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 .
Priority
This application, filed 03/08/2024 is a National Stage entry of PCT/CN2022/117610, International Filing Date: 09/07/2022. PCT/CN2022/117610 claims foreign priority to 202111051190.6, filed 09/08/2021. A certified copy of the foreign priority application is of record.
Status of Claims
Claims 1, 4-16, 21, 24, 27-29, and 31 are pending as of the response filed on 8/4/26. Claims 2-3, 17-20, 22-23, 25-26, and 30 have been canceled.
Applicant's election with traverse of invention I, claims 1, 4-16, 21, 24, and 27-28 in the reply filed on 8/4/26 is acknowledged. However, upon further consideration, the restriction between inventions I and II is withdrawn. Claims 1, 4-16, 21, 24, 27-29, and 31 are included for examination. The species election requirement is also withdrawn in consideration of the amended claims filed on 8/4/26.
In the restriction response filed on 8/4/26, Applicants have stated Ex. 4 reproduced in part shows the claimed preparation exhibits advantageous quality and stability compared with formulations employing different lyophilization excipients. However, this evidence is not found persuasive, because the formulations of Ex. 4 contain very specific excipients, while at least claims 1 and 4 are considerably broader in scope, and are not limited to the specific excipients present in this Ex.
Claims 1, 4-16, 21, 24, 27-29, and 31 were examined. Claims 1, 4-16, 21, 24, 27-29, and 31 are rejected.
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.
Claims 5-9, 11-13, 15-16, 24, and 28 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.
Claims 5-9, 11-13, 15-16, 24, and 28 recite the term “preferably”, and/or “more preferably”, which introduces indefiniteness into the claims, because it is uncertain if the scope is limited to the embodiments or limitations following “preferably” or “more preferably”, or should be given the broad recitation before these terms.
Regarding claims 7, 11, and 15, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
For the sake of compact prosecution, the claim language following “preferably”, “more preferably”, and “such as” have not been examined with respect to prior art.
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) 1, 4-5, 7-12, 21, 27, 29, and 31 is/are rejected under 35 U.S.C. 103 as being unpatentable over Huang et. al., WO 2017025057 A1, publ. 2/16/2017, in view of Catania et. al., US 5633006, patented 5/27/1997, and Lee et. al., WO 2014163215, publ. 10/9/2014 (English language translation referred to for rejection below).
Huang teaches conjugate compounds or pharmaceutically acceptable salts thereof composed of a payload and two or more kinds of cell-interacting molecules capable of specifically binding to a cell surface receptor (title & abstract; para [002], [006]). Huang includes folate and TRPV6 receptors as exemplary cell surface receptors that the compounds bind to (para [013], [071]). Huang teaches the compounds to contain a cleavable linker that is cleaved by hydrolysis, enzymes, reduction, or a change in pH, and in some embodiments the linker is cleaved at an acidic environment of pH=6.5 or lower (para [056]). Huang further teaches pharmaceutical compositions comprising the conjugate compounds and pharmaceutically acceptable carriers, wherein the composition is suitable for intravenous, oral, subcutaneous, intramuscular, parenteral, or intraventricular administration (para [025], [0101]). Huang includes the conjugate compound LDC10B, shown below, as exemplary (para [034], [090], [092], Fig. 1):
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. This compound is identical to the dual ligand-drug conjugate of instant claim 1. Huang further teaches LDC10B can function synergistically to destroy cancer cells expressing both TRPV6 and folate receptors (para [099]). Huang teaches the compositions in various dosage forms, including liquids, tablets, pills, capsules, gels, slurries (para [0104]). Huang teaches acceptable carriers to include water, such as sterile water, NaCl solution, isotonic dextrose solution; isotonic agents such as NaCl or dextrose; buffers, such as phosphate or citrate buffers; polyols, such as glycerol, propylene glycol, or PEG; sucrose, glucose, and mannitol (para [0105-0110]). Huang teaches administering a conjugate compound as disclosed above for treating a disease in a subject, including cancer, wherein the cancers to be treated include breast cancer, lung cancer, prostate cancer, renal cancer, ovarian cancer, gastric cancer, uterine cancer, among others (para [027-028]).
Huang doesn’t explicitly teach an excipient that is lyophilized.
Catania teaches a wide variety of pharmaceutical agents exhibit a bitter taste during or immediately after oral administration, which can be an issue as oral administration is generally a preferred route of administration (col. 1, lines 16-51).
Lee et. al. teaches a pharmaceutical composition comprising a bitter tasting active ingredient, a sugar alcohol, and a sugar, wherein the combination of sugar alcohol and sugar provide a bitter taste masking effect (abstract; para [1], [13-15]). Lee et. al. teaches the sugar alcohol to be selected from xylitol, mannitol, sorbitol, maltitol, erythritol, sorbitol, arabitol, galactitol, and lactitol; and the sugar is selected from sucrose, lactose, maltose, sucralose, trehalose, and cellobiose (para [16-17]). Lee et. al. teaches the combination of sugar, sugar alcohol, and active agent are freeze-dried, i.e., lyophilized (para [20-23]). Lee et. al. teaches tablet dosage forms (para [25], [37], [43], [51-52]), e.g., drug delivery device. Lee additionally includes purified water as a solvent for preparing the freeze-dried preparation (para [67], [73], [76]).
It would have been prima facie obvious to one of ordinary skill in the art, before the effective filing date of the claims to have arrived at the pharmaceutical preparation of the instant claims, comprising the dual ligand-drug conjugate targeting a folate receptor and TRPV6 receptor having the structural formula shown in claim 1, water, a buffer, and a lyophilized excipient comprising a polyol and a saccharide in consideration of the combined teachings of Huang, Catania, and Lee. Huang teaches compositions comprising the dual ligand-drug conjugate targeting a folate receptor and TRPV6 receptor having the structural formula shown in claim 1, and acceptable excipients such as water, such as sterile water, NaCl solution, isotonic dextrose solution; isotonic agents such as NaCl or dextrose; buffers, such as phosphate or citrate buffers; polyols, such as glycerol, propylene glycol, or PEG; sucrose, glucose, and mannitol. Huang further teaches administering the compositions to treat various cancers, but doesn’t teach lyophilized excipients. Catania teaches many active agents possess a bitter taste, while Lee teaches a pharmaceutical preparation for masking the bitter taste associated with active agents comprising the combination of a polyol and a saccharide, in lyophilized form. Therefore, one of ordinary skill in the art would have been motivated to have incorporated the composition of Huang comprising a dual ligand-drug conjugate targeting a folate receptor and TRPV6 receptor having the structural formula shown in claim 1 into the composition taught by Lee, since many active agents are taught to exhibit a bitter taste, and the preparation of Lee would solve such an issue. As Lee doesn’t limit the type of active agent for incorporation into the preparation, one of ordinary skill in the art would have had a reasonable expectation of success in incorporating the composition of Huang comprising a dual ligand-drug conjugate of claim 1 into the preparation of Lee.
Regarding instant claim 5, both Huang and Lee teach sterile or purified water as a solvent.
Regarding instant claim 7, Huang teaches conjugate compounds to contain a cleavable linker that is cleaved by hydrolysis, enzymes, reduction, or a change in pH, and in some embodiments the linker is cleaved at an acidic environment of pH=6.5 or lower. Therefore, it would have been prima facie obvious to have arrived at a pH of 6.5, and have had a reasonable expectation of success.
Regarding instant claims 8, 10, 11, and 12, Lee teaches suitable sugar alcohols to include xylitol, mannitol, sorbitol, maltitol, erythritol, sorbitol, arabitol, galactitol, and lactitol; and the sugar is selected from sucrose, lactose, maltose, sucralose, trehalose, and cellobiose. Therefore, it would have been prima facie obvious to have arrived at the polyol and saccharide recited in these claims, and have had a reasonable expectation of success.
Claim Rejections-Nonstatutory 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, 4-16, 21, 24, 27-29, and 31 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4-6, 9, 11-13, 15-17, 25, 28, 31-32, and 34-35 of copending Application No. 18703208 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims are drawn to a pharmaceutical preparation comprising an active drug which is a ligand-drug conjugate, a freeze-dried (lyophilized) excipient, a pH regulator (buffer) and a solvent. Copending claim 17 recites the ligand-drug conjugate as a dual ligand-drug conjugate, which broadly includes the dual ligand-drug conjugate recited by instant claim 1. The concentration of active drug in both claims is overlapping (copending claim 5 & instant claim 6); the pH range in both preparations are overlapping (copending claim 16 & instant claim 7); the freeze-dried excipient includes a polyol and saccharide (copending claims 11-12, & instant claim 1). Additionally, both sets of claims recite a liquid preparation comprising the freeze-dried preparation reconstituted in water (copending claim 28 & instant claim 24); a prefilled syringe containing the preparation (copending claim 32 & instant claim 28); and a method of treatment comprising administering the preparation (copending claims 34-35 & instant claims 29 & 31). Therefore, the instant and copending claims are not patentably distinct.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Information Disclosure Statements
The IDS filed on 6/5/24, 12/10/24, 8/14/25, and 7/7/26 have been considered.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SARAH PIHONAK whose telephone number is (571)270-7710. The examiner can normally be reached Monday-Friday 9:00-5:30 EST.
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SARAH . PIHONAK
Primary Examiner
Art Unit 1627
/SARAH PIHONAK/Primary Examiner, Art Unit 1627
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