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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 4/9/2026 has been entered.
Amendments
Applicants’ amendments to the claims filed 4/9/2026 have been entered. Any objection\rejections from the previous office action filed 1/9/2026 not addressed below has been withdrawn.
Claim Objections
Applicant is advised that should claim 38 be found allowable, claim 39 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
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) 1,3-4,6,11,15,28 and 33-40 is/are rejected under 35 U.S.C. 103 as being unpatentable over Aubin-Walker et al. (US 2019/0241956 A1) in view of Kjaer et al. (WO 2016/041558 A1), cited by applicants, for the reasons set forth in the previous action filed 9/3/2025.
Aubin-Walker teaches lyophilized formulations (considered to have essentially no or only trace amounts of water) containing a red dye probe, including Cy5 bound to a carrier molecule including targeting peptides such as antibodies, the formulation further comprising surfactant including polysorbate (meeting claim 6 and 15) and phosphate buffer. See entire disclosure, especially abstract, [0018],[0025]-[0027], [0042],[0049]-[0052] and claims. Regarding the claimed lycoprotectants, Aubin-Walker discloses use of glycine as a lyoprotectant. See [0050]. Regarding the claimed pH range, Aubin-Walker discloses using buffers, including phosphate buffers, at a pH range from about 6.5 to about 7.5, overlapping and incorporating the claimed range. A prima facie case of obviousness typically exists when the range of a claimed composition lies inside the range disclosed in the prior art, such as in the instant rejection. Therefor, based on the described overlap above, the instant claims would have been obvious to one of ordinary skill in the art. MPEP § 2144.05. Regarding 34, Polysorbate-20 is listed at [0005].
The reference is silent with respect to the elected fluorophore-receptor targeting component ICG-Glu-Glu-AE105.
Kjaer is used for its disclosure that ICG-Glu-Glu-AE105 was a known fluorophore conjugate targeting cell surface receptor uPAR before the time of the claimed invention. See entire disclosure, especially abstract and claims. The conjugate Kjaer was capable of carrying the detectable and imageable label allowing for clear tumor delineation both in vitro and in vivo through targeting to uPAR expressing tumor cells. The major advantages of the conjugate are tumor specificity and that it particularly accumulates in the invasive front of cancers. The conjugate clearly indicated where the active border of a tumor is relative to surrounding healthy tissue. This allowed surgeons to see exactly where the tumor stops and remove only the tumor and no surrounding tissue. If no tissue lighting is left behind the cancer was successfully removed. See page 1 lines 7-12, page 2 lines 13-19, page 3 lines 12-19.
Since Aubin-Walker already teaches use of fluorophore-targeting conjugates one of ordinary skill would have a high expectation of success in adding ICG-Glu-Glu-AE105 to the lyophilized composition. Reason to make such a modification stems from the noted advantageous of ICG-Glu-Glu-AE105, including specific targeted delivery to tumors overexpressing uPAR, allowing surgeons to visualize removal of the tumor. Thus the claimed invention would have been prima facie obvious since all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions and the combination would have yielded predictable results to one of ordinary skill in the art at the time of the invention.
Regarding claims 3-4 which recite absorption maximum for the composition, it follows that since the composition of Aubin-Walker and Kjaer is within the same scope of the claims and features the same fluorophores, it will feature the same properties including its absorption spectra peaks. The absorption maximum is the natural result that would occur from combining the two references.
Regarding the concentration of ICG-Glu-Glu-AE105, while Kjaer suggest the dosage amount of the conjugate is from 0.1-1000 mg per subject it is silent with respect to the amount in mg/ml as recited. However, one of ordinary skill in the art would optimize the amount of fluorophore-targeting protein conjugate in an amount effective to visualize the tumor without adverse side effects, commensurate with a reasonable risk/benefit ratio. It has also been held that the mere selection of proportions and ranges is not patentable absent a showing of criticality. See In re Russell, 439 F.2d 1228 169 USPQ 426 (CCPA 1971).
Claim(s) 1,3-4,6,11,14-15,28 and 33-40 is/are rejected under 35 U.S.C. 103 as being unpatentable over Aubin-Walker et al. (US 2019/0241956 A1) in view of Kjaer et al. (WO 2016/041558 A1), cited by applicants, in view of Pyne et al. “Solute Crystallization in Mannitol–Glycine Systems-Implications on Protein Stabilization in Freeze-Dried Formulations, JOURNAL OF PHARMACEUTICAL SCIENCES, VOL. 92, NO. 11, NOVEMBER 2003, for the reasons set forth in the previous action filed 9/3/2025.
The combination of Aubin-Walker and Kjaer is disclosed above. The combination is silent with respect to use of mannitol as a lyoproctectant.
Pyne is used for the disclosure within that sodium phosphate buffer in combination with mannitol and glycine lyoprotectants were well known to stabilize lyophilized protein formulations. See entire disclosure, especially abstract, tables 1-2 and last ¶.
Since Aubin Walker already teaches use of buffers and lyoprotectants in its formulation, including phosphate buffer and glycine, one of ordinary skill in the art would have a very high expectation of success in adding any of the excipients of Pyne, including sodium phosphate mannitol lyoproctectant to the lyophilized formulation. It is obvious to those skilled in the art to substitute one known equivalent for another. See In re Omeprazole Patent Litigation, 483 F.3d 1364, 1374 (Fed. Cir. 2007) (“[T]his court finds no . . . error in [the] conclusion that it would have been obvious to one skilled in the art to substitute one ARC [alkaline reactive compound] for another.”). The reason for specifying it flows from its having been used in the prior art, and from its being recognized in the prior art as useful for the same purpose. Thus the claimed invention would have been prima facie obvious since all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions and the combination would have yielded predictable results to one of ordinary skill in the art at the time of the invention.
The combination above is silent with respect to the amounts of mannitol and glycine recited in claim 14. However, the preparation of lyophilized compositions having variable amount of lyoproctectant is within the level of skill of one having ordinary skill in the art at the time of the invention. One of ordinary skill would adjust the amount of lyoproctectants such that the formulation is stable. It has also been held that the mere selection of proportions and ranges is not patentable absent a showing of criticality. See In re Russell, 439 F.2d 1228 169 USPQ 426 (CCPA 1971).
Claim(s) 1,3-4,6,11,14-15,28 and 33-40 is/are rejected under 35 U.S.C. 103 as being unpatentable over Jochheim et al. (WO 2015/042202) in view of Kjaer et al. (WO 2016/041558 A1), for the reasons set forth in the previous action filed 9/3/2025.
Jochheim teaches chlorotoxin conjugates with reporter molecule including fluorescent dyes such as ICG in lyophilized formulations that include mannitol, glycine, buffer, including phosphate buffer and surfactant including polysorbate; the composition had a physiological pH of 6.8. See entire disclosure, especially abstract and claims, especially 1,102,121,143-145,162-168,307. While the pH is just outside of the claimed range since the invention and Jockheim are said to have a physiological pH, one of ordinary skill in the art would presume the compositions to have the same or similar properties. A prima facie case of obviousness exists where the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have the same properties. See MPEP § 2144.05.
The reference while teaching protein ICG conjugates is silent with respect to the use of ICG-Glu-Glu-AE105.
Kjaer is used for its disclosure that ICG-Glu-Glu-AE105 was a known fluorophore conjugate targeting cell surface receptor uPAR before the time of the claimed invention. See entire disclosure, especially abstract and claims. The conjugate Kjaer was capable of carrying the detectable and imageable label allowing for clear tumor delineation both in vitro and in vivo through targeting to uPAR expressing tumor cells. The major advantages of the conjugate are tumor specificity and that it particularly accumulates in the invasive front of cancers. The conjugate clearly indicated where the active border of a tumor is relative to surrounding healthy tissue. This allowed surgeons to see exactly where the tumor stops and remove only the tumor and no surrounding tissue. If no tissue lighting is left behind the cancer was successfully removed. See page 1 lines 7-12, page 2 lines 13-19, page 3 lines 12-19.
Since Jochheim already teaches use of ICG-protein targeting conjugates one of ordinary skill would have a high expectation of success in adding ICG-Glu-Glu-AE105 to the lyophilized composition. Reason to make such a modification stems from the noted advantageous of ICG-Glu-Glu-AE105, including specific targeted delivery to tumors overexpressing uPAR, allowing surgeons to visualize removal of the tumor. Thus the claimed invention would have been prima facie obvious since all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions and the combination would have yielded predictable results to one of ordinary skill in the art at the time of the invention.
The combination above is silent with respect to the amounts of mannitol and glycine recited in claim 14. However, the preparation of lyophilized compositions having variable amount of lyoproctectant is within the level of skill of one having ordinary skill in the art at the time of the invention. One of ordinary skill would adjust the amount of lyoproctectants such that the formulation is stable. It has also been held that the mere selection of proportions and ranges is not patentable absent a showing of criticality. See In re Russell, 439 F.2d 1228 169 USPQ 426 (CCPA 1971).
Regarding claims 3-4 which recite absorption maximum for the composition, it follows that since the composition of Jochheim and Kjaer are within the same scope of the claims and features the same fluorophores, it will feature the same properties including its absorption spectra peaks.
Response to Arguments
Applicant's arguments filed 4/9/2026 have been fully considered but they are not persuasive.
Applicants assert the claimed combination provides an optical composition with regards to stability, pharmacokinetic profile, target selectivity, toxicity, water content, reconstitutability etc. Applicants pick on the secondary reference Kjaer for not teaching how to optimize a lyophilized composition with the desirable inventive properties.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Clearly Kjaer was used for its teaching of ICG-Glu-Glu-AE105 and was not used to pick up the other ingredients which are covered by the primary references or Pyne.
In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., stability over time) are not recited in the rejected claim(s). 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). Secondly since the composition of the combined teachings is within the claimed scope any property discovered by applicants is merely the natural result from the combination.
Applicants assert new claims 38-40 require specific combinations of lycoprotectants and the primary references do not point to the specific combination.
The lycoprotectants are all covered in the combination of Aubin-Walker and Pyne and Joccheim alone. Since these compounds are all listed as being used for the same purpose as lyoprotectants one of ordinary skill could combine them to serve the same purpose. It is generally considered to be prime facie obvious to combine compounds each of which is taught by the prior art to be useful for the same purpose in order to form a composition that is to be used for an identical purpose. The motivation for combining them flows from their having been used individually in the prior art, and from them being recognized in the prior art as useful for the same purpose.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JAMES W ROGERS whose telephone number is (571)272-7838. The examiner can normally be reached 9:30-6:00 PM.
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 at 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 published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/JAMES W ROGERS/ Primary Examiner, Art Unit 1618
Prosecution Insights