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 .
Withdrawn Objections/Rejections
The rejections of claims 44 and 61 are withdrawn in view of the cancellation of the
claims.
The previous rejections claims 42, 47, 49, and 73 under 35 USC § 103 are withdrawn in view of the claim amendments.
The rejections claims 42, 47, 49, and 73 on the grounds of nonstatutory double patenting over the claims Application 17/909,697 in view of Gelfand are withdrawn in view of the abandonment of Application 17/909,697.
Claim Status
Applicants' amendments and arguments filed 12/15/2025 have been fully considered.
Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The
following rejections and/or objections are either reiterated or newly applied. They constitute the
complete set presently being applied to the instant application.
Claims 1-41, 43-46, 48, 50-72, 74, 77-78, and 86 are cancelled.
Claims 89-93 are newly added.
Claims 75-76, 79-85, and 87-88 are withdrawn.
Claims 42, 47, 49, 73, and 89-93 are under current examination. The claims were read in view of the species election of lysin B and isoamylase as the one or more antibacterial lytic proteins, elected in the reply filed on 05/28/2025.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 12/15/2025 has been considered by the Examiner.
New Rejections Necessitated by Claim Amendments
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.
Claims 42, 47, 49, 73, and 89-93 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Claim 42 recites “a liposome comprising a phosphatidylserine targeting moiety”. This is indefinite as it is unclear if the claim requires a liposome comprising a) a targeting moiety which targets phosphatidylserine or b) a targeting moiety which is phosphatidylserine. For purposes of examination and applying prior art, it is interpreted that the liposome of the instant claim comprises phosphatidylserine, consistent with the specification at pg. 17, lines 10-17.
Claims 47, 49, 73, and 89-93 are rejected under 35 U.S.C. 112(b) by virtue of their dependency on indefinite claim 42 and failure to cure the deficiency noted above.
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 42, 47, 49, 73, and 89-93 are rejected under 35 U.S.C. 103 as being unpatentable over Sharma et al. (US 2017/0136102 A1, published May 18, 2017; of record), hereafter “Sharma” in view of Rashid et al. (“Assembly of α-Glucan by GlgE and GlgB in Mycobacteria and Streptomycetes” Biochemistry 2016, 55, 3270-3284; of record), hereafter “Rashid”, and Fraziano et al. (US 2010/0178330 A1, published July 15, 2010), hereafter “Fraziano”.
Regarding instant claim 42, Sharma teaches methods and compositions for the treatment of mycobacteria infections, particularly tuberculosis infections (abstract, paragraph [0005]). Subjects are administered an outer membrane acting biological (paragraph [0005], claim 1), which is taught to be phage LysB (paragraph [0005], claim 11), an antibacterial lytic protein. Formulations of interest include those for liposomal delivery (paragraphs [0139]-[0140]).
Regarding instant claims 47, 49, and 92, as noted above, Sharma teaches the inclusion of the antibacterial lytic protein of phage LysB, a lysin.
Regarding instant claim 73, the compositions of Sharma reduce mycobacteria (paragraph [0005]); LysB biologics are particularly taught to reduce mycobacteria (paragraph [0015]).
Regarding instant claim 91, Sharma teaches administration can be via inhalation (paragraph [0028]) and via aerosol for delivery to the lungs (paragraphs [0128] and [0132]), thus indicating that the composition is formulated for administration via inhalation.
Regarding instant claim 93, Sharma teaches an outer membrane acting biologic that is specifically D29 phage LysB, selected because it is highly bactericidal compared to other phages (claim 11, paragraphs [0063], [0102], and [0197]).
Sharma does not teach the inclusion of the elected species of an antibacterial lytic protein of isoamylase.
Rashid teaches that actinomycetes, such as mycobacteria, synthesize α-glucan with α-1,4 linkages and α-1,6 branching to help evade immune responses and to store carbon (abstract). The capsule coating mycobacteria cells is mainly composed of a glycogen-like α-glucan; this might contribute to the virulence of M. tuberculosis by binding to DC-SIGN to evade the host immune response (see Introduction, particularly pg. 3271, paragraph 1). Rashid further teaches that isoamylase hydrolyzes α-1,6-linked branch points (Figure 3 on pg. 3273) and is particularly taught to hydrolyze such linkages in intrachain branching catalyzed by M. tuberculosis GlgB enzymes (Figure 10 on pg. 3281).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant invention to modify the compositions of Sharma to include isoamylase. One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success to incorporate an agent capable of hydrolyzing α-1,6 branching points present in the capsule coating of mycobacteria cells, particularly M. tuberculosis, and disrupt the mycobacteria’s ability to evade immune response, as suggested by Rashid. There is a reasonable expectation of success as the compositions of Sharma are used for the treatment of mycobacteria infections, particularly tuberculosis infections (abstract), and Sharma teaches that cocktails of biologics that affect the same bacterial hosts can be used in pharmaceutical compositions (paragraph [0134]).
Sharma does not teach that the liposome comprises a phosphatidylcholine targeting moiety (instant claim 42). Sharma further does not teach that the liposome comprises a Z-average mean particle diameter of from about 75 nm to about 750 nm (instant claim 89) or from about 75 nm to about 250 nm (instant claim 90).
Fraziano teaches liposomes comprising phosphatidylserine molecules within an outer lipid layer for the transport of active agents for the treatment of pulmonary infections including Mycobacterium tuberculosis (abstract, claims 1, 61-63, 70, and 73-74). The outside phosphatidylserine presence allows an efficient phagocytosis by macrophages and cells which represent possible targets for viral and pulmonary infections (i.e. Mycobacterium sp); phagocytosis through recognition of phosphatidylserine molecules further has the advantage of reducing the tissue damaging inflammatory response (paragraph [0023]). Fraziano further teaches that it is preferable that a pharmaceutical composition comprising the liposomes is formulated as an aerosol, and that the best therapeutic effectiveness is obtained using particulates having sizes from 100 nm to 50 nm, depending on the selected lung area for therapy (paragraph [0043]).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant invention to modify the liposomes taught by Sharma to include outer phosphatidylserine molecules, as suggested by Fraziano. One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success achieve a liposome that provides efficient phagocytosis by macrophages and target cells for the treatment of pulmonary infections such as Mycobacterium tuberculosis while reducing the tissue damaging inflammatory response, as suggested by Fraziano. There is a reasonable expectation of success as the compositions of Sharma are used for the treatment of mycobacteria infections, particularly tuberculosis infections (abstract).
It would further have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant invention to modify the liposomes taught by Sharma to have a size of 50 nm to 100 nm (overlapping the diameter of the instant claims), as suggested by Fraziano. One of ordinary skill in the art would be motivated to do so to achieve a particle size that achieves good therapeutic effectiveness in liposomal pharmaceutical compositions for the delivery of agents to treat lung infections, particularly Mycobacterium tuberculosis; Fraziano further suggests that the liposomal size can be optimized to achieve a size that is delivered to a desired lung area. There is a reasonable expectation of success as Sharma teaches liposomal formulations for the treatment of mycobacteria infections, particularly tuberculosis infections (abstract), and that the formulations can be administered via aerosol (paragraph [0128]). Further, per MPEP 2144.05 I, “In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990)” and per MPEP 2144.05 II. A, “"[W]here 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." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)”.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 42, 47, 49, 73, and 89-93 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 9-10, 29, 31, 64-67, and 87 of copending Application No. 18/855,101 in view of Sharma et al. (US 2017/0136102 A1, published May 18, 2017; of record).
Both the instant claims and those of copending Application No. 18/855,101 are directed to composition comprising a liposome comprising a combination of Lysin B and isoamylase (one or more antibacterial lytic proteins). The claims of copending Application No. 18/855,101 further recite that the composition is used in a method of treating a bacterial infection caused by a mycobacterium, indicating that the proteins are capable of killing a mycobacterium, and that the composition is administered via inhalation (indicating that it is formulated for administration via inhalation). Both sets of claims further recite that the supramolecular structure comprises a Z-average mean particle of from 75 nm to 750 nm and 75 to 250 nm the inclusion of a targeting moiety comprising phosphatidylserine.
The claims of copending Application No. 18/855,101 do not recite that the Lysin B is D29 Lysin B, as required by instant claim 93.
Sharma teaches methods and compositions for the treatment of mycobacteria infections (abstract, paragraph [0005]). Subjects are administered an outer membrane acting biological (paragraph [0005], claim 1), which is taught to be phage LysB (paragraph [0005], claim 11), an antibacterial lytic protein. Formulations of interest include those for liposomal delivery (paragraphs [0139]-[0140]). Sharma teaches an outer membrane acting biologic that is specifically D29 phage LysB, selected because it is highly bactericidal compared to other phages (claim 11, paragraphs [0063], [0102], and [0197]).
It would have been prima facie obvious to one of ordinary skill in the art to modify the Lysin B in the composition claimed in copending Application No. 18/855,101 with the specific D29 lysin B taught by Sharma. One of ordinary skill in the art would be motivated to select a Lysin B known in the art to be highly bactericidal, particularly as the composition of copending Application No. 18/855,101 is used in treating bacterial infections.
This is a provisional nonstatutory double patenting rejection.
Claims 42, 47, 49, 73, and 89-93 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 44-45, 47-48, 54, 95, and 101 of copending Application No. 18/863,056 in view of Sharma et al. (US 2017/0136102 A1, published May 18, 2017; of record).
Both the instant claims and those of copending Application No. 18/863,056 are directed to a composition comprising the antibacterial lytic proteins Lysin B and isoamylase. The claims of copending Application No. 18/863,056 further recite that the composition is used in a method of treating a bacterial infection caused by a mycobacterium, indicating that the proteins are capable of killing a mycobacterium, that the composition is administer via inhalation (indicating that it is formulated for administration via inhalation), and that the Lysin B and isoamylase can be comprised in a supramolecular structure of a liposome wherein the supramolecular structure comprises a Z-average mean particle diameter of from 75 nm to 250 nm and comprises a targeting moiety comprising phosphatidylserine.
The claims of copending Application No. 18/863,056 do not recite that the Lysin B is D29 Lysin B, as required by instant claim 93.
Sharma teaches methods and compositions for the treatment of mycobacteria infections (abstract, paragraph [0005]). Subjects are administered an outer membrane acting biological (paragraph [0005], claim 1), which is taught to be phage LysB (paragraph [0005], claim 11), an antibacterial lytic protein. Formulations of interest include those for liposomal delivery (paragraphs [0139]-[0140]). Sharma teaches an outer membrane acting biologic that is specifically D29 phage LysB, selected because it is highly bactericidal compared to other phages (claim 11, paragraphs [0063], [0102], and [0197]).
It would have been prima facie obvious to one of ordinary skill in the art to modify the lysin b in the composition claimed in copending Application No. 18/863,056 with the specific D29 lysin B taught by Sharma. One of ordinary skill in the art would be motivated to select a lysin B known in the art to be highly bactericidal, particularly as the composition of copending Application No. 18/863,056 is used in treating bacterial infections.
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
Applicant’s arguments filed 12/15/2025 have been fully considered.
Regarding the claim rejections under 35 U.S.C. § 103, Applicant argues that independent claim 42 has been amended to recite a composition comprising a liposome that includes a phosphatidylserine targeting moiety and a cargo containing one or more antibacterial lytic proteins; none of the cited references teaches or suggests a composition containing a phosphatidylserine targeting moiety.
In response, the Examiner notes that, as detailed above, the previous claim rejections under 35 U.S.C. § 103 have been withdrawn, and new rejections which address the amended claim limitations have been applied. In summary, the prior art of Fraziano provides motivation to the ordinary skilled artisan to incorporate phosphatidylserine in an outer lipid layer of liposomes used for the treatment of pulmonary infections including Mycobacterium tuberculosis in order to achieve an efficient phagocytosis by macrophages and a reduction in the tissue damaging inflammatory response.
Regarding the nonstatutory double patenting rejections, Applicant notes that the effective filing date of the instant application predates the effective filing dates of the ‘101 Application and ‘056 Application, and thus Applicant requests that the Office withdraw the provisional rejections and permit the present application to proceed to grant once the claims are otherwise in condition for allowance (see, M.P.E.P. § 804, subsection I.B.1 (b)(i)).
In response, the Examiner notes that per MPEP 804 I.B., “A provisional double patenting rejection should be made and maintained by the examiner until the rejection has been obviated or is no longer applicable except as noted below”, and MPEP 804 I.B.1 (b)(i) states (emphasis added), “If a provisional nonstatutory double patenting rejection is the only rejection remaining in an application having the earlier patent term filing date, the examiner should withdraw the rejection in the application having the earlier patent term filing date and permit that application to issue as a patent, thereby converting the provisional nonstatutory double patenting rejection in the other application into a nonstatutory double patenting rejection upon issuance of the patent.” As detailed above, the provisional nonstatutory double patenting rejections are not the only rejections remaining, and thus the provisional nonstatutory rejections are not withdrawn at this time.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 JUDITH M KAMM whose telephone number is (703)756-4575. The examiner can normally be reached M-F 8:00 am-4:30 pm EST.
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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.
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/BETHANY P BARHAM/Supervisory Patent Examiner, Art Unit 1611
/J.M.K./Examiner, Art Unit 1611