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 .
Claim Rejections - 35 USC § 112 – Indefiniteness
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 2, 4, 7 and 13 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.
Claim 1, from which all other claims depend, recites a solid composition that must contain 4% or less water. Each of the rejected claims requires that the composition be an aqueous solution, which is not a solid but a liquid and given the upper limit on the water content, would need to contain more than 4% water in order to be an aqueous solution. Each claim appears to require this form and is not reciting that if the solid composition was dissolved in water, then the conditions recited would be met. The latter interpretation would result in proper dependent claims but the claims do not clearly indicate that each of these claims is referencing what would happen should the solid composition being claimed be exposed to water to form an aqueous solution.
Please clarify.
Claim 9 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.
Claim 9 references “the total amount of related substances” but neither the claims nor the specification define to what substance(s) the phrase “related substances” refers to and/or what type of relationship(s) are encompassed by this phrase to reasonably apprise one of ordinary skill in art as to the metes and bounds of the claims.
Please clarify.
Claim Rejections - 35 USC § 103
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 – 13 are rejected under 35 U.S.C. 103 as being unpatentable over Teranishi et al. (US 10,350,310) as evidenced by Kurahasi et al. (J Biomed Optics, 2016) in view of Onai et al. (US 2009/0325978).
Teranishi et al. discloses novel indocyanine green (ICG) compounds and diagnostic compositions of such compounds that solve the problems of conventional ICG such as solubility in water or physiological saline (whole document, e.g., abstract). The compositions are cyclic sugar chain cyclodextrin-bonded indocyanine compounds that is a green pigment and emits near-infrared (NIR) light (col 1, ln 30 - 45). The sulfonyl group means ICG is water soluble but adsorbs to lipids (col 2, ln 56 – 60) amongst others issues with ICG. These problems are solved by the present invention (col 3, ln 21 – 30). The compound across cols 41 and 42 are pudexacianinium (see Figure 1B of Kurahasi et al. of the structure of TK-1, also known as pudexacianinium; see also ¶ [0002] of the PGPub of the instant application). After purification, the non-inclusion type cyclodextrin-bonded ICG compound can be obtained in the solid state after removal of the medium by lyophilization (col 27, ln 49 – col 28, ln 14, lines 10 – 14 in particular).
The inclusion of a buffer and excipient in a solid dosage form are not disclosed.
Onai et al. discloses a stable lyophilized preparation with excellent stability over time and solubility when reconstituted containing (8E,12E,14E)-7-((4-cycloheptylpiperazin-1-yl)carbonyl)oxy-3,6,16,21-tetrahydroxy-6,10,12,16,20-pentamethyl-18,19-epoxytricosa-8,12,14-trien-11-olide or pharmaceutically acceptable salt thereof, a pH-regulator to adjust the pH of the preparation to between 5and 8 and at least one excipient selected from sugars and sugar alcohols (whole document, e.g., abstract). The pH regulator adjusts the pH to between 5 and 8, more preferably between 5.8 and 7.2 and a more preferable pH adjuster is citric acid and salts thereof such as sodium citrate (¶ [0023]). Aqueous solutions of sodium hydroxide (NaOH), hydrochloric acid (HCl) or the like can be used to adjust the pH (¶ [0023]). There are no particular restrictions on the amount of pH regulator added but ranges such as 0.1 – 300 and 0.3 – 50 parts by weight are disclosed (¶ [0024]). The sugar or sugar alcohol is preferably sucrose (¶ [0027]). The sugar or sugar alcohol excipient is present in an amount of at least 40% by weight (¶ [0028]). Additional ingredients such as stabilizers, such as cyclodextrins, can also be contained in the lyophilized formulation (¶ [0030]). The preparation can be made by a process in which the therapeutic acid, pH regulator, sugar or sugar alcohol and any additional ingredients if needed are dissolved in water or a suitable aqueous solvent; the solution is filter sterilized; aliquoted into vials and subjected to ordinary freeze drying (lyophilization) to give a solid powder (¶ [0040]). The drying time and temperature can be adjusted to control the water content of the lyophilized preparation and it is more preferable the water content is no more than 1.5% although larger ranges such as no more than 2.0% are also disclosed (¶ [0038]).
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to incorporate a buffer such as citrate and excipients such as the sugar sucrose in a lyophilized formulation of pudexacianinium. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because Teranishi et al. generally disclosed solid lyophilized preparations of TK-1/ pudexacianinium but provides no information as to how to prepare such formulations and ingredients other than the therapeutic agent for such formulations. Onai et al. provides explicit guidance in addition to the knowledge of one of ordinary skill in the art as to the materials and processes for the preparation of lyophilized formulations. pH adjusters such a citrate and sugars such as sucrose can be added to aid in the lyophilization process. The use of chloride containing materials such as HCl to adjust the pH solution will result in the presence of a chloride salt. When sodium containing materials such as sodium citrate and/or sodium hydroxide are also used, the solid material will contain sodium. The amount of a specific ingredient in a composition is clearly a result effective parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ and reasonably would expect success. It would have been customary for an artisan of ordinary skill to determine the optimal amount of each ingredient to add in order to best achieve the desired results and the particular therapeutic agent. There is no evidence of record as to the criticality of the claimed amounts of the various ingredients in either a solid form or aqueous solution, either prior to lyophilization or should the solid formulation be reconstituted with water prior to use. The method of instant claim 12 is disclosed by Onai et al.
As to claim 9, this appears to reflect the stability of the formulation over time that might be influenced by factors such as water content, buffer and excipients that are present and the structural limitations of the claims are rendered obvious as discussed in greater detail above. It is noted that In re Best (195 USPQ 430) and In re Fitzgerald (205 USPQ 594) discuss the support of rejections wherein the prior art discloses subject matter which there is reason to believe inherently includes functions that are newly cited or is identical to a product instantly claimed. In such a situation the burden is shifted to the applicants to "prove that subject matter shown to be in the prior art does not possess characteristic relied on" (205 USPQ 594, second column, first full paragraph). There is no evidence of record as to the criticality of the claimed structural components selected such that such levels of related substances would not be present in the materials rendered obvious by the combination of Teranishi et al. and Onai et al.
Claim(s) 8 and 11 are rejected under 35 U.S.C. 103 as being unpatentable over Teranishi et al., Kurahasi et al. and Onai et al. as applied to claims 1 – 13 above, and further in view of Deluca et al. (J Pharm Sci, 1965).
Teranishi et al., Kurahasi et al. and Onai et al. are discussed above. In addition to the teachings of Teranishi et al. discussed above, the aqueous solutions of TK-1/pudexacianinium were injected (e.g., col 51, ln 30 - 32).
The explicit presence of sodium chloride in the lyophilized preparation is not disclosed.
Deluca et al. discloses that inorganic electrolytes are routinely used for tonicity adjustment in lyophilized injectable dosage forms but can affect the freeze-drying cycles (p 1411, col 1, ¶ 1). Halogen salts of sodium and potassium, including sodium chloride, and the chlorides of lithium and cesium were studied (p 1411, col 1, ¶ 2 and figures 1 – 4). The drug and the selected electrolyte can influence the conditions necessary for lyophilization (p 1414, col 2, ¶¶ 2 and 3).
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to include an electrolyte such as NaCl in the lyophilized dosage form to adjust the tonicity of the TK-1/pudexacianinium containing formulation when reconstituted for injection into a subject. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because Deluca et al. discloses that NaCl can be used for tonicity adjustment and is compatible with lyophilization procedures and will also result in the presence of the chloride salt of TK-1 in the preparation. The amount of a specific ingredient in a composition is clearly a result effective parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ and reasonably would expect success. It would have been customary for an artisan of ordinary skill to determine the optimal amount of each ingredient to add in order to best achieve the desired results. There is no evidence of record as to unexpected results from the particular salt used such as NaCl in the claimed preparations of pudexacianinium.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Nissa M Westerberg whose telephone number is (571)270-3532. The examiner can normally be reached M - F 8 am - 4 pm.
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/Nissa M Westerberg/Primary Examiner, Art Unit 1618
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