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 .
Applicants' arguments, filed 04/02/2026, 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 Rejections and/or objections not reiterated from previous office actions are hereby withdrawn.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 Rejections - 35 USC § 103--Previous
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.
Claim(s) 1-11 remain rejected under 35 U.S.C. 103 as being unpatentable over Andrews et al., (WO 2000/12083, cited in IDS) in view of Gennadievich et al., (WO 2020/031136).
Andrews et al. teaches hydroxamate metalloprotease inhibitors having the following structure, as per the instant claim 1, shown below:
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192
479
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(p. 3, lines 23-26).
Andrews et al. teaches a specific embodiment, as per claim 11:
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84
817
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(p. 80, lines 16-17, Example 1).
The prior art teaches “where R1 is methyl, ethyl, isopropyl 4-methyl-1-pentyl . . .” (p. 113, lines 11), as per claims 2-3; “R2 is . . . 3-phenyl-1-propyl . . . “(p. 113, line 18), as per claim 4; “R4 is tert-butyl” (p. 114, lines 13), as per claim 5; “R6 is methyl” (p. 115, line 8), as per claims 6-7.
Andrews et al. teaches, “Compounds which inhibit activities of one or more of the matrix metalloproteases are recognized as having therapeutic benefit in one or more pathologies where MMP activity is upregulated, such as: . . . “diseases of cancer and malignancy, including but not limited to cancers of the oral cavity and pharynx (lip, tongue, mouth, pharynx), esophagus, stomach, small intestine, large intestine, rectum, liver . . . lung, bone, connective tissue . . . colon, breast, cervix uteri . . .prostate “ (p. 2, lines 19-27 through p. 3, line 4).
Andrews et al. teaches attaching an “affinity reagent” to the formulas “which does not affect its in vitro biological activity, allowing the compound to bind to a target, yet such a group binds strongly to a third component allowing a) characterization of the target as to localization within a cell or other organism component, perhaps by visualization by fluorescence or radiography” (p. 51, lines 11-15).
Andrews et al. does not teach wherein the N-hydroxamide is radiolabled with a radionucleotide.
Gennadievich et al., “Integration of targeted therapy and diagnostics have created a new field of treatment called theranostics. The main task of the discipline is the potential ability to track the progress of target delivery of drugs or other pharmaceutically acceptable derivatives using molecular imaging in the study subjects” (p. 1, 2nd paragraph).
Gennadievich et al. further teaches “making SANPs-theranostics with adjuvant effect turned to therapy and diagnostic of prostate cancer and possible ways of usage” (p. 2, last paragraph). “In the application to therapy and diagnosis of prostate cancer the first ‘theranostic’-alike delivery methods used the well-known readioactive labels to detect the accumulation of drug” (p. 1, last paragraph). For example, Gennadievich et al. teaches use of iodine-123 as radionuclide theranostic in its method of treating prostate cancer (see p. 6, last paragraph).
It would have been obvious to a person having ordinary skill in the art at the time of applicant’s filing to use theranostics, of Gennadievich et al., to treat cancers of Andrews et al. since Andrews teaches cancer treatment as well as localization of its compounds within a cell or other organism for visualization by radiography. Since Andrews et al. teaches where R2 is “3-(4-chlorophenyl)-1-propyl” (p. 114, line 1), it would have been reasonable for the artisan to take advantage of neophilic halogen exchange and substitute the chloro- atom with iodine-123, thus creating a radiolabeled compound for radiography and treatment via theranostics. Replacing the chlorine with iodine-123 would place the radionuclide in the para-position, as per claim 10.
Technological Background
1) The prior art made of record is considered pertinent to applicant's disclosure Cuthbertson et al., (US 2007/0104644, cited in IDS). Cuthbertson et al. is pertinent for teaching “imaging agents which comprise a specific type of matrix metalloprotease inhibitors (MMPi’s) of the sulphonamide hydroxamate class labelled with an imaging moiety, are useful diagnostic imaging agents for in vivo imaging and diagnosis of the mammalian body” (Abstract).
2) The prior art made of record is considered pertinent to applicant's disclosure Dubost et al, (The Journal of Organic Chemistry). Dubost et al. is pertinent for teaching recent advances in synthetic radioiodination. Dubost et al. teaches, “Electrophilic aromatic substitution is a very popular strategy to perform radioiodination, which can be applied either directly with the compound of interest or using a prefunctionalized precursor” (p. 8302, section. 1.2) Specifically, “Direct SEAr”, is a direct electrophilic aromatic substitution, which “exhibits low regioselectivity” and “can lead to the radioiodinated compound with good RCY and high molar activity” (Id.).
Response to Arguments
i) Applicant argues Gennadievich is non-analogous art insofar as it teaches self-assembled nanoparticles, which, according to applicant, is “fundamentally different technology from the small-molecule hydroxamate MMP inhibitors of Andrews” (p. 4-5).
The Examiner disagrees.
In response to applicant's argument that Gennadievich et al. is nonanalogous art, it has been held that a prior art reference must either be in the field of the inventor’s endeavor or, if not, then be reasonably pertinent to the particular problem with which the inventor was concerned, in order to be relied upon as a basis for rejection of the claimed invention. See In re Oetiker, 977 F.2d 1443, 24 USPQ2d 1443 (Fed. Cir. 1992). In this case, Gennadivech et al. in the field of the inventor’s endeavor and reasonably pertinent to applicants’ problem since deals with theranositc compounds, which is the title of applicant’s invention. It also teaches use of radiolabled iodine, i.e., Iodine-123, which applicant uses to label G1254023X (see Spec. at p. 12).
ii) Applicant argues that Andrews “does not provide motivation to combine with Gennadivech’s nanoparticle theranostics” and “[t]he Examiner has not articulated why a person of ordinary skill would extract the concept of iodine-123 form Gennadievich’s nanoparticle platform and apply it to directly radiolabel the small-molecule hydroxamate compounds of Andrews” (p. 5)
However, it must be remembered, "A person of ordinary skill in the art is also a person of ordinary creativity, not an automaton." KSR International Co. v. Teleflex Inc., 82 USPQ2d at 1397. "[I]n many cases a person of ordinary skill will be able to fit the teachings of multiple patents together like pieces of a puzzle."Id. Office personnel may also take into account "the inferences and creative steps that a person of ordinary skill in the art would employ."Id. at 1396.
In this case, the primary reference, Andrews et al., in addition to teaching the claimed compound structure, also teaches use of “radiography” for characterization of a target as to localization within a cell or other organism component (Andrews p. 51, lines 11-15). In radiography, radiolabeled materials are used to visualize, diagnose, and treat diseases. Since the diseases mentioned in Andrews include prostate cancer, for example, it would have been obvious to have relied on known theranositc approaches, such as iodone-123, taught in Gennadivech et al., to visualize and treat prostate cancer.
iii) Applicant argues that neophilic halogen exchange would not be applicable to the 4-chlorophenyl group of Andrews et al. since it lacks “activated substrates with electron-withdrawing groups ortho or para to the leaving group” (p. 6).
However, neophilic halogen exchange, also termed the Finkelsteing reaction, involves the exchange of one halogen atom for another, which would have been reasonable since the group of Andrews et al. comprises a halogen at the para position. While there is no teaching in the art to suggest this technique, it seemed obvious to perform a halogen exchange reaction to take advantage of the radiography taught in Andrews et al.
Nevertheless, “Arguments presented by the applicant cannot take the place of evidence in the record. In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965) and In re De Blauwe, 736 F.2d 699, 705, 222 USPQ 191, 196 (Fed. Cir. 1984). No evidence has been presented by applicant demonstrating the impossibility of performing a neophilic halogen exchange of the 4-chlorophenyl group of Andrews et al.
Moreover, “when there is a motivation to solve a problem and there are a finite number of identified, predictable solutions, a person of ordinary skill in the art has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense.” KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385, 1390.
Other known techniques for radiolabeling compounds may also be employed, for example, Dubost et al. (above) teaches electrophilic aromatic substitution, which would have also been feasible since the compounds of Andrews et al. include aromatic (i.e. phenyl) groups.
iv) Applicant argues “the Examiner has not explained how a person of ordinary skill in the art would radiolabel GI254023X recited in clam 11 (p. 6-7).
Claim 11 identifies a species of the compound structure of claim 1, which applicant admits is the same as Example 1 of Andrews et al.
Claim 11 is not drawn to a method of radiolabeling GI254023X. It is a product that depends from claim 1. It is already radiolabeled in view of the claim 1, but the claim does not indicate where the radiolabel is placed in the molecule. Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). It would have been obvious to radiolabel GI254023X in view of Andrews et al.
Conclusion
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.
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Any inquiry concerning this communication or earlier communications from the examiner should be directed to WALTER E WEBB whose telephone number is (571)270-3287 and fax number is (571) 270-4287. The examiner can normally be reached from Mon-Fri 7-3:30.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sahana Kaup can be reached (571) 272-6897. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Walter E. Webb
/WALTER E WEBB/ Primary Examiner, Art Unit 1612
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