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 .
Status of Application
Applicant’s amendments of claim(s) 1-2 and 7-8 in the reply filed on 06/11/2026
is acknowledged.
Applicant’s cancellation of claim(s) 3 in the reply filed on 06/11/2026 is
acknowledged.
Claims 1-2 and 4-8 are under examination.
Applicant's arguments, filed 06/11/2026, 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objections not reiterated from previous office actions are hereby withdrawn.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 Interpretation
Claim 1 recites “obtained through freeze-drying a solution containing said indocyanine green and said sodium fluorescein”. The examiner interprets this as product-by-process language. Even though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process. See MPEP 2113(I). Therefore, any prior art reading on the solid composition, reads on this claim.
Claim 7 recites “effective to be visible in imaging ophthalmology”. The examiner notes that the claim does not list specific values. For the purposes of examination, the examiner interprets this phrase to mean any prior art which uses the compounds to be visible in the imaging technology reads on this phrase.
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) 1-2 and 4-8 is/are rejected under 35 U.S.C. 103 as being unpatentable over Freeman et al. (Freeman, W. R., et al. Simultaneous Indocyanine Green and Fluorescein Angiography Using a Confocal Scanning Laser Ophthalmoscope, Arch Ophthalmol. 1998, 116, 455-463) and Alam, et al. (US 2003/0060718 A1).
Freeman et al. (hereafter referred to as Freeman) is drawn to simultaneous administration of fluorescein and indocyanine green for use in ophthalmology (e.g. title, abstract (lines 25-27); pg 1, pg 456, col 2, lines 5-7; pg 456, col 2, lines 13-16; pg 457, col 1, lines 1-2). Freeman teaches that combining a solid indocyanine green with aqueous fluorescein into one dose is advantageous for rapid, safe, and convenient treatment for patients (abstract, col 2, line 10-12). Freeman teaches the simultaneous ICG and fluorescein angiography can be performed rapidly, safely, and conveniently (abstract, col 2, lines 10-12). Further, Freeman teaches combining the indocyanine green with sodium fluorescein is advantageous due to reduced time required (pg 456, col 1, lines 56-58) and improved assessment of imaging data (pg 456, col 2, lines 47-54).
As to claim 1, Freeman teaches a composition indocyanine green and sodium fluorescein (pg 456, col 2, lines 6-14).
Freeman does not teach a solid composition of indocyanine green and sodium fluorescein.
Alam et al. (hereafter referred to as Alam) is drawn to compositions for improved stability and administration of indocyanine green for use in many fields including within ophthalmology (e.g. title; abstract (lines 1-5); pg 1, para [0006], lines 1-7; pg 1, para [0018], lines 1-8; pg 10-13, claims 1-96). The works of Freeman and Alam are drawn to compositions with indocyanine green for use within the similar fields, a person of ordinary skill in the art would be motivated to combine elements from each application.
Alam teaches that indocyanine green is unstable in aqueous solutions and is therefore most commonly in lyophilized form (pg 1, para [0003], lines 4; pg 2, para [0020], lines 2-4). Given that Freeman teaches the base composition of indocyanine green with fluorescein (title, abstract (lines 25-27); pg 456, col 2, lines 5-7, pg 456, col 2, lines 13-16; pg 457, col 1, lines 1-2), and that Alam teaches indocyanine green is not stable for prolonged times in aqueous solutions and should be stored as a solid one of ordinary skill in the art could have applied the known “improvement” in Alam of lyophilizing indocyanine green solutions in the same way to the “base” composition in Freeman of indocyanine green with fluorescein and the results would have been predictable to one of ordinary skill in the art. See MPEP 2143(I)(C).
Alternatively, the scope and content of the prior art, whether in the same field of endeavor as that of the applicant’s invention or a different field of endeavor, included a similar or analogous composition and means for forming it. There is an incentive to maintain the indocyanine green as a lyophilized composition due to its aqueous instability which would have prompted adaptation of the known lyophilization practice for indocyanine green. The differences between the claimed solid composition of indocyanine green and fluorescein and the aqueous composition are encompassed as a known principle in the prior art. Therefore, one of ordinary skill in the art, in view of the stability pressure of indocyanine green and convenience pressures, could have implemented the claimed variation of the prior art, and the claimed variation would have been predictable to one of ordinary skill in the art. See MPEP 2143(I)(F).
As to claim 2, Freeman teaches a composition containing 25 mg of indocyanine green and 500 mg of sodium fluorescein (page 456, col 2, lines 14-15). 25 mg of indocyanine green is listed as an option in the claimed range of indocyanine green (2.5, 5, 10, 25, 50, or 100 mg) of claim 2. And, 500 mg of sodium fluorescein is listed as an option in the claimed range of sodium fluorescein (0.1, 0.2, 0.4, 2.5, 2.0, 1.25, or 1 g). Since claim 1 is rendered obvious by Freeman and Alam and claim 2 is dependent on claim 1, claim 2 is rendered obvious by the combined teachings of Freeman and Alam.
As to claim 4, Freeman teaches a composition containing 25 mg of indocyanine green and 500 mg of sodium fluorescein (page 456, col 2, lines 14-15). The claimed composition contains 5 mg of indocyanine green and 200 mg of sodium fluorescein.
Generally, differences in concentration or temperature between the claimed invention and prior art will not support patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration is critical. See MPEP 2144(II)(A). Additionally, where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation. See MPEP 2144.05(II)(A). It would not have been inventive for the skilled artisan to have discovered the optimum or workable volume and concentration of these components via routine experimentation.
As to claim 5, Freeman teaches an aqueous solution formed by compounds of formula (IA) and (IB) (pg 456, col 2, lines 13-15).
Freeman does not teach lyophilization of formula (IA) or formula (IB).
Alman teaches lyophilization of compound of formula (IA) (pg 6, paragraph [0067], lines 1-8).
Alman does not teach lyophilization of formula (IB).
However, Alman teaches to improve stability by lyophilizing solutions containing indocyanine green. Alam teaches that indocyanine green is preferred in lyophilized form for long-term storage (pg 6, col 2, paragraph [0067]).
Given that Freeman teaches the base composition of indocyanine green with fluorescein, and that Alam teaches indocyanine green is not stable for prolonged times in aqueous solutions and should be stored as a solid, one of ordinary skill in the art could have applied the known “improvement” of lyophilizing indocyanine green solutions in the same way to the “base” composition of indocyanine green with fluorescein and the results would have been predictable to one of ordinary skill in the art. See MPEP 2143(I)(C).
Alternatively, the scope and content of the prior art, whether in the same field of endeavor as that of the applicant’s invention or a different field of endeavor, included a similar or analogous composition and means for forming it. There is an incentive to maintain the indocyanine green as a lyophilized composition due to its aqueous instability which would have prompted adaptation of the known lyophilization practice for indocyanine green. The differences between the claimed solid composition of indocyanine green and fluorescein and the aqueous composition are encompassed as a known principle in the prior art. Therefore, one of ordinary skill in the art, in view of the stability pressure of indocyanine green and convenience pressures, could have implemented the claimed variation of the prior art, and the claimed variation would have been predictable to one of ordinary skill in the art. See MPEP 2143(I)(F).
As to claim 6, Alam teaches microfiltration of the aqueous solution before lyophilization (pg 6, para [0067], lines 3-4).
As to claim 7, Freeman teaches a method of diagnostic imaging in ophthalmology to a subject in need thereof (pg 456, col 2, lines 2-21), administering a dose (abstract, col 1, lines 12-15), and effective to be visible in imaging ophthalmology to a subject as discussed in the claim interpretation above (pg 456, col 2, lines 2-21; pg 458, Figure 2; pg 459, Figure 3; pg 460, Figures 4-5; pg 461, Figure 6; pg 462, Figure 7).
As to claim 8, Alam teaches a kit comprising a solid composition and a vial of sterile water suitable for production of an intravenous injection solution (pg 2, col 1, para [0020]-[0021]).
Response to Arguments
Applicants state that Freeman is completely silent with regard to a solid kit consisting of the two freeze-dried powders obtained from a solution containing both. The applicants acknowledge Freeman describes using indocyanine green and sodium fluorescein simultaneously in ophthalmology and further acknowledge that freeze-dried indocyanine green is dissolved in a solution with fluorescein before injection. Further, applicants acknowledge that indocyanine green is unstable in aqueous solutions and storage of a mixture of indocyanine green and sodium fluorescein in solution for a prolonged period of time would be impossible.
Further, the applicants state Alam is completely silent with regard to the simultaneous use of the two elements, but only describes that indocyanine green can be freeze-dried. The applicants acknowledge that freeze-drying indocyanine green is well-known in the art.
The applicants argue that the combination of the teachings of Freeman and Alam does not describe the freeze-drying of an aqueous solution consisting of indocyanine green and sodium fluorescein in appropriate quantities to obtain a solid, soluble, stable, and ready-to-use composition as presently claimed.
Respectfully, the applicants’ arguments are not persuasive. While each individual references does not explicitly describe the freeze-drying of an aqueous solution consisting of both indocyanine green and sodium fluorescein to obtain a solid composition, the combination of the two arts would have rendered the freeze-drying of a solution containing indocyanine green prima facie obvious. The Supreme Court in KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007) identified a number of rationales to support a conclusion of obviousness which are consistent with the proper "functional approach" to the determination of obviousness as laid down in Graham. The key to supporting any rejection under 35 U.S.C. 103 is the clear articulation of the reason(s) why the claimed invention would have been obvious. See MPEP 2143. The court set forth a list of non-exhaustive list of rationales that articulate a finding of obviousness. In the instant case, the examiner articulated two rationales that a person of ordinary skill in the art would have combined the references of Freeman and Alam to obtain the solid composition to obtain compositions in the appropriate quantities to obtain a solid, soluble, stable and ready-to-use composition.
These rationales are restated here with emphasis for clarity. “Given that Freeman teaches the base composition of indocyanine green with fluorescein (title, abstract (lines 25-27); pg 456, col 2, lines 5-7, pg 456, col 2, lines 13-16; pg 457, col 1, lines 1-2), and that Alam teaches indocyanine green is not stable for prolonged times in aqueous solutions and should be stored as a solid one of ordinary skill in the art could have applied the known “improvement” in Alam of lyophilizing indocyanine green solutions in the same way to the “base” composition in Freeman of indocyanine green with fluorescein and the results would have been predictable to one of ordinary skill in the art. See MPEP 2143(I)(C).
Alternatively, the scope and content of the prior art, whether in the same field of endeavor as that of the applicant’s invention or a different field of endeavor, included a similar or analogous composition and means for forming it. There is an incentive to maintain the indocyanine green as a lyophilized composition due to its aqueous instability which would have prompted adaptation of the known lyophilization practice for indocyanine green. The differences between the claimed solid composition of indocyanine green and fluorescein and the aqueous composition are encompassed as a known principle in the prior art. Therefore, one of ordinary skill in the art, in view of the stability pressure of indocyanine green and convenience pressures, could have implemented the claimed variation of the prior art, and the claimed variation would have been predictable to one of ordinary skill in the art. See MPEP 2143(I)(F).” As described above, and in the above rejections, the combination of Freeman and Alam teach the appropriate quantities to obtain a solid, soluble, stable, and ready-to-use composition.
The applicants argue that although freeze-drying indocyanine green is known in the art, freeze-drying indocyanine green with another element was not known in the art and that freeze-drying these elements to obtain a powder with the solubility characteristic achieved is not a given.
Respectfully, the applicants’ arguments are not persuasive. While the examiner acknowledges that the teachings of Freeman and Alam do not teach freeze-drying indocyanine green with another compound, they do teach the use of the compounds together and the instability of indocyanine green (as noted in the rejections above). Further, a person of ordinary skill in the art would expect to achieve a water-soluble material upon freeze-drying given that each material used is water-soluble. Furthermore, indocyanine green is known to freeze-dry into a powder and sodium fluorescein is an organic salt which is known to be a water-soluble salt. Therefore, a person of ordinary skill in the art would expect to achieve claimed solubility characteristics.
The applicants argue that freeze-drying can produce oils, sticky powders, and pitch. And, these results depend greatly on what is being freeze-dried and not just from the freeze-drying conditions.
Respectfully, the applicants’ arguments are not persuasive. While materials can influence whether freeze-drying can produce oils, sticky powders, and pitch, the materials used are both water soluble and indocyanine green is a known freeze-dried powder and sodium fluorescein is an organic salt. Therefore, a person of ordinary skill in the art would expect the combination of a salt and a powder to dissolve and freeze-dry into a water-soluble powder.
The applicants argue that a person of ordinary skill in the art would not have arrived at the claimed invention by simply combining and modifying Freeman and Alam without undue experimentation and with a reasonable expectation of success.
Respectfully, the applicants’ arguments are not persuasive. With respect to “undue experimentation”, the argument is not persuasive because undue experimentation is a Wands factors for testing whether the instant application complies with enablement. Within 30 U.S.C 103 rejections, even if prior art disclosure is not enabled and “undue experimentation” was needed, it is still prior art for all that it teaches. See MPEP 2121.01(II). Additionally, where prior art discloses the structure of the claimed compound, evidence must be shown that attempts to prepare that compound were unsuccessful before the relevant time to show inoperability. See MPEP 2121.02(II).
With respect to “a reasonable expectation of success”, a standard for identifying a reasonable expectation is necessary for a prima facie obviousness rejection. The likelihood of success in combining or modifying prior art disclosures to meet the limitation of the claimed invention is set forth in KSR. See MPEP 2143(I)(A-G). Additionally, a reasonable expectation of success can be implicitly shown via the prior art teachings or as part of the obviousness analysis. See the KSR rationale used in the rejections above. Furthermore, conclusive proof of efficacy is not required to show a reasonable expectation of success. See MPEP 2143.02(I).
The applicants argue that it was not predictable whether indocyanine green and sodium fluorescein would have maintained their HPLC quality when freeze-dried simultaneously.
Respectfully, the applicants’ arguments are not persuasive. The HPLC quality of the compounds when freeze-dried simultaneously is not a claim limitation. Furthermore, indocyanine green is known in the art to maintain stability in the freeze-dried form and sodium fluorescein is known to be stable both in solution and as a powder. Therefore, a person of ordinary skill in the art would have recognized that the result of the combination was predictable.
The applicants argue that the present invention, characterized by a homogenous, soluble powder, already weighted in the appropriate therapeutic quantities and ready-to-use, is surprising and unexpected and cannot be extrapolated by the combination of Freeman and Alam.
Respectfully, the applicants’ arguments are not persuasive. Based on the KSR arguments, the combination of Freeman and Alam render obvious homogenous, soluble power, weighted in the appropriate quantities and ready-to-use as discussed above. Generally, any differences between the claimed invention and the prior art may be expected to result in some differences in properties. The issue is whether the properties differ to such an extent that the difference is really unexpected. allegations of unexpected results must be accompanied by evidence. See MPEP 716.02. Evidence to unexpected results should show I) greater than expected results, II) superiority of a property shared with the prior art, III) presence of an unexpected property, or IV) absence of an expected property. The applicant has not presented evidence that the claimed invention meets one of these four categories.
The rejections are maintained.
Conclusion
No claims are allowed.
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 Evan M Lewoczko whose telephone number is (571)272-9830. The examiner can normally be reached Monday-Friday 9-5PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sahana Kaup can be reached at (571) 272-6897. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/EVAN M LEWOCZKO/Examiner, Art Unit 1612
/SAHANA S KAUP/Supervisory Primary Examiner, Art Unit 1612
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