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 the Application
Claims 1-8 are under examination.
Specification - Abstract
The abstract of the disclosure does not commence on a separate sheet in accordance with 37 CFR 1.52(b)(4) and 1.72(b). A new abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text.
Applicant is reminded of the proper language and format for an abstract of the disclosure.
The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details.
The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc. In addition, the form and legal phraseology often used in patent claims, such as “means” and “said,” should be avoided.
Specification - Objections
The disclosure is objected to because of the following informalities: chemical structures are blurry and difficult to read.
Appropriate correction is required.
Claim Objections
Claim 3 is objected to because of the following informalities: “potentiometric titer” is misspelled as “potentiometric title”. Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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.
Claim 2 recites the limitation "the amount" in line 2. There is insufficient antecedent basis for this limitation in the claim.
Claim 7 is 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.
The term “an effective amount” in claim 7 is a relative term which renders the claim indefinite. The term “an effective amount” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. While the disclosure discusses prior art formulations and their doses that are effective, the disclosure does not provide examples of "an effective amount" of the claimed formulations and is therefore rendered indefinite.
Claim 8 recites the limitation "the production" in line 2. There is insufficient antecedent basis for this limitation in the claim.
Claim Interpretation
Claim 2 recites compositions in the alternative for both indocyanine green and sodium fluorescein. The examiner notes that the amount of indocyanine green and sodium fluorescein are not claimed as interdependent. For the purposes of examination, the examiner interprets any prior art reading on indocyanine green and sodium fluorescein amounts in the claimed ranges as potential prior art.
Claim 3 recites “potentiometric title”, the examiner interprets this as “potentiometric titer” for the purposes of examination.
Claim 3 recites, “0% ≤ NaI ≤ 2.5%” but does not specify units in the claim. However, the examiner acknowledges that in the specification, the percent NaI is used in two ways: (w/w) and (w/v). The examiner will consider either measurement for prior art.
Claim 7 recites “an effective amount”. As discussed above, an effective amount is a relative term. Given that neither the claims nor specification discuss the effective amount of the claimed composition, the examiner interprets “an effective amount” to mean a high enough dose to be visible in imaging in ophthalmology. Accordingly, any prior art that reads on ophthalmology imaging with a dose high enough to be visible reads on this claim.
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) in further view of 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 or 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 or 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 “an effective amount” 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]).
Claim(s) 3 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) in further view of Alam, et al. (US 2003/0060718 A1) in further view of Fang et al. (Fang, X., et al. One-step condensation synthesis and characterizations of indocyanine green, Results in Chemistry, 2021, 3, 100092).
As to claim 3, Freeman and Alam teach compositions made from a powder form of indocyanine green.
Freeman and Alam do not teach synthesis without sodium iodide.
Fang, et al. (hereafter referred to as Fang) is drawn to the synthesis of indocyanine green for many uses including those in angiography (title, abstract (lines 1-2), introduction (col 1, line 14). Particularly, Fang teaches the synthesis of indocyanine green without using NaI recrystallization technique (pg 2, col 1, lines 8-13).
The scope and content of the Fang, Alam, and Freeman, 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 product of indocyanine green. And, there were design incentives of obtaining indocyanine green in fewer synthetic steps with high yield (Fang, pg 2, col 1, lines 1-5) which would have prompted adaptation of the known composition of indocyanine green with fluorescein. And, the differences between the claimed invention and the prior art were encompassed in known variations or in a principle known in the combined teachings of Fang, Alam, and Freeman. Therefore, a person of ordinary skill in the art, in view of the identified design incentives, 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)(E).
Regarding the range of NaI, Fang teaches the synthesis of indocyanine green without the use of sodium iodide (pg 2, col 1, lines 8-13, and Fig 1). A synthesis without sodium iodide contains 0% NaI. Therefore, the ranges overlap with the instant claimed range of 0 ≤ NaI ≤ 2.5%. In the case where the claimed ranges “overlap or lie inside ranges” disclosed by the prior art” a prima facie case of obviousness exists. See MPEP 2144.05(I).
Regarding the method of measuring sodium iodide, the “base” composition may be measured in such a way so as to improve the composition readiness for use in a subject in need thereof. The applicant is using a known technique, “potentiometric titer with silver electrode in accordance with USP monograph” that is applicable to solutions for use in subjects in need thereof. Therefore, one of ordinary skill in the art would have recognized that applying the known technique would have yielded predictable results and resulted in a composition ready for a subject in need thereof. In such cases, it is considered obvious to adopt techniques from other environments. See MPEP 2143(I)(D).
Conclusion
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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