DETAILED ACTION
This Office action details a non-final action on the merits for the above referenced application No. Claims 60-64 are pending in this application.
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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 31 Oct. 2025 has been entered.
Status of Claims
Claims 1-59 are cancelled. Claims 60-61 are amended.
Response to Amendment
The amendments filed on 31 Oct. 2025 have been entered.
The declaration under 37 CFR 1.132 filed 31 Oct. 2025 is insufficient to overcome the rejection of claims as set forth in the last Office action because of the reasons set forth below.
Dr. Hammoud declares that the combination of references does not teach or suggest that 2-deoxy-2-[18F]fluorocellobiose (FCB) is metabolized by fungal β-glucosidases to produce glucose and FDG and as a result specifically label fungal molds but not bacteria or yeast. FCB is highly selective for imaging A. fumigatus over other PET ligands and highly selective of imaging metabolically active (live) A. fumigatus over heat killed A. fumigatus. In vitro assays showed higher uptake of FCB in A. fumigatus cultures compared to FDG, FDS, and F-Rham. In vivo tests demonstrated that FCB shows highest accumulation in sites live A. fumigatus infection compared to FDS and F-Rham and demonstrated that FCB can differentiate live A. fumigatus from heat killed A. fumigatus while FDG cannot. FCB is surprisingly highly selective for differentiating A. fumigatus from bacteria and is highly selective for imaging A. fumigatus over FDS. Tests demonstrate that FCB is highly selective for A. fumigatus over bacteria while FDS is highly selective for gram negative bacteria compared to A. fumigatus. FCS is surprisingly selective for molds producing cellobiose-specific β-glucosidase enzymes. Tests showed that FCB can differentiate between intracellular and extracellular β-glucosidase enzyme activity even if β-glucosidase enzyme is present in both locations. Data demonstrate that FCB is a highly specific PET ligand that can detect liver Aspergillus infections and Mucorales sp (R oryzae) since those molds can convert FCB into glucose and FDG. FCB is a highly specific PET ligand that can distinguish live mold infections from non-metabolically active infections. The data demonstrate that FCB can differentiate molds with extracellular β-glucosidase activity from molds with intracellular β-glucosidase activity due to difference between intracellular and extracellular metabolism of FCB. FB is surprisingly selective for molds of yeasts. FCB can be used to specifically differentiate mold infections from non-cellulolytic fungal yeast infection like infections with C. albicans.
The Dr. Hammoud declaration filed 31 Oct. 2025 has been fully considered but it is not persuasive. Namavari provides for the PET imaging probe
PNG
media_image1.png
179
310
media_image1.png
Greyscale
that differs from the PET imaging probe of claim 60 as amended only by being a spatial isomer at the glycosic bond: maltose has an α(1[Wingdings font/0xE0]4)glycosidic bond and cellobiose has a β(1[Wingdings font/0xE0]4). This difference results in unique properties such as the ability for humans to digest maltose but not cellobiose. Jain teaches and motivates methods of detecting fungi, the methods comprising administering to a labeled substrate wherein the labeled substrate is solely utilized the metabolism of the infectious microorganism. At [0038], Jain teaches cellobiose as a substrate useful for the detection of the infectious disease. Jain teaches 18F has an advantageously detectable label. Wojtusik teaches that cellobiose is metabolized by BG enzymes present in A. fumigatus. BG act on the hydrolysis of glycosidic bonds which produces the release of nonreducing glycosyl residues. A person of ordinary skill in the art knowing the structure of the obvious FCB would have understood that BG would act on FCB by hydrolyzing the glycosidic bond to release glucose and FDG, which is a well-known substrate for the PET detection of pathogenic fungi. See Ankrah (cited below). Ankrah not being used in a rejection because it is cumulative. It would have been obvious to a person of ordinary skill in the art before the effective filing date to modify Namavari by spatially isomerizing the glycosidic bond of 2-18F-fluoromaltose to form 2-18F-cellobiose and then contact fungus expected to metabolize the 2-18F-cellobiose such as A. fumigatus thereby detecting the fungus as taught by Jain and Wojtusik because the isomerizing and contacting would have been expected to enable selective PET detection of pathogenic fungi such as A. fumigatus. Instant claim 60 broadly recites “contacting the fungus’ and “detecting the fungus”. The showing of unexpected results must be reviewed to see if the results occur of the entire claimed range. See In re Clemens, 622 F.2d 1029, 1036, 206 USPQ 289, 296 (CCPA 1980). The Dr. Hammoud declaration does not evidence or suggest that FCB is capable of selectively detecting any fungus including fungi incapable of metabolizing FCB. For example, the Dr. Hammoud declaration provides an experiment comparing the uptake of FCB by A. fumigatus, R. oyrzae, and C. albicans. Unlike A. fumigatus and R. oryzae, no uptake of breakdown of FCB was observed in C. albicans. Accordingly, the Dr. Hammoud declaration shows that the unexpected results do not occur over the entire scope of claim 60. Additionally, the Dr. Hammoud declaration does not establish the following (i) if FCB is highly selective for imaging Mucormycetes over other PET ligands, and (ii) if FCB is surprisingly highly selective for differentiating Mucormycetes from bacteria. Mucormycetes refers to groups of molds—such as Rhisopus, Mucor, and Lichtheimia– found throughout the natural environment. The Dr. Hammoud declaration only provides data for R. oryzae, which may only extend to Rhisopus sp. Accordingly, the Dr. Hammoud declaration does not demonstrate that the results occur over the entire scope of claim 61.
Response to Arguments
In view of Applicants amendments, the rejection of claims 45,50, 53, and 55-59 under 35 USC 103 as being unpatentable over Namavari et al. (US 2014/0314671 A1; published 23 Oct. 2014), in view of McCarter et al. (Carbohydrate Res.; published 1993) is withdrawn.
In view of Applicants amendments, the rejection of claims 45, 47, 51-52, 58-60, and 62-64 under 35 USC 103 as being unpatentable over Namavari et al. (US 2014/0314671 A1; published 23 Oct. 2014), in view of Liu et al. (Chem. Eur. J.; published 2016) and Lee et al. (Proc. Royal Irish Acad.; published 1977), in further view of Jain et al. (US 2015/0250906 A1; published 10 Sep. 2015) is withdrawn.
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) 60-64 is/are rejected under 35 U.S.C. 103 as being unpatentable over Namavari et al. (US 2014/0314671 A1; published 23 Oct. 2014), in view of McCarter et al. (Carbohydrate Res.; published 1993), in further view of Wojtusik et al. (Chem. Engin. Res. Des.; published 2018) and Jain et al. (US 2015/0250906 A1; published 10 Sep. 2015) for the reasons cited in the Office action filed on 5 Jun. 2025.
Applicants Arguments
Applicants refer to the Dr. Hammoud declaration. Applicants assert that Namavari in view of McCarter, Wojtusik, and Jain does not teach or suggest using FCB for imaging fungi. The Dr. Hammoud declaration establishes that while Wojtusik discloses that a β-glucosidase from A. fumigatus hydrolyzes cellobiose to glucose, Wtjusik does not teach or suggest whether an 18F-labeeld cellobiose was used, the result would be glucose and FDG instead of two glucose molecules. Wojtusik does not teach or suggest that FDG cannot be used for energy production by the fungus and would instead accumulate inside the fungal cell due to phosphorylation, resulting in radioactive signal that can be detected as a image using PET scanning. Wotjusik does not teach or suggest if there would be specific uptake and retention of newly for FDG in the fungus, which is required for imaging fungi. Jain only provides data on simple uptake and retention of FDS in bacteria. Jain cannot teach or suggest FCB can be used to image fungi.
Applicant's arguments filed 31 Oct. 2025 have been fully considered but they are not persuasive. The Dr. Hammoud declaration is ineffective for the reasons discussed above. As discussed above, Jain and Wojtusik provide adequate reason and motivation to modify the 2-18F-fluoromaltose in Namavari that gets metabolized in humans by forming the spatial isomer FCB, which does not get metabolized by human subjects, and then contact the FCB with a fungus expected to metabolize the FCB using a BG that hydrolyzes the FCB to glucose and FDG. A person of ordinary skill in the art would have been motivated to administer the obvious FCB to a fungus expected to selectively metabolize FCB optionally in a human host in order to gain the advantages of in vitro and in vivo PET detection of pathogenic fungi whereby enabling diagnosis, localization and monitoring of potentially fatal fungal infections.
New Grounds of Rejection
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.
Claims 62-64 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. In claim 62, the recitation of “one or more compounds to a subject” is indefinite because claim 62 is dependent to claim 60, which requires the compound having the structure recited in claim 60. It is not clear if claim 62 further limits claim 60 since claim 62 does not require administering the compound recited in claim 60 but instead requires administering one or more compounds to a subject. Claims 63 and 64 depend to claim 62 and fall therewith.
Technical Background Section
Ankrah et al. (Curr. Pharmaceutical Des.; published 2018; see attached 892) is being made of record; however, Ankrah et al. is not being used in a rejection because it is cumulative.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SEAN R DONOHUE whose telephone number is (571)270-7441. The examiner can normally be reached on Monday - Friday, 8:00 - 5:00 EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Michael Hartley can be reached on (571)272-0616. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/Michael G. Hartley/Supervisory Patent Examiner, Art Unit 1618
/SEAN R. DONOHUE/
Examiner, Art Unit 1618