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 102(A)(1)
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 8-10 are rejected under 35 U.S.C. 102(A)(1) as being anticipated by Zhu et al. (Experimental Eye Research, Vol. 199, 2020, 108180; See ISR).
Zhu teaches a composition for treating ocular inflammation in mouse models of both endotoxin induced uveitis (EIU) and autoimmune uveitis (EAU) with the cell permeable peptide TAT-24, which is a cell penetrating peptide inhibitor of p55PIK (Abstract). This reference teaches that the P55PIK inhibiting peptide, was formulated in eye-drops of vehicle with 0.1% TAT-N24, 0.5% TAT-N24, 0.9% TAT-N24 and 0.1% Dex, which were topically administered 4 times per day for 2 days before LPS injection in the EIU group, and changed to every 2 h for 24 h subsequently after EIU induction (p. 2, Col. 2, section 2.3).
This meets the limitations of claim 8 by teaching a therapeutic drug comprising a p55PIK inhibitor. As to the limitation “for dry eye,” this is an intended use of the composition, which does not impart any structural differences between the prior art composition and the instantly claimed composition. MPEP 2112.01 states: “Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). "When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). Therefore, the prima facie case can be rebutted by evidence showing that the prior art products do not necessarily possess the characteristics of the claimed product. In re Best, 562 F.2d at 1255, 195 USPQ at 433. See also Titanium Metals Corp. v. Banner, 778 F.2d 775, 227 USPQ 773 (Fed. Cir. 1985) (Claims were directed to a titanium alloy containing 0.2-0.4% Mo and 0.6-0.9% Ni having corrosion resistance. A Russian article disclosed a titanium alloy containing 0.25% Mo and 0.75% Ni but was silent as to corrosion resistance. The Federal Circuit held that the claim was anticipated because the percentages of Mo and Ni were squarely within the claimed ranges. The court went on to say that it was immaterial what properties the alloys had or who discovered the properties because the composition is the same and thus must necessarily exhibit the properties.).”
Furthermore MPEP 2112.01 states: “Statements in the preamble reciting the purpose or intended use of the claimed invention must be evaluated to determine whether or not the recited purpose or intended use results in a structural difference (or, in the case of process claims, manipulative difference) between the claimed invention and the prior art. If so, the recitation serves to limit the claim. See, e.g., In re Otto, 312 F.2d 937, 938, 136 USPQ 458, 459 (CCPA 1963) (The claims were directed to a core member for hair curlers and a process of making a core member for hair curlers. The court held that the intended use of hair curling was of no significance to the structure and process of making.); In re Sinex, 309 F.2d 488, 492, 135. USPQ 302, 305 (CCPA 1962) (statement of intended use in an apparatus claim did not distinguish over the prior art apparatus).”
As such, the claim use of the known product is inherent to the composition itself, as the only claimed difference is the composition’s ability to be use in dry eye treatment.
As such, the claimed composition itself was recited by the prior art, which teaches the same P55PIK inhibitor of claim 8. Additionally, Zhu teaches that the concentration of claim 9, which is .1% to .9% w/v TAT-N24 by weight, as discussed above. Claim 10 is met because the therapeutic drug is stated to be a cell-penetrating peptide, which is within the definition of the specification (see para. 10-11), and TAT-N24 is TAT (transactivator) protein coupled to the 24 residue P55PIK inhibitor (See p. 1, definitions; See p. 2, Col. 1, para. 1-2).
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.
Claim(s) 1-4 and 7-10 are rejected under 35 U.S.C. 103 as being unpatentable over Zhu et al., as applied to claims 8-10 above, in view of Baudouin et al. (Acta Ophthalmologica, 2018, 96: 111–119).
The teachings of Zhu regarding the p55PIK inhibitor peptide composition have been described supra.
Zhu further teaches that their results showed TAT-N24 alleviated clinical signs, decreased inflammatory cell infiltration and the expression of inflammatory cytokines in both EIU and EAU models of uveitis (abstract). Additionally, Zhu teaches that protein levels of tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) in aqueous humor and mRNA and protein levels of NF-κB p65 in the ICB significantly decreased in EIU model and that in EAU model, TAT-N24 application induced a significant decrease of IFN-gamma (IFN-γ) and interleukin-17 (IL-17) in the retina (Abstract). This reference concludes that p55PIK signaling (TAT-N24) suppressed intraocular inflammation and that the anti-inflammatory effects of TAT-N24 were mediated by suppressing inflammatory cytokines, which establishes that TAT-N24 could be potentially a novel class of agent for the treatment of ocular inflammation (p. 7, Col. 2, para. 2).
The difference between the prior art and the instant claims is that the prior art does not teach specifically treating dry eye with the P55PIK inhibitor.
Baudouin teaches that it is well recognized that the pathophysiology of chronic dry eye disease can include a cycle of inflammation involving both innate and adaptive immune responses (abstract). This reference further teaches that one of the current therapeutic strategies focuses on breaking the inflammatory cycle perpetuating the ocular surface disease, and preclinical/clinical research has led to the development of promising anti‐inflammatory compounds, such as cyclosporine, corticosteroids, doxycycline and essential fatty acids, through their anti‐inflammatory properties, which have shown encouraging results for treating dry eye disease (abstract). Baudouin also teaches that increases in tear film osmolarity, triggered by dysfunctional tear secretion (aqueous tear-deficient dry eye) and/or excessive water evaporation with normal lacrimal secretory function (evaporative dry eye) may lead to hyperosmotic, desiccating and mechanical/shear stresses (due to loss of hydration/lubrication) that initiates inflammatory events in dry eye disease (p. 112, Col. 2, para. 2).
It would have been obvious, based on the teachings of Baudouin, to have taken the P55PIK inhibitor of Zhu and used it to treat dry eye disease and associated inflammation are well known to be a part a chronic inflammatory cycle (abstract). One would be motivated to do so because Baudouin teaches that anti-inflammatory eye therapeutic compositions have been successful in treating dry eye disease by breaking the inflammation cycle, and Zhu teaches that P55PIK inhibitors are effective in treating ocular inflammation. As such, there is a reasonable expectation of success, that that the method of Zhu can be used to treat dry dye disease because Boudin teaches that these two conditions often overlap and that treating ocular inflammation can also treat dry eye diseases by breaking the dry eye disease/inflammation cycle.
This meets the limitations of claims 1-2 by rendering it obvious to treat dry eye disease with the ani-inflammatory P55PIK inhibitor composition. Claims 3 and 4 are met because Zhu teaches TAT-N24, which is a 24 residue P55PIK peptide inhibitor, and TAT is a cell penetrating peptide carrier, as discussed above. Claim 7 is met because Baudouin also teaches that dry eye disease and inflammation go hand in hand, as evaporative and aqueous tear deficient dry eye diseases lead to ocular inflammation in the cycle (p. 112, Col. 2; p. 111, Introduction).
Claim(s) 1-10 are rejected under 35 U.S.C. 103 as being unpatentable over Zhu et al. (See ISR) in view of Baudouin et al. (Acta Ophthalmologica, 2018, 96: 111–119), as applied to claims 1-4 and 7-10 above, and in further view of Xia et al. (CN1100882228A; See ISR)
The teachings of Zhu and Baudouin have been discussed supra.
The difference between the prior art and the instant claims is that the prior art does not teach a method of using a peptide having SEQ ID NO: 7.
Xia teaches methods of making epivotide, which is used for signal transmission of specifically blocking p55PIK, which causes the cell cycle involved in inflammation and production and secretion of multiple kinds of inflammation factors to be inhibited, which can effectively block the inflammatory process (See beneficial effects, No. 1 of translation). This reference further teaches that the epivotide amino acid sequence is as follows: NH2-Tyr-Gly-Arg-Lys-Lys-Arg-Arg-Gln-Arg-Arg-Arg-Met-Met-Pro-Tyr-Ser-Thr-Glu-Leu-Ile-Phe-Tyr-Ile-Glu-Met-Asp-Pro-COOH (Claim 5).
It would have been obvious to one of ordinary skill in the art at the filing date of the invention to have taken the method of treating dry eye with a P55PIK inhibitor taught by Zhu and Baudouin and used the epivotide peptide taught be Xia because Xia teaches that epivotide is a P55PIK inhibitor. One would be motivated to do so because Zhu teaches that P55PIK inhibitors are effective in treating ocular inflammation, Baudouin provides motivation to treat dry eye with P55PIK inhibitors, and Xia teaches that epivotide is an anti-inflammatory P55PIK inhibitor. As such, there is a reasonable expectation of success that dry eye/inflammation cycles, as discussed in Baudouin, can be effectively treated with the composition of Xia.
This meets the limitations of claim 5 because epivotide comprises SEQ ID NO 7: Met-Met-Pro-Tyr-Ser-Thr-Glu-Leu-Ile-Phe-Tyr-Ile-Glu-Met-Asp-Pro, and the N-terminus of epivotide is TAT: NH2-Tyr-Gly-Arg-Lys-Lys-Arg-Arg-Gln-Arg-Arg-Arg. As such, epivotide is SEQ ID NO: 7, linked to a cell penetrating peptide through a peptide bond, rendering obvious claim 6.
Conclusion
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/JEANETTE M LIEB/Primary Examiner, Art Unit 1654