetic step, a route of synthesis could involve the reducing agent to yield a bridging alcohol as well as reduced R3 and R4 substituents.
Gillet does not explicitly teach both R3 and R4 are not carboxylic acids.
Perkins, C. M. (hereafter referred to as Perkins, WO 00/60045) is drawn to a bispidine and metal complex for bleaching (title; abstract). Perkins teaches a structure with two pyridine substituents, N-alkyl substituents, bridging carbon carboxylic acid, ketone, and hydroxyalkyl substituents (abstract, Formula (I); pg 2, lines 22-35; pg 3, lines 1-4) and can chelate manganese (pg 3, lines 27-33) and is particularly interested in formulas i) and ii) (pg 44, claim 3). Perkins teaches a composition comprising these compounds (pg 2, lines 4-21; pg 43, claims 1-3), and to bleaching and laundry detergent compositions (claims 4-10).
Regarding both R3 and R4 are not carboxylic acids, Perkins teaches a bispidine-metal complex where both R3 and R4 groups are not CO2H groups (claim 8, formula ii).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date to modify the compound of Roux and Gillet to include the feature where both R3 and R4 are not carboxylic acids as taught by Perkins because there was some teaching, suggestion, or motivation, either in the references themselves or in the knowledge generally available to one of ordinary skill in the art, to modify the reference or to combine reference teachings, and the combination would have yielded the predictable outcome of both R3 and R4 not being carboxylic acid groups.
A person of ordinary skill in the art would have had a reasonable expectation of success in using a chelator where both R3 and R4 are not carboxylic acids because the prior art of Gillet suggests a chelator for the same purposes as Roux with either R3 or R4 as not a carboxylic acid, and the prior art of Perkins teaches a chelator where both R3 and R4 are not carboxylic acids. Additionally, the prior art of Perkins has a bispidine chelators that share structural similarities to the bispidine chelators of Roux and Gillet. The skilled artisan would have been motivated to make the modification because when R3 and R4 are not carboxylic acids, there is less steric hindrance in the chelating space which could enable larger groups to attach to the instant application’s R1 or R2 positions.
Regarding when R2 is formula (III), where T is a C1-C17 alkylene, A is -NH-, X is an oxygen atom, and Q is a C1-C5 alkyl group substituted with a functional group, then R3 and R4 are different from CO2H groups, Gillet teaches a structure where R3 and R4 are not both CO2H groups (pg 11738, Chart 1, structure L1).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date to modify the compound of Roux to include R3 and R4 groups that are not both -CO2H groups as taught by Gillet because these claim elements were known in the art and one of skill in the art could have combined these elements by known methods with no change in their respective functions, and the combination would have yielded the predictable outcome of a bispidine group with either R3 or R4 being something other than -CO2H.
A person of ordinary skill in the art would have had a reasonable expectation of success in combining the substituents of Gillet with the substituents of Roux because the prior art of Roux and Gillet both teach bifunctional bispidine derivatives for copper-64 labelling. The prior art shows the structural similarities of a variety of bispidine containing similar pyridines, N-alkyl, and N-acetic acid, and a bridging carbon hydroxy substituent. Moreover, variants of Gillet show R3 or R4 can be a carboxylic acid or methanol substituent (pg11738, Chart 1, structures L1 or L2). The skilled artisan would have been motivated to have a structure where R3 and R4 are not carboxylic acids because the methanol is the reduced version of the acid and in a synthetic step, a route of synthesis could involve the reducing agent to yield a bridging alcohol as well as reduced R3 and R4 substituents.
Gillet does not explicitly teach both R3 and R4 are not carboxylic acids.
Regarding both R3 and R4 are not carboxylic acids, Perkins teaches that a bispidine-metal complex where both R3 and R4 groups that are both not CO2H groups (claim 8, formula ii).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date to modify the compound of Roux and Gillet to include the feature where both R3 and R4 are not carboxylic acids as taught by Perkins because there was some teaching, suggestion, or motivation, either in the references themselves or in the knowledge generally available to one of ordinary skill in the art, to modify the reference or to combine reference teachings, and the combination would have yielded the predictable outcome of both R3 and R4 not being carboxylic acid groups.
A person of ordinary skill in the art would have had a reasonable expectation of success in using a chelator where both R3 and R4 are not carboxylic acids because the prior art of Gillet suggests a chelator for the same purposes as Roux with either R3 or R4 as not a carboxylic acid, and the prior art of Perkins teaches a chelator where both R3 and R4 are not carboxylic acids. Additionally, the prior art of Perkins has a bispidine chelators that share structural similarities to the bispidine chelators of Roux and Gillet. The skilled artisan would have been motivated to make the modification because when R3 and R4 are not carboxylic acids, there is less steric hindrance in the chelating space which could enable larger groups to attach to the instant application’s R1 or R2 positions.
As to claim 17, Roux teaches T is C4 (pg 1477, Scheme 2, L3). C4 is a specific example in the prior art which is within the claimed range of C1-C17. In such cases, the range is anticipated but since claim 17 carries the limitations of claim 16, C1-C17 is rendered prima facie obvious. See MPEP 2131.03.
As to claim 18, Roux teaches Q is an alkyl group of C2 (pg 1477, Scheme 2, structure L4) and another alkyl group of C5 before an attachment to a functional group (pg 1477, Scheme 2, structure L3). A range can be disclosed in multiple prior art references instead of in a single prior art reference depending on the specific facts of the case. See MPEP 2144.05(I). In this case, C2 and C5 form a range, even though they are on different structure references within Roux. The prior art range of C2 to C5 overlaps with the claimed range of C5-C20. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. See MPEP 2044.05(I).
As to claim 19, Roux teaches a functional group is amide (pg 1477, Scheme 2, structure L4).
As to claim 21, Roux teaches R2 is formula (II) (pg 1476, Scheme 1, structure L2) or formula (III) (pg 1477, Scheme 2, structure L4).
As to claim 22, Roux teaches that A is -NH-, X is an oxygen atom, and Q is an alkyl group (pg 1476, Scheme 1, structure L-2).
As to claim 23, Roux teaches that R3 and R4 are identical as CO2H (pg 1476, Scheme 1, structure L2).
As to claim 24, Roux teaches that R3 and R4 are identical (pg 1476, Scheme 1, structure L2).
As to claim 25, Roux teaches R5 is a methyl (pg 1476, Scheme 1, structure L2).
As to claim 26, Roux teaches R5 is a linear alkyl group, methyl (pg 1476, Scheme 1, structure L2).
As to claim 27, Roux teaches R6-R13 are hydrogen atoms (pg 1476, Scheme 1, structure L2).
As to claim 28, Roux teaches a structure similar to formula I-c. Roux teaches bispidine-based metal chelating ligand according to formula (I) where R1 is a hydrogen atom (pg 1476, Scheme 1, structure L2); where R2 is a group corresponding to formula (II) where n is 4 (pg 1476, Scheme 1, structure L2; where R5 is an alkyl group (pg 1476, Scheme 1, structure L2); and where R6, R7, R8, R9, R10, R11, R12, and R13 are hydrogen atoms (pg 1476, Scheme 1, structure L2).
Roux does not teach where R3 and R4 are not CO2H groups.
Gillet teaches a structure where R3 and R4 are not both CO2H groups (pg 11738, Chart 1, structure L1).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date to modify the compound of Roux to include R3 and R4 groups that are not both CO2H groups as taught by Gillet because these claim elements were known in the art and one of skill in the art could have combined these elements by known methods with no change in their respective functions, and the combination would have yielded the predictable outcome of a bispidine group with either R3 or R4 being something other than CO2H.
A person of ordinary skill in the art would have had a reasonable expectation of success in combining the substituents of Gillet with the substituents of Roux because the prior art of Roux and Gillet both teach bifunctional bispidine derivatives for copper-64 labelling. The prior art shows the structural similarities of a variety of bispidine containing similar pyridines, N-alkyl, and N-acetic acid, and a bridging carbon hydroxy substituent. Moreover, variants of Gillet show R3 or R4 can be a carboxylic acid or methanol substituent (pg 11738, Chart 1, structures L1 or L2). The skilled artisan would have been motivated to have a structure where R3 and R4 are not carboxylic acids because the methanol is the reduced version of the acid and in a synthetic step, a route of synthesis could involve the reducing agent to yield a bridging alcohol as well as reduced R3 and R4 substituents.
Gillet does not explicitly teach both R3 and R4 are not carboxylic acids.
Regarding both R3 and R4 are not carboxylic acids, Perkins teaches that a bispidine-metal complex where both R3 and R4 groups that are both not CO2H groups (claim 8, formula ii).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date to modify the compound of Roux and Gillet to include the feature where both R3 and R4 are not carboxylic acids as taught by Perkins because there was some teaching, suggestion, or motivation, either in the references themselves or in the knowledge generally available to one of ordinary skill in the art, to modify the reference or to combine reference teachings, and the combination would have yielded the predictable outcome of both R3 and R4 not being carboxylic acid groups.
A person of ordinary skill in the art would have had a reasonable expectation of success in using a chelator where both R3 and R4 are not carboxylic acids because the prior art of Gillet suggests a chelator for the same purposes as Roux with either R3 or R4 as not a carboxylic acid, and the prior art of Perkins teaches a chelator where both R3 and R4 are not carboxylic acids. Additionally, the prior art of Perkins has a bispidine chelators that share structural similarities to the bispidine chelators of Roux and Gillet. The skilled artisan would have been motivated to make the modification because when R3 and R4 are not carboxylic acids, there is less steric hindrance in the chelating space which could enable larger groups to attach to the instant application’s R1 or R2 positions.
Therefore, the combined teachings of Roux, Gillet and Perkins render formula I-c obvious.
As to claim 29, Roux teaches a complex of copper with the bispidine-based chelating ligand (pg 11742, col 2, para 3, lines 7-8).
As to claim 31, Roux teaches positron emission tomography agent comprising a bispidine-based metal chelating ligand with copper (title; abstract; pg 1479, col 2, para 2, lines 1-4).
Claim(s) 20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Roux and Gillet and Perkins as applied to claims 16-19, 21-29, and 31 above, and further in view of Adams, C. J..; et al. (Adams, C. J.; Krueger, R.; Meade, T. J. A Multimodal Ca(II) Responsive Near IR-MR Contrast Agent Exhibiting High Cellular Uptake, ACS Chem. Biol. 2020, 15, 334-341). The teachings of Roux and Gillet and Perkins as applied in the previous rejection are incorporated in this rejection.
As to claim 20, Roux teaches R2 is formula III where T is C4 alkylene, where A is NH, where X is an oxygen atom, and where Q is an alkyl group with a terminally substituted functional group (pg 1476, Scheme 1, structure L4
The combined teachings of Roux, Gillet, and Perkins do not teach Q is a -NHR14 group where R14 is a C5-C20 optionally substituted with a functional group.
Adams, C. J.; et al. (hereafter referred to as Adams) is drawn to a multimodal contrast agent with chelating groups and a targeting group (title; abstract). Adams teaches some structures of contrast agents using DOTA-like chelators with two acetic acid N-substituents, a lysine-like N-substituent, and an alkyl N-substituent where the lysine N-substituent is used for bioconjugation to a NIR dye (pg 335, Figure 1). Adams teaches the synthesis of the contrast agent (pg 336, Scheme 1), magnetic field strength (pg 336, Table 1), and magnetic resonance imaging (abstract; pg 338, Figure 4; pg 339, col 1, para 2, lines 19).
Adams teaches Q is a -NHR14 group where R14 is a C6 aryl that is attached to a functional group (pg 335, Figure 1, structure 1, where R is structure 5).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date to modify the compound of Roux, Gillet, and Perkins to include the Q group as taught by Adams because these claim elements were known in the art and one of skill in the art could have combined these elements by known methods with no change in their respective functions, and the combination would have yielded the predictable outcome of a chelator with a lysine-like N-substituent with a linkage to a Q group where that Q group is an aryl with a functional group.
A person of ordinary skill in the art would have had a reasonable expectation of success in combining the Q group of formula II shown in Adams with the formula II group of Roux, Gillet, and Perkins because the prior art of Roux disclosed chelators for imaging that can chelate metals and contains a variety of N-substituents including a lysine-like N-substituent which is known to be able to conjugate to other features (Roux, pg 1477, Scheme 2). Additionally, the prior art of Roux suggested that other chelators such as DOTA and NOTA are commonly studied by people in the field and have properties that enable chelation because of the overlap in the substituent groups. Additional prior art of Adams is drawn to DOTA-like chelators for imaging with three similar N-substituents and the overlap of the structure of the lysine-like N-substituent between them involves known reactions and materials.
The skilled artisan would have been motivated to modify R2 group with the Q group of Adams because of the ability to attach additional labels, tags, and targeting groups onto the terminal amine group of the lysine-type N-substituent.
Claim(s) 30 is/are rejected under 35 U.S.C. 103 as being unpatentable over Roux and Gillet and Perkins as applied to claims 16-19, 21-29, and 31 above, and further in view of Ndiaye, D.; et al. (Ndiaye, D.; et al. Unprecedented Kinetic Inertness for a Mn2+-Bispidine Chelate: A Novel Structural Entry for Mn2+-Based Imaging Agents, Angew. Chem. Int. Ed. 2020, 59, 11958-11963, as cited in the IDS filed on 06/27/2024). The teachings of Roux and Gillet and Perkins as applied in the previous rejection are incorporated in this rejection.
As to claim 30, Roux teaches a bispidine-based metal chelating ligand which can complex to copper and can be used for imaging (title; abstract; pg 1482, col 1, para 3, lines 7-11).
The combined teachings of Roux, Gillet, and Perkins do not explicitly teach that it is a magnetic resonance imaging contrast agent.
Ndiaye, D.; et al. (hereafter referred to as Ndiaye) is drawn to a manganese bispidine chelate for imaging with excellent kinetic inertness showing no dissociation for 140 days in the presence of a competing meta (title; abstract). Ndiaye teaches a need for manganese and other paramagnetic metals over gadolinium due to the brain and bone accumulation associated with gadolinium (pg 11958, col 1, para 1, lines 1-11; pg 11958, col 2, para 2, lines 1-2). Ndiaye teaches that the bispidine is a versatile and stable platform where various pendant arms can be attached in different positions to tune the coordination properties for metal ions (pg 11959, col 1, para 2, lines 4-19). Ndiaye teaches that a methylene carboxylate is useful for MRI and for potential bioconjugation (pg 11959, col 1, para 3, lines 1-14). Ndiaye teaches multiple potential chelators (pg 11959, Scheme 1; pg 11959, Scheme 2) and the stability of the manganese bispidine compared to other ligands (pg 11959, Table 1) and biodistribution (pg 11962, Figures 5-7).
Regarding the MRI contrast agent, Ndaiye teaches contrast agents for MRI (abstract; pg 11959, col 2, para 2, lines 5-7).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date to modify the composition of the combined teachings of Roux, Gillet, and Perkins to include a metal that works well for MRI as taught by Ndaiye because these claim elements were known in the art and one of skill in the art could have combined these elements by known methods with no change in their respective functions, and the combination would have yielded the predictable outcome of a bispidine chelator with manganese for MRI.
A person of ordinary skill in the art would have had a reasonable expectation of success in using bispidine chelators for MRI because the prior art of Roux, Gillet, and Perkins disclosed the same chelator for chelating metals. Additional prior art of Ndaiye teaches that the chelator combined with manganese works well as an MRI contrast agent. The skilled artisan would have been motivated to use the bispidine chelator for MRI because metal-based chelators used as MRI can help diagnose cancers and aid in more imaging capabilities of the chelator-metal complex.
Conclusion
No claims allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Evan M Lewoczko whose telephone number is (571)272-9830. The examiner can normally be reached Monday-Friday 9-5PM.
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/EVAN M LEWOCZKO/Examiner, Art Unit 1612
/SAHANA S KAUP/Supervisory Primary Examiner, Art Unit 1612
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