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 .
Election/Restrictions
Applicant’s election without traverse of Group II, claims 14 and 15, in the reply filed on March 30, 2026 is acknowledged. Claims 1-13 and 16-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected inventions, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on March 30, 2026.
Applicant is reminded that upon the cancelation of claims to a non-elected invention, the inventorship must be corrected in compliance with 37 CFR 1.48(a) if one or more of the currently named inventors is no longer an inventor of at least one claim remaining in the application. A request to correct inventorship under 37 CFR 1.48(a) must be accompanied by an application data sheet in accordance with 37 CFR 1.76 that identifies each inventor by his or her legal name and by the processing fee required under 37 CFR 1.17(i).
Claim Objections
Claims 14 and 15 are objected to because of the following informalities: “the obtained particles” in the last limitation lacks antecedent basis. Also these claims depend from a withdrawn claim and should be rewritten in independent form. The abbreviation “API” should be written out in the first instance. Appropriate corrections are required.
Claim Rejections - 35 USC § 112
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.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim14 and 15 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
The term “small molecular API” in claims 14 and 15 is a relative term which renders the claim indefinite. The term “small molecular API” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. The disclosure uses the term “small molecular API” throughout, but without any definition or elaboration. The only “small molecular API” disclosed are “cisplatin, carboplatin, topotecan, paclitaxel, erlotinib, and combinations thereof” (para.0244, pre-grant publication US 2024/0197628). However these are but several examples of a presumably vast class of pharmaceutical active agents. While various scientists/authors and entities circumscribe a “small molecule” drug as having a molecular weight or size within some defined range, there appears no single, established range across the field of pharmaceutical industry.
For the purposes of examination now this claim term is construed as any non-macromolecular active agent.
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.
Claim(s) 14 and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Brudnicki (US 2020/0022917).
Brudnicki teaches preparing therapeutic agent in powder form, e.g., aflibercept, or a “small molecule VEGF antagonist” (paras.0076, 0082, 0098, 0104; see entire document including title; abstract; paras.0001, 0008-09, 0019, 0055-56, 0061-63, 0083-84, 0102, 0104-05, 0120-22, 0131). “In one aspect, the invention provides a method of manufacturing the subject formulated pharmaceutical powder by ‘spray drying’ the precursor aqueous solution containing the subject protein and any additional excipients” (para. 0112). The inlet and the outlet temperatures for the spray dryer chamber, and the spray or drying gas, are such that the feedstock solution forms a powder (para.0113; see paras.0138, 0142, 0144, Examples 1, 3, 4). “[T]he formulated pharmaceutical powder is formed by subjecting the subject feedstock to atomization to form a mist of atomized droplets, and then applying heat to the mist of atomized droplets to form the formulated pharmaceutical powder comprising the protein.” (Para.0114). The formulations “remain stable and biologically active at ambient and physiological temperatures for an extended period of time” (para.0001).
For the small molecular active pharmaceutical ingredient, Brudnicki expressly teaches using stabilizers of “small molecules (≤ 200 grams per mole)”, including inositol, tryptophan, etc. (para.0061; see paras.0059) which are therapeutic active pharmaceutical ingredients. Furthermore suitable active agents include “small molecules that inhibit VEGF - stimulated tyrosine kinases , including for example lapatinib , sunitinib , sorafenib , axitinib , and paxopanib” (para.0098; see para.0104).
For the stabilizing agent, Brudnicki teaches the specific combination of mannitol with isoleucine or proline (claims 9, 22, 36). Applicant describes as a mannitol as a “stabilizer” and isoleucine as a “dispersant”, respectively (paras.0174, 0182, pre-grant publication US 2024/0197628).
Brudnicki does not specifically disclose a specific process wherein the feedstock solution comprises both the angiogenesis inhibitor protein such as aflibercept in combination with a small molecule VEGF- inhibitor, or inositol or tryptophan, as in claim 14, or preparing separate solutions of an angiogenesis inhibitor protein and a small molecular active agent as in claim 15.
However it would have been prima facie obvious for one having ordinary skill in the art before the effective filing date to do so. The skilled person would have been motivated to do so. “It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.” MPEP §2144.06 (I) (citations omitted). Here Brudnicki expressly teaches using multiple stabilizers, including combinations of mannitol and isoleucine or proline, as well as other “small molecule” stabilizers such as trehalose, inositol, and tryptophan, which are therapeutic agents.
Regarding claim 15 it is noted that making separable what was known in the prior art where removability or access was desirable, has been held to be obvious. See MPEP § 2144.04 (V)(C) (citations omitted). Here the skilled person would have recognize that “small molecules … for example lapatinib , sunitinib , sorafenib , axitinib , and paxopanib” and “[m]acromolecular inhibitors …bevacizumab , the Fab fragment ranibizumab , the trap aflibercept[sic] , and the PEGylated aptamer pegaptanib” could require different solvents for optimal feedstock solution for spray drying. Therefore preparing separate spray drying solutions by dissolution of the small active agent in a first solvent and another solution by dissolution of the angiogenesis inhibitor would have been prima facie obvious to one of ordinary skill in the art.
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 14 and 15 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 34 and 35 (03/20/2026) of copending Application No. 18/253,190 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other because both claim sets are drawn to identical spray drying process comprising steps (a) through (d). The difference is that the ‘190 application’s claims require bevacizumab, trehalose, and L-leucine as the angiogenesis inhibitor, the stabilizer and the dispersant, each at respective concentration ranges. Therefore the ‘190 application’s claims anticipate the present claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to H. S. PARK whose telephone number is (571)270-5258. The examiner can normally be reached on weekdays.
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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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/H. SARAH PARK/Primary Examiner, Art Unit 1614
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