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 .
An amendment and RCE filed 2/20/2026 are acknowledged. Claims 1-4 and 6-15 are pending. Claim 5 is cancelled. Claims 1-4 and 6-15 are considered on the merits below.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 2/20/2026 has been entered.
Response to Amendment
Applicant's amendments, filed 2/20/2026, with respect to the objections to the specification and claims have been fully satisfied and withdrawn.
In response to the applicant's amendments, the grounds of rejection for claims 1-4 and 6-15 are new compared to the previous action.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-4 and 6-15 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more.
Step 2A, Prong 1: identify the abstract ideas. In claim 1, step (e) is “quantifying” the signal which is either a mental process or math. The MPEP holds that both evaluations and mathematical calculations are abstract ideas (MPE 2106.04(a)).
Step 2A, Prong 2: has the abstract idea been integrated into a particular practical application? In claim 1, steps (a)-(d) are just data gathering steps which are insignificant pre-solution activity, and not a particular practical application. Data gathering and/or generically applying an abstract idea have been deemed to not be integrated into a practical application, there must be a meaningful limit to the judicial exception which is claimed (MPEP 2106(f) and (g)).
Step 2B: does the claim recite any elements which are significantly more than the abstract idea? In claim 1, the data gathering steps using the luminescent agent are well-known, routine, and conventional (see references below for support). Thus the claim does not recite “significantly more”.
Dependent claims only further refine the abstract idea.
Claim Rejections - 35 USC § 112
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 1-4 and 6-15 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.
Regarding claim 1, the limitation “Gd+” (lines 9 and 11), is indefinite because it is unclear if the signal detected is from Gd+ or Gd3+ (as described prior in the claim and specification). For examination purposes the examiner interprets that the limitation reads “Gd3+”.
Regarding claims 7 and 8, the limitation in claim 7 “the range of wavelength is from about 590 nm to 640 nm” is indefinite because it is unclear if this means the excitation or the emission wavelength. The claims take antecedent basis from claim 1 which implies the excitation wavelength, however the specification and the drawings indicate that this range is for the emissions wavelengths. For examination purposes the examiner interprets that these are the emission wavelengths.
Regarding claim 8, the limitation “the range of wavelength is about 620 nm” is indefinite because a range is not provided. For examination purposes the examiner interprets that the limitation reads wherein “the wavelength is about 620 nm”.
Regarding claim 13, the limitation “-CH2-ȹ” is indefinite because “ȹ” is not defined. For examination purposes the examiner interprets that it is any substituent.
Dependent claims follow the same reasoning.
Response to Arguments
Applicant’s arguments with respect to claims 1-4 and 6-15 have been considered but are moot because the arguments do not apply to the current rejection.
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) 1-4 and 6-14 is/are rejected under 35 U.S.C. 103 as being unpatentable over Rees et al. (Scientific Reports (2018) 8:4419, provided on the IDS on 2/13/2023) in view Abergel et al. (Inorg. Chem. 2009, 48, 10868–10870, plus supporting information).
Regarding claim 1, Rees describes a method to detect and/or quantify a gadolinium-based contrast agents (GBCA) in a sample (abstract), the method comprising:
(a) providing a sample (abstract “brain, bones, and other organs of patients”);
(b) contacting the sample with a luminescent agent so that luminescent agent chelates a Gd3+ cation of the GBCA (abstract “agent 3,4,3-LI(1,2-HOPO) (luminescent agent) demonstrates superior efficacy at chelating and removing Gd”);
However Rees is silent to (c) exposing the luminescent agent to one or more, or a range of, wavelengths of light to cause the luminescent agent to produce a luminescence emission; (d) detecting a signal of only Gd+ complex of luminescence emissions; and (e) quantifying the signal of Gd+ complex luminescence emissions.
Abergel describes (c) exposing the luminescent agent to one or more, or a range of, wavelengths of light to cause the luminescent agent to produce a luminescence emission (page 10869 “the phosphorescence of the ligand can be observed by luminescence measurements” and Figure S1); (d) detecting a signal of only Gd+ complex of luminescence emissions (Figure S1); and (e) quantifying the signal of Gd+ complex luminescence emissions (Figure S1). Furthermore Abergel suggests this measurement is important to understanding the “coordination chemistry and photophysical properties of the Gd(III) and Eu(III) complexes” (page 10868). Additionally, Rees suggest motivation obtain fluorescent measurements of Gd compounds (page 7 “Due to its high denticity and steric bulk, we anticipate Gd-HOPO to be an ineffective MRI contrast agent, since all coordination sites of Gd3+ should be occupied and no water molecules are expected within the first coordination sphere, consistent with findings from time-resolved fluorescence measurements on the corresponding Eu3+ complex”), as this would allow for a more comprehensive picture of the chemistry of these compounds.
Therefore it would have been obvious for one skilled in the art at the time of filing to incorporate the steps of exposing, detecting, and quantifying of Gd3+ compounds into the method of Rees as suggested by Abergel and Rees because increases the understanding of the coordination and allows for a more comprehensive picture of the chemistry of these compounds
Regarding claim 2, the combination described above describes the method of claim 1, wherein the providing step (a) comprises obtaining the sample from a subject (Rees: page 2 “subject animals”).
Regarding claim 3, the combination described above describes the method of claim 2, wherein the sample obtained from the subject is not further treated, prepared, or digested prior to the contacting step (b) (Rees: page 8 “in vivo studies”).
Regarding claim 4, the combination described above describes the method of claim 1, wherein the contacting step (b) comprises incubating the sample and the luminescent agent together (Rees: figure 2 “Total murine body content and distribution of 153Gd four days following contamination via intravenous injection into a warmed lateral tail vein, reported as % RD. Treatments were administered at a dose of 100 μmol/kg via ip injection at times varying from 24 h pre- to 48 h post-Gd injection.”).
Regarding claim 6, the combination described above describes The method of claim 1, wherein the luminescent agent in contacting step (b) is chelated to Eu3+ (Rees: page 5 “the decorporation of other f-elements such as… 152Eu3+, HOPO is more effective than DTPA at reducing the overall skeletal content of the heavy metal, even when administered up to 48 h post-contamination”)
Regarding claim 7, the combination described above describes the method of claim 1, wherein the range of wavelength is from about 590 nm to 640 nm (Abergel: page 10869 “emission band from 400 to 570nm” and figure S1 shows wavelength is from about 590 nm to 640 nm).
Regarding claim 8, the combination described above describes the method of claim 7, wherein the range of wavelength is about 620 nm (Abergel: page 10869 “emission band from 400 to 570nm” and figure S1 shows wavelength is about 620 nm).
Regarding claim 9, the combination described above describes the method of claim 1, wherein the gadolinium-based contrast agent (GBCA) is selected from the group of gadopentetate, gadobenate, and gadodiamide (Rees: abstract “GBCA Gadopentetate (Magnevist)”).
Regarding claim 10, the combination described above describes the method of claim 1, wherein the sample is a bodily fluid or a fluid obtained from a body (Rees: page 4 “53Gd recovered from the excreta of all study groups, as well as the relative amounts found in the urine and feces”).
Regarding claim 11, the combination described above describes The method of claim 10, wherein the sample is blood, serum, or urine (Rees: page 4 “53Gd recovered from the excreta of all study groups, as well as the relative amounts found in the urine and feces”).
Regarding claim 12, the combination described above describes the method of claim 1, wherein the luminescent agent is a 1,2- HOPO chelating agent or 3,2-HOPO chelating agent (Rees: page 7 “1,2-HOPO”).
Regarding claims 13, the combination described above describes The method of claim 12, wherein the luminescent agent is a 1,2-HOPO chelating agent defined by the structure:
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170
676
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where R1 and R2 are selected from the group consisting of H, -CH3, -CH2CH3 and -CH2-ȹ , and X is either hydrogen, an alkali metal ion, or quaternary ammonium ion (Rees: figure 1
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384
326
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and page 7 “3,4,3-LI(1,2-HOPO)”).
Regarding claim 14, the combination described above describes the method of claim 13, wherein the 1,2-HOPO chelating agent comprises a following
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510
656
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;
wherein l, m and n are integers between one and twenty (Rees: figure 1
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384
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and page 7 “3,4,3-LI(1,2-HOPO)”).
Claim(s) 15 is/are rejected under 35 U.S.C. 103 as being unpatentable over Rees et al. (Scientific Reports (2018) 8:4419, provided on the IDS on 2/13/2023) in view Abergel et al. (Inorg. Chem. 2009, 48, 10868–10870, plus supporting information) in further view of Butlin et al. (US 2012/0214253 A1).
Regarding claim 15, the combination described above describes he method of claim 12, however is silent to wherein the luminescent agent is a 3,2- HOPO chelating agent defined by the structure:
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222
420
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wherein Ri is a member selected from the group consisting of hydrogen, C1-4 aliphatic hydrocarbon groups, and C1-4 aliphatic hydrocarbon groups substituted by a single halide, hydroxy, carboxy, or aryl group; Z is a member selected from the group consisting of O, NH, N-alkyl, and N- aryl; a is 2-4; and b is 2-4.
Butlin describes both "chelating moieties 1,2-HOPO or 3,2-HOPO" for chelating Gd (figure 8). This suggests that these are known art equivalents for the same purpose for chelating gadolinium, providing motivation to substitute one for the other.
Therefore it would have been obvious to one skilled in the art at the time the invention was filed, to modify the 1,2-HOPO of the combination as suggested by Butlin because they are known art equivalents used for the same purpose if chelating gadolinium.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to EMILY R BERKELEY whose telephone number is (571)272-9831. The examiner can normally be reached M-Th 9-6.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lyle Alexander can be reached at (571) 272-1254. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/EMILY R. BERKELEY/
Examiner
Art Unit 1796
/LYLE ALEXANDER/Supervisory Patent Examiner, Art Unit 1797