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 .
Election/Restrictions
Claims 9-13 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on March 16, 2026.
Claims 1-8 are examined on the merits.
Claim Rejections - 35 USC § 112
§ 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-8 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement.
The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
Evaluating enablement requires determining whether any undue experimentation is necessary for a skilled artisan to determine how to make and/or use the claimed invention. Factors to be considered in determining whether any necessary experimentation is “undue” include, but are not limited to: a) the breath of the claims; b) the nature of the invention; c) the state of the prior art, the level of one of ordinary skill; d) the level of predictability in the art; e) the amount of direction provided by the inventor; f) the existence of working examples; and g) the quantity of experimentation needed to make or use the invention based on the content of the disclosure. See In re Wands, 858 F.2d 731, 737, 8 U.S.P.Q. 2d 1400, 1404 (Fed. Cir. 1988).
The breath of the claim
Claim 1 is directed to a dispersion composition comprising:
a dispersion medium; and particles comprising a target substance,
wherein the dispersion composition comprises at least one type of surfactant having a critical micelle concentration or more,
the dispersion composition does not comprise a solubilizer,
the target substance is cyclosporin A,
if the dispersion composition comprises at least one type of surfactant, the S-parameter of Equation 3 calculated by Equation 1 and Equation 2 satisfies S-parameter >1, and
if the dispersion composition comprises at least two types of surfactants having a critical micelle concentration or more, Ssurf(i) obtained by Equation 4 below is calculated for each type of surfactant, and then the Ssurf value is obtained as the sum of these by Equation 5 below and the S-parameter of Equation 3 obtained by applying the calculated Ssurf value to Equation 1 above satisfies S-parameter >1:
S micelle =S w +S surf <Equation 1>
wherein Sw is the concentration corresponding to the saturation solubility of the target substance in the dispersion medium, and Ssurf is calculated by Equation 2 below,
S surf =k(C surf−CMC) <Equation 2>
wherein k is the molar solubilization capacity defined as the number of moles of the target substance that can be dispersed in the dispersion medium by one type of surfactant having the critical micelle concentration of 1 mole or more, and Csurf is the molar concentration of the surfactant component in the composition, and CMC is the critical micelle molar concentration of the surfactant in the composition,
S-parameter=S tot /S micelle <Equation 3>
wherein Stot is the total molar content of the target substance contained in the dispersion composition,
S surf(i) =k surf(i)(C surf(i)−CMCsurf(i)) <Equation 4>
wherein ksurf(i) is a molar solubilization capacity defined as the number of moles of the target substance that can be dispersed in the dispersion medium by any one type of the surfactant components having the critical micelle concentration of 1 mole or more, Csurf(i) is the concentration of any one of the surfactant components having the critical micelle concentration or more, and CMCsurf(i) is the critical micelle concentration in the dispersion medium of any one type of the surfactant components having the critical micelle concentration or more, and
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wherein m is the total number of types of surfactant components having the critical micelle concentration or more.
Claim 1 is directed to a dispersion composition comprising one or more surfactant and particles comprising cyclosporin A, without a solubilizer; the claim requires the composition to meet the solubility parameter and molar solubilization capacity in mathematic equations. There is no limitation as to the type of the dispersion medium, the type or number of the surfactants; there is no requirement cyclosporin A has to be in a specific form or in dispersed state. Furthermore, as the claim language in defining the equation is highly ambiguous, determining whether a composition would be within the scope of the composition would impose undue burden on a person or ordinary skill in the art. See below, rejections under 35 U.S.C. 112 (b).
The nature of the invention
The claimed invention is cyclosporin A preparation with improved solubility with minimum contents of surfactant and no oils (solubilizer), produced in a flow-through porous media process.
The state of the prior art
Currently, Cyclosporin A formulations on the market (e.g., Restatis, Cequa and Ikervis) for treating dry eye syndrome rely heavily on oils and surfactants. See published pec. [0010-0012]. Applicant also states in [0062], “[t]he S-parameter for the dispersion composition prepared by incorporating the surfactant by the existing micelle solubilization technology cannot exceed 1.”
The level of one of ordinary skill:
The level of a person of ordinary skill in the art would be very high in this case and would need an advanced education in pharmaceutical science and physical chemistry and field experience in drug formulation.
The level of predictability in the art:
Pharmaceutical and chemical art are highly unpredictable. As indicated above, applicant also admits that it is highly improbable to make a dispersion which meets the S-parameter greater than 1.
The amount of direction provided by the inventor/ The existence of working examples:
In Examples 1-1 to 1-4, applicant describes the process of preparing cyclosporin A powder: Dissolved drug is passed through a densely packed mesoporous silica bed under specific conditions (e.g., flow rate, retention time, etc) and the solvent is removed to yield cyclosporin A powder with different solubility characteristics.
The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
Although the specification discloses a method of making the claimed product by a conventional chemical process, the claim defines the product with parameters and results with mathematic equations for the entire class of surfactants and dispersion mediums in an undefined environment conditions, which would require one of ordinary skill in the art to conduct extensive experiments to test if any dispersion medium and surfactant(s) comprising cyclosporin A would fit in the equation. As the specification shows a limited example of one embodiment of a method of making the dispersion which would meet the parameter and solubility requirement, the burden is on others to guess and create ways to modify the solubility characteristics of the drug and test if their product would meet the parameters in the claim. Moreover, the person of ordinary skill in the art would not even be able to use the equations to conduct such tests due to the ambiguity of the scope of the claim. No skilled artisan would be able to make and use the claimed product without a prohibitive degree of undue experimentations.
§ 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.
Claims 1-8 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 recites, “wherein the dispersion composition comprises at least one type of surfactant having a critical micelle concentration or more”. As a critical micelle concentration (“CMC”) is a property of a surfactant, it is not clear what applicant means by “having a critical micelle concentration or more”.
Claim 1 also goes on to recite, “if the dispersion composition comprises at least one type surfactant”. This conditional clause renders the claim vague and indefinite as the above wherein clause specifically requires at least one type of surfactant. It is not clear if the conditional clause implies the at least one surfactant can be optional or required.
Claim 1 also recites saturation solubility “Sw” without specifying the physical conditions such as the temperature, pressure and solvent. Even applicant admits in the specification that “the saturation solubility of a specific target substance in a specific dispersion medium is determined as a unique value depending on conditions comprising the type, composition, phase and content of the target substance, the type and composition of the dispersion medium, and temperature and pressure.” See p. spec. 16. Similarly, the CMC of a surfactant would also vary depending on the temperature, the pH or the contents of the water. As at least the Sw value and the CMC are variable, the calculation according to the equation will yield different results depending on the conditions; the metes and bounds of the scope of the claim cannot be determined.
Furthermore, the value “k” in Equation 2 is not a defined, static number. The claim recites “k is the molar solubilization capacity defined as the number of moles of the target substance that can be dispersed in the dispersion medium by one type of surfactant having the critical micelle concentration of 1 mole or more”. (emphasis mine). The k value may depend on a specific surfactant used, but the scope of the claim is open to include more than one surfactant. The metes and bounds of the scope of the claimed invention cannot be determined.
Claim 1 requires a dispersion composition, but does not specifically require the particles comprising the target substance are dispersed in the composition. Moreover, although claim 1 recites, “Stot is defined as “the total molar content of the target substance contained in the dispersion composition”, the Stot merely refers to the amount of the drug ‘contained’ in the composition rather than ‘dispersed’ therein. Claim 1 is vague and indefinite as it is not clear what applicant means to include in the scope of the term “dispersion” and the structure of the composition is not unclear.
At least for above reasons, claim 1 is vague and indefinite, and does not particularly point out what the present invention is. One of ordinary skill in the art or other inventors would not be able to determine the scope of this invention. Lack of prior art rejections in this Office action is not an indication the present invention is free of prior art.
The remaining claims are rejected for depending on the indefinite base claim.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GINA CHIEUN YU JUSTICE whose telephone number is (571)272-8605. The examiner can normally be reached M-F 9:00 AM - 5 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, BETHANY BARHAM can be reached at 571-272-6175. 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GINA JUSTICE whose telephone number is (571)272-8605. The examiner can normally be reached M-F 9:00 AM - 5 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, BETHANY BARHAM can be reached at 571-272-6175. 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.
/GINA C JUSTICE/Primary Examiner, Art Unit 1617
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