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 Status
Claims 24-26, 29-30, and 43 are rejected.
Claims 32-39 and 41 are withdrawn.
No claims are allowable.
New Claim Rejections - 35 USC § 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.
Claim 24 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
This is a new matter rejection.
Claim 24 has been amended to recite wherein the dextran-rich droplets comprise water soluble melanin. The claim fails to comply with the written description requirement since such limitation is not described in the specification. As noted in paragraph [0034] of the instant specification, tyrosinase sequestration by the Dex-rich droplets allows for confined local reactivity, resulting in formation of soluble melanin in the compartments. The current system utilizes aqueous compartments to generate a water-soluble melanin. Thus, it appears that the dextran-rich droplets do not necessarily comprise a water-soluble melanin until it is generated by the instantly claimed system.
New 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 24 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.
Newly amended claim 24 recites the limitations “polyethylene glycol (PEG)-rich continuous phase” and “dextran rich droplet of PEG/dextran ATPS.” It is unclear how much PEG is necessary for a continuous phase to be considered PEG rich and it is unclear how much dextran is necessary for a droplet of PEG/dextran to be considered dextran rich.
Response to Applicant’s Arguments
Applicant argues that the limitations do not need to be quantitative, but rather to indicate that the PEG mostly partitions into the continuous phase and the dextran is mostly found in the dispersed droplets.
Applicant’s argument has been fully considered but found not to be persuasive. When a subjective term is used in the claim, some objective standard must be provided in order to allow the public to determine the scope of the claim. A claim term that requires the exercise of subjective judgment without restriction may render the claim indefinite. See MPEP 2173.05(b)(IV). The applicant has not amended the claim to remove the subjective term, or by provided evidence that the metes and bounds of the term can be ascertained by one of ordinary skill in the art when reading the disclosure. Further, the term “mostly” as applied in the Applicant’s argument is also subjective, and as such, does not clarify or further define the scope of the subjective terms in the claim. Thus, the rejection is modified and maintained.
Maintained 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.
1. Claims 24, 29-30, and 43 are rejected under 35 U.S.C. 103 as being unpatentable over Shum et al., (US 2015/0157569 A1, June 11, 2015) (hereinafter Shum) in view of Herlihy (US 4,515,773 A, May 07, 2015) (hereinafter Herlihy).
Shum discloses methods for preparing all-aqueous emulsions that include mixing, combining, or contacting a first electrically charged phase containing a first solute (e.g., dispersed phase) with at least a second phase containing a second solute (e.g., continuous phase). The solutes are incompatible with each other. The electrostatic forces between the two phases induce the formation of droplets of a dispersed phase in a continuous phase ([0011]). The emulsions can be used for a variety of applications, such as drug delivery (e.g., small molecules, biomolecules, cells, etc.) and encapsulation of actives for cosmetics ([0013]). “All-aqueous emulsion” and “Aqueous two-phase systems (ATPSs)” are used interchangeably ([0016]). One or more phases can contain one or more therapeutic agents. Further, the solution that forms the dispersed phase may contain one or more therapeutic agents which are encapsulated within the droplets upon formation of the emulsion ([0029]). A core-shell structured emulsion can also be generated comprising a shell (e.g., PEG-rich continuous phase) and core (e.g., dextran-rich phase) (i.e., wherein the polymer of the polymer-based droplet is PEG and dextran) (i.e., the core meeting the limitation of a dextran-rich droplet) ([0056]). Fig. 1 shows in panel c a microscopic image of an all-aqueous emulsion with a core-shell structure ([0014]). The emulsions can be combined with one or more carriers ([0071]). In Example 1 a dispersed phase of 8 wt % PEG (Mw=8,000) solution charged with a high DC voltage is sprayed into its immiscible aqueous phase of 15 wt % dextran (Mw=500,000) solution through air. The diameter of the produced droplets is significantly reduced from 810 μm to 120 μm by increasing the applied electric field ([0081]).
Shum differs from the instant claims insofar as not disclosing wherein the droplets comprise an unprotected tyrosine and a tyrosinase.
However, Herlihy teaches that though tanning of the human skin is motivated largely by cosmetic desires, it is also recognized that tanning, when done without detrimental burning, can have a protective effect on the skin (col 1, lines 35-38). Herlihy discloses a non-mutagenic, non-allergenic tanning composition which can be applied to the human epidermis to achieve a desired cosmetic effect and protect the skin from harmful sun rays (i.e., therapeutic effect) through the use of the enzyme tyrosinase to catalyze the formation of melanin-like dyes on the human skin, initiated by mixing tyrosinase and a suitable dye precursor directly on the skin (col 1, lines 52-63). The skin tanning composition which imparts color to the human epidermis (i.e., cosmetic) comprises a cosmetic base in the form of a lotion, a cream or an ointment, an effective amount of the dye precursor such as tyrosine, and an effective amount of tyrosinase (Claim 1). These ingredients, when reacted together on the skin, result in the formation of melanin-like dyes which tan the skin (Abstract). The dye precursor and tyrosinase are in the same component but they are physically or chemically prevented from reacting. For example, tyrosinase can be sequestered by microencapsulation (col 1, lines 64-67).
As discussed above, Shum discloses wherein the composition comprises actives for cosmetics and therapeutic agents. Accordingly, it would have been prima facie obvious to one of ordinary skill in the art to have formulated the composition of Shum to comprise tyrosine (i.e., an unprotected tyrosine) and tyrosinase since the combination forms a therapeutic active agent for protecting the skin as taught by Herlihy.
Response to Applicant’s Arguments
Applicant argues that the charged polymers of Shum are easily disrupted and can disassemble upon environmental changes or upon biocatalytic reactions, such as oxidation (e.g., of tyrosine into melanin), leading to undesired heterogenous reaction mixture in which melanin is not spatially confined inside compartments.
Applicant’s argument has been fully considered but found not to be persuasive. Applicant has not provided any objective evidence supporting Applicant’s assertion. Therefore, since Applicant’s argument is merely speculative, Applicant’s argument is unpersuasive.
Applicant argues that the charged polymers limit the partitioning of the tyrosinase enzyme and the tyrosine substrate in the ATPS system, since they provide a barrier and may electrostatically repel the tyrosinase, therefore, no spatial control over melanin synthesis is expected in the system described by Shum and melanin cannot be predictably accumulated in the dextran-rich droplets.
Applicant’s argument has been fully considered but found not to be persuasive. Applicant has not provided any objective evidence supporting Applicant’s assertion. Therefore, since Applicant’s argument is merely speculative, Applicant’s argument is unpersuasive.
Additionally, the claims as currently recited do not require melanin in the dextran-rich droplets. As recited in instant claim 24, the presence of melanin is optional.
Applicant argues that Shum does not mention or suggest partitioning of tyrosine and tyrosinase into the droplets.
Applicant’s argument has been fully considered but found not to be persuasive. As this is a 103 obviousness rejection, no one piece of prior art is required to teach each and every claim limitation. As discussed above, Shum teaches a dextran dispersed phase containing one or more therapeutic agents which are encapsulated within the droplets (i.e., partitioned) upon formation of an emulsion. Herlihy teaches that the combination of tyrosine (i.e., an unprotected tyrosine) and tyrosinase forms a therapeutic active agent for protecting the skin. Thus, the combined teachings of Shum and Herlihy suggest that the therapeutic agents tyrosine (i.e., an unprotected tyrosine) and tyrosinase are encapsulated within the droplets (i.e., partitioned) upon formation of an emulsion.
Applicant argues that Shum does not suggest that soluble melanin may be formed in the droplets or provide any basis for a reasonable expectation that the claimed melanin production reaction would be successful if carried out in an ATPS.
Applicant’s argument has been fully considered but found not to be persuasive. The claims as currently recited do not require melanin to be formed in the droplets or a melanin production reaction. As recited in instant claim 24, the presence of melanin is optional and the production of melanin is not required in independent claim 24 or subsequent dependent claims.
Applicant argues that Herlihy does not mention ATPS, droplets, or compartmentalization of the tyrosine and tyrosinase, and does not teach or suggest that the tyrosine and tyrosinase would correctly partition.
Applicant’s argument has been fully considered but found not to be persuasive for reasons discussed above. As this is a 103 obviousness rejection, no one piece of prior art is required to teach each and every claim limitation. As discussed above, Shum teaches a dextran dispersed phase containing one or more therapeutic agents which are encapsulated within the droplets (i.e., partitioned) upon formation of an emulsion. Herlihy teaches that the combination of tyrosine (i.e., an unprotected tyrosine) and tyrosinase forms a therapeutic active agent for protecting the skin. Thus, the combined teachings of Shum and Herlihy suggest that the therapeutic agents tyrosine (i.e., an unprotected tyrosine) and tyrosinase are encapsulated within the droplets (i.e., partitioned) upon formation of an emulsion.
Applicant argues that Herlihy does not mention that the enzymatic reaction catalyzed by the tyrosinase to create a melanin pigment is even suitable for being carried out in an ATPS.
Applicant’s argument has been fully considered but found not to be persuasive. The claims as currently recited do not require a reaction to be carried out in an ATPS. Independent claim 24 requires dextran-rich droplets comprising an unprotected tyrosine and tyrosinase, which is taught by Shum and Herlihy as discussed above.
Applicant argues that neither Shum or Herlihy provides motivation or any reason to replace the simple method of Herlihy with the more complex ATPS system.
Applicant’s argument has been fully considered but found not to be persuasive. The office action does not assert that the method of Herlihy should be replaced with the more complex ATPS system. As discussed above, Shum discloses wherein the composition comprises actives for cosmetics and therapeutic agents and Herlihy teaches that the combination of tyrosine (i.e., an unprotected tyrosine) and tyrosinase forms a therapeutic active agent for protecting the skin. Accordingly, tyrosine (i.e., an unprotected tyrosine) and tyrosinase are known and effective therapeutic agents used in cosmetics and thus one of ordinary skill in the art would have been motivated to select these agents as the actives of Shum.
Applicant argues that neither Shum nor Herlihy provides an indication that the ATPS system is even suitable for the tyrosinase-tyrosine system for producing melanin.
Applicant’s argument has been fully considered but found not to be persuasive. The claims as currently written do not recite a tyrosinase-tyrosine system for producing melanin.
Applicant argues that the present invention was surprisingly able to generate water- soluble melanin, since generation of the melanin inside the droplets prohibits it from aggregating.
Applicant’s argument has been fully considered but found not to be persuasive. The arguments of counsel cannot take the place of evidence in the record. See MPEP 716.01(c). Applicant has not provided any objective evidence supporting Applicant’s assertion that the generated melanin is water-soluble. As noted in paragraph [00095] of the instant specification, the examples provided indicate the presence of a melanin-like material. While paragraph [00034] discloses that the instantly claimed system generates a water-soluble melanin, evidence of such generation is not found in the examples of the instant specification or an affidavit/declaration. Further, prevention of aggregation in water does not automatically equate to water solubility. Therefore, since Applicant’s argument is merely speculative, Applicant’s argument is unpersuasive.
2. Claims 25 and 26 are rejected under 35 U.S.C. 103 as being unpatentable over Shum et al., (US 2015/0157569 A1, June 11, 2015) (hereinafter Shum) in view of Herlihy (US 4,515,773 A, May 07, 2015) (hereinafter Herlihy) and further in view of Mayer et al., (Biologically Active Molecules with a “Light Switch”, July 20, 2006) (hereinafter Mayer).
As discussed above, Shum and Herlihy make obvious the limitations of claim 24 but do not teach wherein the tyrosine comprises a cleavable protecting group on a side chain which is photocleavable or chemically cleavable, and wherein the protected tyrosine is ortho-nitrobenzyl tyrosine (ONB-Y).
However, Mayer discloses “small molecules”, proteins, and nucleic acids which can either be irreversibly activated with light (these compounds are referred to as “caged compounds”) or reversibly switched between an active and an inactive state (Abstract). “Caging” involves the modification of a biologically active substance with a photo-labile “protecting” group to make it temporarily inactive (page 4901, Introduction). Before the term “caging” was coined α-chymotrypsin (CT) had already been temporarily deactivated by cis-cinnamoylation. Only upon isomerization to the trans-form is the cinnamoyl group cleaved, regenerating the active enzyme which can then, for example, cleave a tyrosine ester. The resulting tyrosine can then be converted into the pigment melanin by tyrosinase (page 4902, Scheme 2). The ortho-nitrobenzyl group (ONB) with all its derivatives is the most commonly used caging group (page 4903, Caging Groups and Reversible Photoswitches). An ONB group is incorporated by derivatizing a tyrosine residue 242 (Y242), resulting in a cage at the critical position Y242 to control the activity of the receptor by light (page 4909, 4.3. Caged Receptors and Receptor Agonists). The o-nitrobenzyl linker is photocleavable (i.e., a cleavable protecting group on a side chain of the tyrosine is photocleavable) (page 4917, third paragraph).
Herlihy discloses compositions comprising tyrosine and tyrosinase that should be physically or chemically prevented from reacting. Accordingly, it would have been prima facie obvious to one of ordinary skill in the art to have incorporated an ortho-nitrobenzyl group (ONB) onto the tyrosine of Herlihy, resulting in a tyrosine substrate with a cleavable protecting group on a side chain (protected tyrosine), to make it temporarily inactive as taught by Mayer, thus preventing it from reacting.
Response to Applicant’s Arguments
Applicant argues that Mayer's teaching would likely lead a person skilled in the art to cage the tyrosinase enzyme, rather than the tyrosine substrate.
Applicant’s argument has been fully considered but found not to be persuasive. As discussed above, Mayer teaches that an ONB group is incorporated by derivatizing a tyrosine residue (i.e., tyrosine substrate) 242 (Y242), resulting in a cage at the critical position Y242 to control the activity of the receptor by light. Only once the ONB group is photocleaved can the caged tyrosine be converted into the pigment melanin by tyrosinase (i.e., tyrosinase enzyme). Thus, it is clear that it is the tyrosine residue itself that receives the ONB group since it is the tyrosine residue (i.e., tyrosine substrate) that is caged by the ONB group and the tyrosinase (i.e., tyrosinase enzyme) only acts upon the tyrosine once the ONB group is no longer caging the tyrosine.
Applicant argues that a person skilled in the art would not be able to predict whether tyrosine blocked by the protecting group would properly partition in dextran-rich droplets of an ATPS system because addition of an ONB group could affect appropriate partitioning of the tyrosine substrate.
Applicant’s argument has been fully considered but found not to be persuasive. Applicant has not provided any objective evidence supporting Applicant’s assertion. Therefore, since Applicant’s argument is merely speculative, Applicant’s argument is unpersuasive.
Conclusion
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.
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/S.J.K./Examiner, Art Unit 1614
/TRACY LIU/Primary Examiner, Art Unit 1614