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
The amendment filed on 02/12/2026 is acknowledged.
Claims 8-9 are cancelled. Claims 1-7 and 10-20 are amended. Claims 21-22 are new.
Claims 1-7 and 10-22 are pending and being examined on the merits herein.
Priority
This instant application 17796568, filed on 07/29/2022, is a 371 of PCT/EP2021/052315, filed on 02/01/2021, and claims foreign priority to EP20305091.9, filed on 01/31/2020.
Information Disclosure Statement
No new information disclosure statement (IDS) has been filed.
Withdrawn Objections/Rejections
All previous claim Objection(s) / Rejection(s) as set forth in the previous Office action (mailed 11/13/2025) that are not repeated and/or maintained in the instant Office action are withdrawn, in light of applicant’s amendment and remark filed on 02/12/2026.
Claim Rejections - 35 USC § 102
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 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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-6 are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by Ahmed et al. (WO2019171253, Pub. Date 09/12/2019, filing date 03/04/2019 or earlier; same as CA3093036, 09/12/2019; PTO-892).
Ahmed throughout the reference teaches preparation and use of pharmaceutical formulations with high concentration antibodies (e.g., Abstract), constituting physical and chemical stability of the protein (e.g., Pg. 1, Background).
Ahmed teaches that the antibody compositions can be either in aqueous solution or lyophilized form (e.g., Pg. 70, Claim 37; Pg. 2, lines 1-5; Pg. 26, line 9; Pg. 6, Line 13; Pg. 42, Lines 4-5), and the liquid composition comprises a buffer, an antibody, a chelating agent, and a surfactant (e.g., Pg.10, Lines 24-27) with pharmaceutically acceptable carrier such as phosphate buffered saline solution or water (e.g., Pg. 24, Lines 16-20), indicating that antibody in the composition can be a human antibody, a humanized antibody, or a chimeric antibody; In some embodiments, the antibody is a monoclonal antibody; In some embodiments, the antibody is of the human lgG1, IgG2, IgG3, IgG4, and other subclass (e.g., Pg. 4, Lines 28-31; Pg. 11, Lines 19-25) (corresponding to IgG1 antibody in instant claim 1), and the buffer is preferably an acetate buffer (e.g., Pg. 3, line 12; Pg. 32, Lines 3-4; Pg. 49, Table 1), and the pH of the composition can be in the range of about pH 4.0 to 6.0 (e.g., Pg. 28, Lines 26-27) (pH range end value 4.0 falling within the range of lower than 4.5 in instant claim 1; falling within range between 3.7 and 4.3 in instant claim 3), while the surfactant can be polysorbate, poloxamer, sodium dodecyl sulfate, polyethylene glycol, etc. (e.g., Pg. 31, Lines 1-14) (corresponding to surfactant in instant claims 4 and 6).
Ahmed exemplifies liquid formulations in examples 1-6 (Pg. 51, Table 3), wherein does not use citrate (corresponding to instant claim 2), and contains PS80 (as polysorbate 80, Pg. 40, Line 29) 0.2g/L (equal to 0.02%, taking water density as 1g/ml), falling within range of lower than about 0.1% in instant claim 5.
MPEP 2131.03.I states that "If the prior art discloses a point within the claimed range, the prior art anticipates the claim." UCB, Inc. v. Actavis Labs. UT, Inc., 65 F.4th 679, 687, 2023 USPQ2d 448 (Fed. Cir. 2023). Thus, pH ranges or surfactant amount in instant claims 1, 3, and 5 are anticipated.
MPEP 2144.01 points out "[I]n considering the disclosure of a reference, it is proper to take into account not only specific teachings of the reference but also the inferences which one skilled in the art would reasonably be expected to draw therefrom." In re Preda, 401 F.2d 825, 826, 159 USPQ 342, 344 (CCPA 1968). Although Ahmed does not explicitly teach that the lyophilized form is powder, because Ahmed teaches that the composition can be administered directly into the blood stream, into muscle, into tissue, into fat, or into an internal organ. Suitable means for parenteral administration include subcutaneous (e.g., Pg. 72, Claims 52 and 55), intravenous, intraarterial, intraperitoneal, intrathecal, intraventricular, intraurethral, intrasternal, intracranial, intramuscular, intra-ossial, and intradermal. Suitable devices for parenteral administration include needle (including m icroneedle, m icroprojections, soluble needles and other micropore formation techniques) injectors, needle-free injectors and infusion techniques (e.g., Pg. 42, Lines 25-32), the powder form of lyophilized formulation would be anticipated by an artisan in the field.
“The use of patents as references is not limited to what the patentees describe as their own inventions or to the problems with which they are concerned. They are part of the literature of the art, relevant for all they contain.” In re Heck, 699 F.2d 1331, 1332-33, 216 USPQ 1038, 1039 (Fed. Cir. 1983), and "A reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill in the art, including nonpreferred embodiments." Merck & Co. v.Biocraft Labs., Inc. 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir. 1989), and "Disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments." In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971).
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 1-7, 10-18 and 21-22 are rejected under 35 U.S.C. 103 as being unpatentable over Ahmed et al. (WO2019171253, Pub. Date 09/12/2019, filing date 03/04/2019 or earlier; same as CA3093036, 09/12/2019; PTO-892) in view of Barry et al. (WO2008086395, IDS of 07/29/2022).
Ahmed throughout the reference teaches preparation and use of pharmaceutical formulations with high concentration antibodies, e.g., IgG1 antibody, constituting physical and chemical stability of the protein, that can be lyophilized from the liquid formulation, comprising aqueous medium such as water, acetate buffer, and the liquid formulation can have a pH between 4.0 to 6.0, as discussed and applied to claims 1-6 above, and incorporated herein.
Ahmed teaches that the acetate buffer can be at a concentration range from about 0.1 mM to about 100 mM. Preferably, about 10 mM among many other concentrations (e.g., Pg. 32, Lines 5-17), corresponding to instant claim 18.
Ahmed does not teach the liquid formulation does not comprise any surfactant as recited in instant claim 7, or a method of preparing an aerosol as recited in instant claim 10, droplets diameter of the aerosol as recited in instant claims 11-12, the method administering the aerosol is administered by inhalation as recited in instant claims 13 and 14, a nebulizer to produce aerosol as recited in instant claim 15, a kit for administering the aerosol as recited in instant claim 16, inhalation of aerosol via nebulizer as in instant claim 17, the method recited in instant claim 21, or the method of claim 22 with aerosol droplet diameter range.
Barry discloses ANTI-IL-13 antibody formulations (Title) in various examples, such as an aerosol comprising an antibody, 10 mM histidine buffer, with 5% sucrose, pH 6.0 (Pg. 41, Example 4; Pg. 57, Example 8, Table 6), and this formulation does not include citrate (Corresponding to instant claim 2); a liquid formulation comprising IL-13 antibody, 10mM acetate, 5% sucrose, pH 5.0 (or pH 5.5) (Pg. 57, Example 8, Table 6, No. 12-13) (Corresponding to instant claims 1 and 18), and No. 12-13 examples in Table 6 do not comprise any surfactant (Corresponding to instant claim 7). Barry indicates that the antibody can be selected from the group consisting of an IgG1 antibody, and IgG2 antibody, and an IgG4 antibody (Pg. 66, Claims 6 and 8) (corresponding to IgG1 antibody in instant claim 1), and the formulation further comprises a surfactant at a concentration of about 0% to about 0.2 % (Pg. 67, Claim 11) (Corresponding to instant claims 4 and 5,indicating 0% or free of surfactant is suitable, corresponding to instant claim 7). Barry 13urther indicates that the surfactant is selected from the group consisting of polysorbate-20, polysorbate-40, polysorbate-60, polysorbate-65, polysorbate-80, polysorbate-85, and combinations thereof (Pg. 67, Claim 12) (Corresponding to polysorbates in instant claim 6).
Barry indicates that the liquid formulation can be prepared as a liquid and then is dried, e.g., by lyophilization or spray-drying, prior to storage, and the dried formulation can be used as a dry compound, e.g., as an aerosol or powder (corresponding to instant claim 10 (i) step). Barry teaches the lyophilized formulation can be reconstituted as a liquid or an aerosol formulation (Pg. 66, Claims 1-2) (corresponding to instant claim 10 (ii) step). Barry exemplifies preparing aerosol of the liquid formulation (Pg. 20, Example 4), aerosolized by a commercially-available nebulizer (Pg. 20, Lines 9-13) (Corresponding to instant claim 10 (iii) step and claim 15). Barry characterizes the aerosol particles from a PARI LC Plus nebulizer by median of the distribution of airborne particle mass with respect to aerodynamic diameter as the mass median aerodynamic diameter (MMAD), and size distribution of droplets/particles, and other parameters measured by an Anderson Cascade Impactor (ACI) (Pg. 62, Example 12, top), presenting the mass median aerodynamic diameters at 3.45 um and 3.37 um, and aerosol droplet fine particle fraction (FPF) below 4.7 um are as 0.44 and 0.39 respectively (Pg. 62, Example 12, Lines 8-16, Table 9) (corresponding to from about 0.5 to about 5 um in instant claims 10 and 22; from about 0.5 um to about 4 um in instant claim 11; from about 0.5 um to about 3 um in instant claim 12).
Further regarding the droplet diameters are interpreted as intended use or property of the formulation, which has already been taught by prior art. The droplet diameters would necessarily present as inherent property of the formulation, or would be capable of being achieved as the same intended method of use being carried out.
Barry discloses the antibody formulation can be administered to a subject in need of treatment, e.g., inflammatory disease (e.g., Pg. 8, line 25), using many methods known in the art, including inhalation by nebulization, or injection (Pg. 9, Lines 18-19) to allow the formulation be delivered in the form of an aerosol spray from a pressured container or dispenser that contains a suitable propellant, e.g., a gas such as carbon dioxide, or a nebulizer (Pg. 31, Lines 13-25) (Corresponding to instant claims 13-14 and 17), and Barry specifies that a suitable container can be a nebulizer (Pg. 29, Lines 8-10), which can obviously be considered as a kit for administering the formulation in aerosol form comprising a container comprising the liquid formulation and the nebulizer capable of producing aerosol as recited in instant claim 16. Since Barry teaches a suitable propellant, e.g., a pressured container like nebulizer, makes the aerosol spray possible, it is obvious to the nebulizer comprising the liquid formulation upon reconstitution would be capable of nebulizing the liquid formulation to produce aerosol as instant claim 15.
Barry teaches the lyophilized powder or aerosol can be reconstituted to its original or another concentration, e.g., using water, a buffer, or other appropriate liquid (Pg. 15, Lines 20-25), suggesting original buffer, e.g., acetate buffer and pH range can be suitable for the reconstituted formulation (Corresponding to the method in instant claim 21), or appropriate volume of diluent (e.g., sterile water for injection, buffered saline), for delivery via inhalation in a somewhat concentrated formulation so as to provide a sufficient dose in a limited volume of aerosol for inspiration, using methods known in the art to adapt the dosage delivered to the method of delivery, e.g., a jet nebulizer or a metered aerosol (e.g., Pg. 19 bottom – Pg. 20 top) (corresponding to instant claim 22).
It would have been prima facie obvious for person having ordinary skill in the art (PHOSITA) to combine the teaching from Barry and Ahmed prior to the effective filing date to arrive at the current invention. Because Ahmed and Barry both direct to antibody (e.g., IgG1 antibody) compositions suitable for lyophilization, while Ahmed teaches that the composition can constitute high concentration of antibodies with stability in lyophilization and storage, Barry teaches that lyophilized compositions can be reconstituted for aerosol inhalation using nebulizers, it would have motivated artisans in the field to expand the administering method of Ahmed with Barry, because inhalation via nebulization is obviously more convenient than parenteral administration method, especially we all experienced how critical and inconvenient of vaccination process was during COVID pandemic, user-friendly inhalation nebulizer producing effective aerosol would have provided reasonable expectation of success. This renders obviousness as “use of known technique to improve similar devices (methods, or products) in the same way” or as “applying a known technique to a known device (method, or product) ready for improvement to yield predictable results”. See MPEP §2143. (I)(C) and (I)(D), or as combining prior art elements according to known methods to yield predictable results, see In Supreme Court KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007).
Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). MPEP §2144.05(I) states that “A prima facie case of obviousness typically exists when the ranges of a claimed composition overlap the ranges disclosed in the prior art.” See In re Peterson, 315 F.3d 1325, 1329 (Fed. Cir. 2003). For this instance, pH and particle diameters overlap with those in prior art. MPEP §2144.05 (II) states that “[i]t would have been prima facie obvious for one of ordinary skill in the art to optimize additive amount through nothing more than “routine experimentation,” because of a reasonable expectation of success resulting from the optimization for desirable features of intended use of the composition. See Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382; In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969).
Claims 19-20 are rejected under 35 U.S.C. 103 as being unpatentable over Ahmed et al. (WO2019171253, Pub. Date 09/12/2019, filing date 03/04/2019 or earlier; same as CA3093036, 09/12/2019; PTO-892) in view of Barry et al. (WO2008086395, IDS of 07/29/2022), as applied to claims 1-7 and 10-18 above, further in view of Rodrigueza et al. (CA 2890875, 05/08/2014, in record of 07/31/2025).
Combined teachings of Ahmed and Barry teach the liquid antibody formulation that can be lyophilized powder and reconstituted to produce aerosol via nebulizer, wherein the liquid formulation comprises IgG1 antibody, buffer (e.g., 10 mM acetate buffer), aqueous medium such as water, with or without surfactants, and the liquid formulation can be pH between 4.0 to 6.0, with specific droplet diameters from about 0.5 um to about 5 um as disclosed above in great detail and incorporated herein.
Ahmed and Barry do not indicate polydispersity index and various featured percentages of the monomer of antibody or antibody derivative determined by DLS as recited in instant claim 19, or particle size ranges in defined volume determined by FCM as recited in instant claim 20.
Rodrigueza directs to cancer therapies, compositions, and methods of using the same, wherein the therapies comprising the administration of oligomers and liposome formulations of oligomers (Abstract). Rodrigueza teaches that amphoteric liposomes are a class of liposomes having anionic or neutral charge at about pH 7.5 and cationic charge at pH 4 [00269], and the drug molecule may be partially or totally embedded in the lipid portion of the liposome, encapsulated with the lipid bilayer or present in the aqueous interior of the liposome or both [00271]. Rodrigueza teaches that drugs suitable for the composition such as chemotherapeutic agents including antibodies (e.g., alemtuzumab, IgG1k anti CD52 antibody [Table 1]), or antibody-like agents, inhibitors of kinases, cell surface receptors, proteins/enzymes [0075], epitope [0068] (fragment of a protein [0069], and many others as listed in great detail [00200-00239; Table 1], and the composition may be administered orally, parenterally, by inhalation spray, topically, rectally, nasally, intraocularly, buccally, vaginally, or via an implanted reservoir [00397], using carriers including polyoxyethylene, polysorbate 60, mineral oil, and many others [00404]. In Example 1 Rodrigueza exemplifies MOCHOL being a pH-titratable lipid positively charged at pH 4 during manufacturing, actively binding and thus encapsulating the negatively-charged PNT100 (24-base oligonucleotide fragment [00169], SEQ ID NO:1250, [00189]) within the liposome interior. When the pH is adjusted to physiological (near neutral in body conditions), MOCHOL becomes uncharged releasing unencapsulated PNT100 from the outer surface of the liposomes [00448]. Rodrigueza discloses the method step by step in detail of manufacturing and explains the mechanism [00450-00465], specifying that sodium acetate/acetic acid is chosen to maintain pH at 4 during mixing because it would allow for proton redistribution between inside and outside of the liposomes after adjustment to physiological pH with the shift buffer.
Rodrigueza teaches that polydispersity index can range from 0.0 (homogeneous) to 1.0 (heterogeneous) for the size distribution of liposomal formulations [00272]. Average diameter of particles ranges from 141-198 nm in Prep 1-3 and 5-6 measured by Malvern Zetasizer 3000HSA [00447, Table 2], which are all below 2 um (corresponding to instant claim 20), and polydispersity index is within 0.09-0.36 [00447, Table 2], which are all less than 0.5 (corresponding to instant claim 19). MPEP 2145 II. states that “prima facie obviousness is not rebutted by merely recognizing additional advantages or latent properties present but not recognized in the prior art”, see In re Baxter Travenol Labs., 952 F.2d 388, 21 USPQ2d 1281 (Fed. Cir. 1991). For this instance, because polydispersity index and particle sizes are taught by prior art, the other relevant properties such as the values of polydispersity percentage, mass percentage, and intensity percentage of a monomer antibody or antibody derivative could obviously be easily measured and recognized in instant claim.
It would have been prima facie obvious for one of ordinary skill in the art to incorporate the teaching from Rodrigueza into the composition/method taught by Ahmed and Barry prior to the effective filing date to arrive at the current invention. Because the Ahmed, Barry and Rodrigueza share common active agents in the compositions, and both Barry and Rodrigueza teach the compositions can be administered by inhalation in aerosol form, and the compositions taught by combined teachings of Ahmed and Barry have pH lower than 4.5, while Rodrigueza teaches the method and formulation that can encapsule the drug in low pH (e.g., pH 4) and release the drug in physiological condition (e.g., pH 7.4) as spontaneous simple switch to facilitate drug delivery, that would provide an artisan in the field reasonable expectation of success of implementing this additional desirable feature of polydispersity index and particle size distribution into the composition. This renders obviousness as combining prior art elements according to known methods to yield predictable results, see In Supreme Court KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007); Or “use of known technique to improve similar devices (methods, or products) in the same way” or as “applying a known technique to a known device (method, or product) ready for improvement to yield predictable results”. See MPEP §2143. (I)(C) and (I)(D).
Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). MPEP §2144.05(I) states that “A prima facie case of obviousness typically exists when the ranges of a claimed composition overlap the ranges disclosed in the prior art.” See In re Peterson, 315 F.3d 1325, 1329 (Fed. Cir. 2003). For this instance, polydispersity index, and particle number all overlap with those taught by prior art. Furthermore, “[i]t would have been prima facie obvious for one of ordinary skill in the art to optimize additive amount through nothing more than “routine experimentation,” because of a reasonable expectation of success resulting from the optimization for desirable features of intended use of the composition (MPEP §2144.05 (II)). See Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382; In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969).
Response to Arguments
Applicant’s remarks/arguments filed on 02/12/2026 have been fully considered.
Applicant’s arguments with respect to art rejections have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
Please refer to the entire office action presented above as a complete response to the arguments.
Conclusion
No claim is allowed.
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 DONGXIU ZHANG SPIERING whose telephone number is (703)756-4796. The examiner can normally be reached 7:30am-5:00pm (Except for Fridays).
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, SUE X. LIU can be reached at (571)272-5539. 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.
/DX.Z./Examiner, Art Unit 1616
/SUE X LIU/Supervisory Patent Examiner, Art Unit 1616
Prosecution Insights