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 .
DETAILED ACTION
Response to Amendment
Status of the Claims
Receipt of Applicant’s response, filed 20 Mar 2026 has been entered.
Claims 1, 7, 14, 26, 28, 29, 31, 34, 35, and 47 remain pending in the application.
Claims 1 and 7 are amended.
Claims 2-6, 8-13, 15-25, 27, 30, 32, 33, 36-46, and 48-51 are cancelled.
Claims 34, 35 and 47 are withdrawn from further consideration by the examiner, pursuant to 37 CFR 1.142(b), as being drawn to a non-elected invention / species.
Claims 1, 7, 14, 26, 28, 29 and 31 are under consideration to the extent of the elected species, i.e., that the antibody is bevacizumab, the angiogenesis inhibitor is bevacizumab, the stabilizer is trehalose, the dispersant is L-leucine, the buffer is phosphate buffer and the API is cisplatin.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 13 Oct 2025 and 07 Jan 2026 are in compliance with the provisions of 37 CFR 1.97, except where noted. Accordingly, the information disclosure statement is being considered by the examiner.
Rejections Withdrawn
Rejections Pursuant to 35 USC § 112
The rejections of claims pursuant to 35 U.S.C. 112(b) set forth in the Non-Final Office Action mailed 01 Oct 2025 are hereby withdrawn in light of applicants amendment of the claims.
Rejections Pursuant to Double Patenting
The rejection pursuant to Double Patenting set forth in the Non-Final Office Action mailed 01 Oct 2025 is hereby withdrawn in light of applicant’s amendment of the claims, and in favor of the new grounds of rejection set forth below.
Rejections Maintained – in modified form
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.
The rejection below was made previously and has been modified below to address the amended claim limitations.
Claims 1, 7, 14, 26 and 29 are rejected under 35 U.S.C. 103 as being unpatentable over DeHaan et al. (US 2015/0136130, published 21 May 2015).
DeHaan teaches inhalable dry powders comprising respirable dry particles that contain at least one therapeutic agent (title, [0008]). DeHaan teaches therapeutic agents such as the antibody bevacizumab ([0150], [0299]) and cisplatin ([0151], [0176]), rendering it obvious to include bevacizumab and cisplatin in dry powder formulations suitable for inhalation. DeHaan teaches that the total content of the therapeutic agent or agents in the respirable dry powder is at least 20%, at least 25%, at least 35%, at least 50%, at least 65% or at least 80% by weight ([0012]), rendering obvious the bevacizumab and cisplatin (small molecular API) in a dry powder formulation in the amounts of claim 1. DeHaan teaches the inclusion of excipients such as trehalose and leucine ([0034], [0164]), including L-leucine ([0166],[0382]) and teaches the excipients may be present in amounts such as less than 90%, 80%, 70%, 60%, 50%, 40% and 25% ([0168]) and teaches the specific range of 1-30% w/w for excipients ([0330]), rendering obvious the trehalose and L-leucine of instant claim 1. DeHaan teaches that the excipient and pharmaceutically therapeutic agent can independently be crystalline or amorphous or present in a combination of these forms ([0259]), rendering it obvious that different components may be crystalline or amorphous and thereby rendering obvious the crystalline/amorphous limitation of claim 1. DeHaan teaches spray drying ([0180], [0383]), rendering obvious the spray dried dispersion. DeHaan teaches the inclusion of a metal cation salt ([0008]) such as sodium phosphate and potassium phosphate ([0066], [0067]) where the cation salt is present at about 3% by weight or 5% by weight ([0012]), and teaches that spray drying particles requires that the ingredients be solubilized in solution ([0383]). The phosphate salts mentioned are buffers in solution, rendering obvious the inclusion of a phosphate buffer as in claims 7 and 14. DeHaan teaches that the powders can be fabricated with a preselected size distribution ([0193]) and teaches a Dv50 of a respirable size between about 0.5 μm and about 5 μm, rendering obvious instant claim 26. DeHaan teaches that the dose container may be a capsule ([0201], [0233]), rendering obvious claim 29.
DeHaan does not expressly teach selecting the bevacizumab, cisplatin, L-leucine, trehalose or phosphate buffer in the amounts recited for the dry powder formulation or the crystalline and amorphous forms with sufficient specificity to rise to the level of anticipation.
However, it would have been prima facie obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention to have formed a dry powder formulation with therapeutic agents bevacizumab and cisplatin in amounts such as at least 20%, at least 25%, at least 35%, at least 50%, at least 65% or at least 80% by weight and to have included trehalose and L-leucine from 1-30% w/w and metal salts such as sodium phosphate (i.e a phosphate buffer) at about 3% or 5% by weight and to have the components independently be crystalline or amorphous. One of ordinary skill in the art would have been motivated to do so as each of these components and amounts and forms are taught by DeHaan as suitable in inhalable dry powder formulations. One of ordinary skill in the art would have a reasonable expectation of forming an inhalable dry powder formulation with these components, as taught by DeHaan, since the modification of the prior art represents nothing more than the predictable use of prior art elements according to their established functions.
Accordingly, the instant claims are rendered prima facie obvious over the teachings of DeHaan.
Response to Arguments
Applicant's arguments filed 20 Mar 2026 have been fully considered but they are not persuasive. Applicant states that claim 1 now requires that L-leucine is crystalline while the bevacizumab, trehalose and small molecular API are amorphous but that DeHann in ([0259]) teaches that in the particles the monovalent metal cation salt is substantially in the crystalline phase (page 6 of remarks). Applicant further notes that leucine is an excipient and that DeHaan teaches formulations where the excipient is amorphous or predominately amorphous and DeHaan does not provide examples where the excipient is crystalline.
The examiner is not persuaded by these arguments and notes that in paragraph [0259] that DeHaan teaches that the “excipient and pharmaceutically therapeutic agent can independently be crystalline or amorphous or present in a combination of these forms.” Thus, DeHaan renders it obvious that the different components may be either amorphous or crystalline, independent of the other components in the composition. Thus, there is a prima facie case of obviousness for having the components in an crystalline or amorphous state, including where the L-leucine is crystalline and the bevacizumab, trehalose and API are amorphous. Even if DeHaan does not exhibit the leucine as crystalline, it is noted that DeHaan does not limit the leucine from being crystalline and it is not necessary for it to be exemplified for it to be obvious. The rejection was made under 35 U.S.C. 103 which requires that “a patent for a claimed invention may not be obtained… if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been prima facie 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.” “A person of ordinary skill in the art is also a person of ordinary creativity, not an automaton.” KSR, 550 U.S. at ___, 82 USPQ2d at 1397. “[I]n many cases a person of ordinary skill will be able to fit the teachings of multiple patents together like pieces of a puzzle.” Id. Office personnel may also take into account “the inferences and creative steps that a person of ordinary skill in the art would employ.” Id. At, 82 USPQ2d at 1396. While DeHaan may not provide a specific embodiment of the instantly claimed invention, the examiner maintains that the invention as claimed, including the amorphous and crystalline limitation, is nonetheless made obvious over DeHaan.
Claim 28 is rejected under 35 U.S.C. 103 as being unpatentable over DeHaan et al. (US 2015/0136130, published 21 May 2015) as applied to claims 1, 7, 14, 26 and 29 above and in view of Green (US 2016/0235667, published 18 Aug 2016).
The teachings of DeHaan are described supra.
While DeHaan teaches that the particles may have a preselected size distribution and renders obvious the d50 value, DeHaan does not explicitly teach the d10 and d90 values as required in claim 28. This deficiency is made up for in the teachings of Green.
Green teaches compositions for inhalation that are directed to pulmonary administration of a pharmaceutically active protein (abstract). Green teaches that uniform blends with narrow particle size distributions are desirable in the field of inhalation as this lends itself more easily to predictable pulmonary drug delivery ([0010]). Green teaches that spray drying is able to achieve uniform particle blends ([0011]). Green teaches suitable particle size ranges are D10≤6 μm, D50≤7 μm D90≤10 μm ([0025]). These values overlap with the particle sizes listed in claim 28, rendering obvious these ranges.
Therefore, it would have been prima facie obvious to one of ordinary skill in the
art, before the effective filing date of the claimed invention to have formed the inhalable dry powder formulation rendered obvious by DeHaan with particle sizes of D10≤6 μm, D50≤7 μm D90≤10 μm. Forming the particles with spray drying and a preselected size distribution where the Dv50 is about 0.5 μm and about 5 μm is known from DeHaan. It is further known from Green that spray drying is able to achieve uniform particle blends and that a narrow size distribution lends itself to predictable pulmonary drug delivery. Particle sizes of proteins ranging from D10≤6 μm, D50≤7 μm D90≤10 μm are known from Green. Thus, one of ordinary skill would recognize this size distribution as suitable for the particles formed from DeHaan as DeHaan already indicates particle sizes with Dv50 on the same order as taught by Green and further limiting the D10 and D90 would be obvious in order to achieve a narrow particle distribution and more predictable pulmonary drug delivery of the components.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, as evidenced by the references.
Claim 31 is rejected under 35 U.S.C. 103 as being unpatentable over DeHaan et al. (US 2015/0136130, published 21 May 2015) as applied to claims 1, 7, 14, 26 and 29 above and in view of Heslet et al. (US 2013/0216608, published 22 Aug 2013, listed on IDS filed 16 May 2023).
The teachings of DeHaan are described supra. DeHaan further teaches the use of a dry powder inhaler ([0203], [0233])
DeHaan does not teach a kit. This deficiency is made up for in the teachings of Heslet.
Heslet teaches compositions comprising one or more agents capable of inhibiting angiogenesis and that act as an active anti-cancer agent that are administered via inhalation as a dry powder (abstract). Heslet teaches suitable components for the composition include bevacizumab ([0064]) and cisplatin ([0085]). Heslet teaches that the medical packaging for the dosage may be a capsule ([0220]) and that the compounds of the invention are provided in a kit ([0218]).
Therefore, it would have been prima facie obvious to one of ordinary skill in the
art, before the effective filing date of the claimed invention to have formed the inhalable dry powder composition rendered obvious over DeHaan as a kit with a dry powder inhaler and capsules. Use of a dry powder inhaler and capsules are already known from the teachings of DeHaan. Dry powder formulations for inhalation that may contain components such as bevacizumab and cisplatin are similarly known from Heslet and the use of a kit with the components is taught by Heslet. Thus, it would have been obvious to form the inhalable dry powder formulation of DeHaan as a kit as such compositions are known as suitable for use with kits and it would be desirable to have the compositions presented in an easy to use manner for the end user.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, as evidenced by the references.
New Grounds of Rejections
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 1, 7, 14, 26, 28, 29 and 31 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 and 16-18 of copending Application No. 18/589,995 in view of DeHaan et al. (US 2015/0136130, published 21 May 2015).
Application 18/589,995 discloses a dry powder formulation suitable for administration via inhalation comprising angiogenesis inhibitors such as bevacizumab, a small molecular API such as cisplatin, a stabilizer such as trehalose and a dispersant such as L-leucine. The application further discloses a phosphate buffer. The application has the angiogenesis inhibitor from 1-90%, the API from 1-80%, the stabilizer from 10-90%, the dispersant from 2-40% and the buffer at less than 5%. The application recites particle sizes that overlap with the particle sizes of the instant claims, that the formulation is spray dried, the formulation in a capsule and a kit comprising a dry powder and one or more capsules.
The ‘995 application does not recite that the L-leucine is crystalline and the bevacizumab, trehalose, and cisplatin are amorphous. These deficiencies are made up for in the teachings of DeHaan.
The teachings of DeHaan are described supra.
Therefore, it would have been prima facie obvious to one of ordinary skill in the
art, before the effective filing date of the claimed invention to have formed the dry powder formulation with the L-leucine crystalline and the bevacizumab, trehalose, and cisplatin as amorphous. Dry powder formulations and spray drying and the same components of the reference claims are known from DeHaan. It is further known from DeHaan that the excipient and pharmaceutically therapeutic agent can independently be crystalline or amorphous or present in a combination of these forms, thus rendering it obvious that the composition can have various forms as crystalline and amorphous. Similar dry compositions as the reference claims are known from DeHaan, providing a reasonable expectation of success in having the components as amorpohous and crystalline.
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claims are 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 extension fee 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 date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to EDWIN C MITCHELL whose telephone number is (571)272-7007. The examiner can normally be reached Mon-Fri 8:00-5:00.
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/E.C.M./Examiner, Art Unit 1619 /BENNETT M CELSA/Primary Examiner, Art Unit 1600
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