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 Claims
Claims 1, 11, 15, 20, 24, 28, 52, 54, 96, 125-127, 140, 148, 154, and 187 are pending.
Claims 125-127, 140, 148, 154, and 187 are withdrawn from consideration as directed to non-elected inventions.
Claims 1, 11, 15, 20, 24, 28, 52, 54, and 96 are presented for examination and rejected as set forth in greater detail below.
Claim Interpretation
Applicants claims are directed to compositions which combine niclosamide, lysozyme, and an excipient which is either a sugar, sugar derivative, or compound with a hydrophobic and PEG or propylene glycol component. Dependent Claims 11, 15, and 20 require the inclusion of various excipients. Claims 24 and 28 define concentrations of niclosamide and protein present in the composition. Claims 52, 54, and 96 specify that the composition is to be formulated for delivery via inhalation, in an inhaler, or for nasal administration.
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.
Claims 1, 11, 15, 20, 24, 28, 52, 54, and 96 are rejected under 35 U.S.C. 103 as being unpatentable over Krieger (U.S. PGPub. 2002/0035061), in view of Brown (WO2018/141063), and Serra (WO2009/060086).
Krieger describes compositions useful for treating infections which combine antibiotics and cationic peptides to provide enhanced antimicrobial effect. (Title, Abs.). The lysozyme of the instant claims is identified as one such antibiotic whose activity can be enhanced, as is niclosamide. [0024; 0156-58; Claim 40]. Krieger indicates that these cationic peptides and antibiotic agents can be formulated to provide synergistic antibiotic activity, permitting experimentation and adjustment of the amounts of each present in the compositions to achieve desired therapeutic effect. [0140]. Krieger indicates that the compositions described or suggested by their disclosure are advantageously formulated to be applied or administered via inhalation or intranasally, optionally with active agent concentrations in the range of 0.5-2%, or to deliver dosages from about 0.1-50mg/kg per day. [0218; 0241-42; 0244]. While not recited in the concentrations of Claims 24 and 28, Krieger does indicate that each of lysozyme and niclosamide are antibiotic agents which, in the context of the Krieger disclosure are taught as capable of having their dosages adjusted to obtain desired therapeutic effects. On this basis, a person of ordinary skill in the art would reasonably conclude that the amounts of each of lysozyme and niclosamide are result-effective variables that achieve the results each of the components referred to provide. As such, it would have been routine to optimize the amounts of these components within the total composition suggested by Krieger. See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (indicating that 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.).
Brown also discusses modifying the effect of various antimicrobial agents by adjusting the formulations which contain them. Specifically, Brown indicates that the antimicrobial activity of lysozyme and niclosamide may be adjusted by providing them in particular pharmaceutical formulations. [0012-13; 0104; 0113-14; 0244]. These too may be provided as aerosols for nasal administration via a nasal inhaler. [0184].
Serra describes pharmaceutical compositions suitably formulated to be compatible with a variety of routs of administration, including each of inhalation or intranasal administration. (Pg.13, L.3-10). Serra indicates these pharmaceutical compositions are commonly formulated with any of a variety of physiologically suitable excipients for providing pharmaceutical compositions including each of polysorbate 20, a compound having a hydrophobic component and a PEG component as required by Claim 15, as well as sucrose, representing a sugar per Claim 11. (Pg.13, L. 13-25). Serra indicates that such compositions contain about 5-95% active ingredient, or about 20-80% active in alternative embodiments. (Pg.13, L.22 – Pg.14, L.5).
The art at the time the instant application was filed therefore suggests pharmaceutical compositions which combine lysozyme and niclosamide in an composition for inhaled or intranasal administration. The art also establishes that nasal inhalers are devices known to be useful in the intranasal delivery of inhalable antimicrobial compositions containing potentiated lysozyme and niclosamide. The art also establishes that each of the sugars and compounds having a hydrophobic and PEG component were understood as physiologic excipients taught to be useful in the formulation of compositions for intranasal or inhaled routes of administration. It would have been prima facie obvious, given these teachings, to provide the claimed combination of niclosamide and lysozyme in a form for intranasal or inhaled administration because the art suggests doing precisely this. It would have been prima facie obvious to have incorporated excipients such as sucrose and polysorbate 20 in such a composition because the art suggests employing suitable pharmaceutical excipients, while also establishing that each of sucrose and polysorbate 20 are excipients known to be useful in the formulation of pharmaceutical compositions for intranasal or inhaled administration. As such, the claimed combination of niclosamide, lysozyme, sucrose, and polysorbate-20 provided in a form for inhaled or intranasal administration such as via a nasal inhaler appears to be the predictable combination of prior art elements according to their established functions as taught by each of the Krieger, Brown, and Serra references, with each performing the same function it had been known to perform and yielding no more than one would expect from such an arrangement. Such a combination is prima facie obvious. KSR v. Teleflex, 127 S.Ct. 1727, 1740 (2007) (quoting Sakraida v. A.G. Pro, 425 U.S. 273, 282 (1976)). “[W]hen the question is whether a patent claiming the combination of elements of prior art is obvious,” the relevant question is “whether the improvement is more than the predictable use of prior art elements according to their established functions.” (Id.). Addressing the issue of obviousness, the Supreme Court noted that the analysis under 35 USC 103 “need not seek out precise teachings directed to the specific subject matter of the challenged claim, for a court can take account of the inferences and creative steps that a person of ordinary skill in the art would employ.” KSR at 1741. The Court emphasized that “[a] person of ordinary skill is… a person of ordinary creativity, not an automaton.” Id. at 1742.
Consistent with this reasoning, it would have been prima facie obvious to have combined niclosamide, lysozyme, sucrose, and polysorbate-20 and provided such a composition in a form for inhaled or intranasal administration such as via a nasal inhaler, to arrive at compositions “yielding no more than one would expect from such an arrangement.”
Response to Arguments
Applicant's arguments filed 19 December 2025 have been fully considered but they are not persuasive.
Applicants assert that there is no single reference that teaches the claimed combination of lysozyme and niclosamide. This is unpersuasive because each of Krieger and Brown suggests such a combination. Applicants are reminded that it is unnecessary for art to describe a single embodiment containing all of the claimed elements when the entirety of the prior art disclosure is relied on to render a particular combination obvious. Art is art, not only for what it expressly teaches, but also for what it would reasonably suggest to the skilled artisan, including alternative or non-preferred embodiments. Merck & Co. v. Biocraft Laboratories, 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989). Here, each of the Krieger and Brown references identify lysozyme and niclosamide as individual antimicrobial agents, which the courts have long recognized are prima facie obvious to combine. In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). That each of the Kreiger and Brown references may include additional components is irrelevant, as these are not excluded from the instant claims. That Serra does not teach either lysozyme or niclosamide is irrelevant, as the Examiner has not asserted it does. The test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981). That each of the Lysozyme and niclosamide are recited with a variety of alternatives does nothing to establish the nonobviousness of selecting any one from such a listing. It is well settled that it is a matter of obviousness for one of ordinary skill in the art to select a particular component from among many disclosed by the prior art as long as it is taught that the selection will result in the disclosed effect, even when the possible selections number 1200 or in the thousands. Merck & Co., Inc. v. Biocraft Labs., Inc., 874 F.2d 804, 807 (Fed. Cir. 1989); In re Corkill, 771 F.2d 1496, 1500 (Fed. Cir. 1985).
Applicants assertion that the combination of lysozyme and niclosamide results in a synergistic antimicrobial effect which should countermand any findings of obviousness. This is unpersuasive because synergism is not per se unexpected. See In re Diamond, 360 F. 2d 214, 218 ( CCPA 1966). (“What section 103 requires is ‘unexpected synergism’ ... “ (pg. 216, n.7); “we attribute no magic status to synergism per se since it may be expected or unexpected"” (pg. 218)(emphasis added)). In this instance, the capacity of lysozyme to synergistically combine with a wide variety of antimicrobial agents is well known and long established. See, e.g., Alison M. McDermott, Antimicrobial Compounds in Tears, 117 Exp. Eye Res. 53, 56 (2013), Hong Yan & Robert W. Hancock, Synergistic Interactions Between Mammalian Antimicrobial Defense Peptides, 45 Antimicrob. Agents Chemother. 1558 (2001). As such, applicants assertion that another point of synergy demonstrated by combining lysozyme with another antimicrobial agent cannot be considered sufficient to render nonobvious their combination.
For at least these reasons, applicants arguments are unpersuasive.
Conclusion
No Claims are allowable.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SEAN M BASQUILL whose telephone number is (571)270-5862. The examiner can normally be reached Monday through Thursday, 5:30 AM to 4 PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Ali Soroush can be reached at (571) 272-9925. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SEAN M BASQUILL/Primary Examiner, Art Unit 1614