DETAILED ACTION
Applicants’ arguments, filed April 24, 2026, have been fully considered. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Claim Status
Claims 1 and 2 are pending and under examination.
Drawings
The drawings are objected to for the following reasons.
The images of Fig. 5B and Fig. 6B are not readily interpretable in their current state. Both figures are associated with a scale intended to communicate the intensity of a measured value. However, the examiner is unable to interpret the meaning of the dark colored regions of the figures as this may correspond to either high or low intensities based on the provided scales. A linear intensity gradient is required to interpret these data.
Appropriate correction is required.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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.
Claims 1-2 stand rejected under 35 U.S.C. 103 as being unpatentable over Yan (Yan, X. et. al., Angew. Chem. Int. Ed., 2012) in view of Okamura (Okamura, H. et. al., Circ. Cardiovasc. Imaging., 2014), as evidenced by Bottrill (Bottrill, M., Chem. Soc. Rev., 2006).
Yan teaches a nearly identical molecule to Formula 1, only differing in a DOTA-coordinated europium ion instead of the gadolinium ion of the claimed invention (pg. 3359, Scheme 1). The Yan molecule contains a lanthanide metal coordinated in a DOTA chelating group and the phenylsulfonyl fluoride serine protease activity-based reactive probe moiety. The Yan molecule further teaches combining the aforementioned groups through the same linker moiety as the claimed molecule synthesized by the same azide-alkyne cycloaddition click chemistry.
Yan fails to teach a molecule comprising a coordinated gadolinium ion.
Okamura teaches an MRI contrast agent comprising Gd-DOTA. This molecule, LMI1174 (pg. 694, Fig. 3A), uses gadolinium as the lanthanide for the contrast agent portion of the composition. Like Yan, the lanthanide-DOTA is covalently linked to a targeting moiety. In this way, the structural features of LMI1174 are analogous to those of the claimed Gd-DOTA-click-SF and the composition serves the same purpose as the claimed invention addresses.
As evidenced by Bottrill, both gadolinium and europium are lanthanide metals known to be effectively used in MRI contrast agents (pg. 560, section 2 and pg. 561, section 3.1, respectively). A chemical composition and its properties are inseparable (MPEP §2112.01). Thus, the Yan Eu-DOTA-click-SF composition has the property that it would be capable of use as an MRI contrast agent.
A person of ordinary skill in the art would have recognized that both the Eu-DOTA-click-SF and LMI1174 molecules were capable of serving as contrast agents for imaging. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the serine protease targeting agent of Yan by incorporating the teaching of Okamura and substitute gadolinium into the DOTA group instead of europium because both europium and gadolinium are known to be lanthanide metals used in contrast agents, as evidenced by Bottrill. This would yield the predictable result of a serine protease targeting MRI contrast agent capable of use for imaging vascular disease.
Furthermore, as discussed above, claim 2 is interpreted to require the structure of claim 1. Therefore, the combined teachings of Yan and Okamura, as evidenced by Bottrill, render claims 1 and 2 obvious.
Response to Arguments
First, Applicant asserts that a person having ordinary skill in the art would not have had a reasonable expectation of success in combining the teachings of Yan and Okamura, nor a reason for doing so. Applicant argues that this is because Yan teaches a molecule for molecular mass spectrometry while Okamura teaches a molecule for MRI. Applicant asserts that the cited art fails to provide any reason to alter Yan’s mass spectrometry molecule so as to arrive at the presently claimed invention. It is further asserted that Okamura provides no reasonable expectation that Yan’s molecular mass spectrometry molecule would be successfully used as a magnetic resonance imaging or computed tomography contrast agent.
Second, Applicant asserts that the contrast agent nature of the presently claimed invention is an unexpected result that distinguishes it from the cited art. Applicant argues that this is because Yan does not disclose or suggest that the Eu-DOTA-click-SF molecule may be used as a contrast agent and Okamura fails to provide a disclosure that Yan’s molecule would be successfully used as such.
Third, Applicant asserts that the amended claims reciting that “the contrast agent is configured to be used as a magnetic resonance imaging or computed cosmography contrast agent” require a person having ordinary skill in the art altering Yan’s molecule to have a reasonable expectation that it could be used as a contrast agent as presently claimed.
First, respectfully, this argument is not persuasive. As stated in the rejection, Bottrill discloses that a practitioner of contrast agents would recognize that compounds containing chelated europium or chelated gadolinium are both suitable for use as MRI contrast agents. Since a person having skill in the art would recognize both Yan and Okamura as targeted contrast agents for vascular imaging, there would be a high expectation of success in substituting the europium of Yan with the gadolinium of Okamura. The expectation of success is indeed evidenced by Bottrill describing gadolinium and europium contrast agents as alternatives to each other (pg. 561, Section 3.1, paragraph 1). While applicant argues that the art does not provide a reason for making such a substitution, an express suggestion to substitute one equivalent component for another is not necessary to render such substitution obvious (MPEP § 2144.06(II)).
Second, respectfully, this argument is not persuasive. As stated in MPEP § 716, Applicant’s assertion of unexpected results requires objective evidence, i.e. data. Furthermore, per, MPEP § 716.01(c), to be of probative value, any objective evidence should be supported by actual proof. In the instant case, applicant has not provided tests comparing the claimed invention to the closest prior art. Arguments by applicant cannot take the place of evidence. Furthermore, the burden is on the applicant to establish results are unexpected and significant (MPEP § 716.02(b)). In the instant case, applicant has not provided evidence that the compound of Yan does not possess contrast agent properties. Additionally, en arguendo, as stated in the rejection, Bottrill discloses that a practitioner of contrast agents would recognize that compounds containing chelated europium or chelated gadolinium are both suitable for use as MRI contrast agents. While Yan teaches using the Eu-DOTA-click-SF compound for use in molecular mass spectrometry, properties (e.g., suitability as a contrast agent) are inseparable from a chemical composition (MPEP § 2112.01). Thus, a person having ordinary skill in the art of contrast agents would recognize that the compound taught by Yan would be capable of use as an MRI contrast agent. Therefore, the modification of the molecule of Yan producing a molecule capable for use as a contrast agent is not an unexpected result over the prior art.
Third, respectfully, this argument is not persuasive. As described above, while Yan does not explicitly teach the Eu-DOTA-click-SF compound to have contrast agent properties, Bottrill provides evidence that this molecule would be capable of this function and a person having ordinary skill in the art would recognize the molecule of Yan as being suitable for use as a contrast agent for MRI or CT. Furthermore, the amended language of claim 1 is considered by the examiner to be intended use language. A recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. In this case, the amended language does not impart any additional structural requirement beyond what was already required in the claim.
Therefore, the rejection of claims 1 and 2 as obvious over Yan and Okamura as evidenced by Bottrill is maintained.
Conclusion
All claims are rejected.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Eric P Mosher whose telephone number is (571)272-3258. The examiner can normally be reached Monday-Friday 9am-5pm.
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/E.P.M./Examiner, Art Unit 1612
/SAHANA S KAUP/Supervisory Primary Examiner, Art Unit 1612
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