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
Claims 1-10 are currently pending.
Claims 1-10 are being examined on the merits.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
This application is a 371 of PCT/CN2023/084611 (03/29/2023) as reflected in the filing receipt issued September 27, 2024.
Information Disclosure Statement
The Information Disclosure Statement(s) submitted on May 07,2025 is being considered by the Examiner.
Drawings
The drawings are objected to because the drawings are not legible. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Objections
Claim 5 appears to have a “0” after line 4 of the claim, which may be a typo and should be removed.
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.
Claim 1 and 4-9 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
For claim 1: the images of the structures are illegible, therefore it is unclear of what is being claimed.
For claim 4: The phrase "preferably -45°C” and “preferably 4 hours” 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 claim 5: The phrase " preferably 1 hour" and “preferably 1°C/min” 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 claim 6: : The phrase " preferably 6-25 " and “preferably 1°C/min”, “preferably 4 hours”, and “preferably 25 Pa” 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 claim 7: The phrase "preferably -25 to -20°C, most preferably -20 °C" , “more preferably 43 hours or 49 hours ”, and “preferably 25 Pa” 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 claim 8: The phrase " preferably 2-6 hours, preferably 2-4 hours", and “preferably 25 Pa” 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 claim 9: The phrase " preferably 20-30°C ", and “preferably 25 Pa” 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).
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 1-10 are rejected under 35 U.S.C 103 as being unpatentable over Fang et al (US20200129633A1; Published on April 30, 2020, cited in IDS) in view of Zhao et al (US20140199286A1; Published on July 17,2014) and Qin et al (US20170112944A1; Published on April 27,2017, cited in IDS).
With regards to claims 1-9, Fang et al throughout teaches an antibody conjugate formulation to inhibit the aggregation and isomerization of antibodies, and prevent the degradation of an antibody product therein, being a stable injectable pharmaceutical formulation.
For claim 1: Fang teaches that liquid medicine (reads on ADC formulation of the claim) was placed in a lyophilization chamber to perform the lyophilization process. The lyophilization included sequential steps of pre-freezing, primary drying and secondary drying (Fang paragraph 0111).
Fang further discloses that the pre-freezing temperature and rate is −45° C and 1° C./min (starting from −5° C) (Fang paragraph 0039). Fang discloses that the pre-freezing has set time (reads on cooling of the claim) range of 10 to 40 minutes and the holding time of 60 to 180 minutes (converts to 1 hour and 3 hours) with temperature range as discussed above, reads on step 1 cooling process and a holding process (Fang paragraph 0111).
Primary drying, also known as main drying, is the main stage of sample lyophilization (Fang paragraph 0039). Fang teaches that primary drying has a set time of 100 minutes (converts to 1.67 hours) and a holding time of 2160 minutes (converts to 36 hours), which reads on step 2 heating process and holding process (Fang paragraph 0111). Higher temperature and higher vacuum degree will accelerate the lyophilization (reads on freeze-drying of the claim) during the primary drying process, while the collapse risk of the product is increased at the meantime (Fang paragraph 0039).
Fang further discloses that secondary drying with higher temperature (25-40° C) (Fang paragraph 0039). The secondary drying has a set time (reads on the heating process) of 60 minutes (converts to 1 hour) and a holding time of 450 minutes (converts to 7.5 hours), which reads on step 3 a heating process and a holding process.
Fang also discloses that antibody drug conjugate preparations were prepared with a buffer containing 10 mM succinic acid-sodium succinate with pH 4.8 to 5.8 (Fang paragraph 131). Fang also teaches that some embodiments, the pharmaceutical composition further comprises saccharide which can be selected from the group consisting of glucose, sucrose, trehalose (Fang paragraph 0015). Fang discloses pharmaceutical composition with 1-20 mg/mL antibody drug conjugate; b) 10-20 mM succinate buffer, pH 5.0-5.5;(c) 60 mg/mL sucrose; and(d) 0.05-0.4 mg/mL polysorbate 20 (Fang paragraph 0034).
For claim 2: Fang also teaches that 10 mM succinic acid (sodium succinate) (converts to 10mmol/L) at pH 5.0 to 5.5 as buffer, containing 60 mg/mL sucrose, 0.2 mg/mL polysorbate 20 and 20 mg/mL ADC-12 (reads on the GQ1001 of the claim) (Fang paragraph 0130).
For claim 3: Fang discloses that the pre-freezing has set time (reads on cooling of the claim) for range of 10-40 minutes and the holding time of 60 to 180 minutes (converts to 1 hour and 3 hours) with temperature range as discussed above, reads on step 1 cooling process and a holding process (Fang paragraph 0111).
For claims 4 and 5: Fang teaches step 1, which is pre-freezing temperature, and the pre-freezing rate and temperature is −45° C. and 1° C./min (starting from −5° C) (Fang paragraph 0039). Fang further exemplifies the parameters for each step as discussed above, where the temperature and holding process for step 1 set time for range of 10-40 minutes and the holding time of 60 to 180 minutes (converts to from 1 hour to 3 hours) at normal pressure (Fang paragraph 0111).
For claims 6 and 7: Fang teaches that the primary drying has a set time of 100 minutes (converts to 1.67 hours) and a holding time of 2160 minutes (converts to 36 hours), which reads on step 2 heating process and holding process (Fang paragraph 0111). Fang further discloses that temperature of the primary drying of the present disclosure can be a temperature conventional in the art, for example, −27° C. to −20° C., preferably −20° C (Fang paragraph 0038).
For claims 8 and 9 The secondary drying has a set of 60 minutes (converts to 1 hour) and a holding time of 450 minutes (converts to 7.5 hours), which reads on step 3 a heating process and a holding process. Fang further discloses that the temperature for secondary drying is 25°C (Fang paragraph 0111).
Fang does not appear to explicitly teach the pressure for primary drying, structure and compound as recited in claim 1. Fang also does not explicitly teach the temperature rate, time, and pressure of the freeze-drying process recited in claims 3, 6-9. Fang also does not explicitly teach full-tank freeze-drying process, recited in claim 10. Qin and Zhao references are relied upon for these disclosures. Their teachings are set forth herein below.
Qin et al throughout teaches a conjugate and preparation method thereof, a pharmaceutical composition comprising the conjugate and use of the pharmaceutical composition (Qin abstract).
For claim 1: Qin teaches an ADC, which is GQ1001, with structure as disclosed in the instant claims, where X in ligase recognition sequence LPXT of is glutamic acid (E) or any other natural/unnatural amino acids: x is —OH or —NH2 group (Qin claim 22). Qin also teaches LA3 comprises 1 to 100 series-connected structure units which are selected from the group consisting of one or more glycine and alanine (Qin claim 11 and paragraph 0036). Qin further states that b is independently 0 or 1, that is, LA3 may be independently present or absent (Qin claim 11).
Zhao et al teaches a process for producing a lyophilized pharmaceutical composition a protein.
For claim 1: Zhao teaches the pressure of the chamber from 50 to 500 mT (6.67 Pa to 66.66 Pa) ( Zhao claim 87step iv). Zhao further discloses in step the primary drying parameters where the pressure of the chamber is not modified ( Zhao claim 87).
For claim 3: Zhao teaches process for producing lyophilized pharmaceutical composition containing a protein (reads on ADC of the claim (iii) reducing the temperature to an initial freezing temperature at a rate of 0.2° C. to 2.0° C. per minute (Zhao claim 1). Zhao also teaches in step six of claim 1 the pressure of the chamber is 50 to 500 mT (6.67 Pa to 66.66 Pa) (Zhao claim 1 step vi).
For claim 6 and 7: Zhao teaches a rate of 0.2° C. to 2.0° C. per minute (0.2° C /min converts to 12° C/h). Zhao further teaches increasing the temperature to a primary drying with the chamber pressure is 50 to 500 mT (6.67 Pa to 66.66 Pa) (Zhao claim 1 steps vi and vii).
For claim 8: Zhao teaches increasing the temperature to a secondary drying at a rate of 0.2° C. to 2.0° C. per minute (0.2° C /min converts to 12° C/h) and holding the temperature (Zhao claim 1 step viii).
For claim 9: Zhao teaches the increasing temperature of the secondary drying where the pressure of the chamber is 50 to 500 mT (6.67 Pa to 66.66 Pa) (Zhao claim 87 steps iv and vi).
For claim 10: Zhao recites placing one or more containers within a chamber of a lyophilizing unit (Zhao claim 1 step ii). The broadest reasonable interpretation of “full-tank” is the use of the freeze-drying chamber.
With regards to GQ1001 and substitutes of moiety (claims 1 and 2), as discussed above, Fang exemplifies the pre-freeze-drying and freeze-drying steps with ADC formulation using 10 mM succinic acid (sodium succinate) (converts to 10 mmol/L) at pH 5.5 as buffer, containing 60 mg/mL sucrose, 0.2 mg/mL polysorbate 20 and 20 mg/mL, as disclosed above. Qin discloses with structure as disclosed in the instant claims, where X in ligase recognition sequence LPXT of is glutamic acid (E) or any other natural/unnatural amino acids: x is —OH or —NH2 group (Qin claim 22). Qin also teaches LA3 comprises 1 to 100 series-connected structure units as discussed above. One of ordinary skill in the art would have found it prima facie obvious before the effective filing date of the instant invention to combine the teachings of Fang and Qin to incorporate the steps taught by Fang with the structure moiety taught by Qin. One of ordinary skill in the art would have been motivated to do so for achieving quality characteristics and therapeutic index as desired for the storage for long time periods without deterioration. One of ordinary skill in the art would have had a reasonable expectation of success in doing so because both references teach antibody drug conjugate preparations with stability and kept characteristics within long storage periods without deterioration.
With regards to the freeze-drying process, Fang exemplifies freeze-drying steps where the cooling process, primary drying, and secondary drying with various temperatures and holding times, as discussed above. Zhao discloses temperature rate and pressure range from 50 to 500mT (6.67 Pa to 66.66 Pa), as discussed above. One of ordinary skill in the art would have found it prima facie obvious before the effective filing date of the instant invention to optimize the teachings of the freeze-drying steps taught by Fang with the temperature rate and pressure taught by Zhao for pharmaceutical composition storage. One of ordinary skill in the art would have been motivated to do so for pressure ranges are known to be used for pharmaceutical freeze-drying methods such as those disclosed by Fang.
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, because the combined teachings of the prior art references is fairly suggestive of the claimed invention.
Conclusion
Claims 1-10 are rejected. No claims are allowed.
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/J.A.E./ Examiner, Art Unit 1616
/MONICA A SHIN/ Primary Examiner, Art Unit 1616
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