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 .
Priority
This application filed 05/16/2023 is a National Stage entry of PCT/IL2021/051368, international filing date: 11/17/2021. PCT/IL2021/051368 claims priority from provisional application 63114556, filed 11/17/2020.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on May 16, 2023 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Claim Rejections - 35 USC § 103
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 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.
Claims 50-52, 66-69 are rejected under 35 U.S.C. 103 as being unpatentable over Gilon, Chaim hereinafter Gilon (WO2019/175867A1; published 19 September 2019; reference provided in the IDS) in view of Jonathan M. Collins, hereinafter Collins (WO2017/070512A1; published 27 April 2017).
Claims 50-52, 66, 67, 69 are directed to a method of solid phase peptide synthesis in a reaction chamber, comprising a stirring apparatus having at least two blades, a reaction mixture of functionalized polymeric resin beads, at least one solvent, at least one reactant, in contact with the blades and achieving rotational rates of at least 600 rpm, shear rate of at least 3-103 sec-1, wherein the reaction chamber is heated to allow the temperature range of 40 °C-100 °C, in the range of 50 °C-100 °C, thereby performing at least one cycle of solid phase peptide synthesis.
Gilon teaches solid phase peptide synthesis, the method comprises the steps: providing a reactor comprising a reaction chamber and a stirring apparatus comprising an impeller having at least two blades rotatable about an axis; inserting beads of functionalized polymeric resin and at least one solvent into the reactor to provide a reaction mixture, wherein the reaction mixture is in contact with the rotatable blades; inserting at least one protected monomeric organic molecule and at least one coupling agent into the reaction chamber and spinning the impeller, thereby forming a coupling product of the protected monomeric organic molecule and the resin; washing excess of said protected monomeric organic molecule; and; inserting at least one deprotecting reagent into the reaction chamber and spinning the impeller, thereby removing at least one protecting group from the coupling product, forming a coupling product of the deprotected monomeric organic molecule and the resin, thereby completing a cycle in the solid phase synthesis of a polymeric organic molecule; and spinning the impeller for a period of time, at a rotational rate of at least 600 rounds per minute, while maintaining a sheer rate of at least 3-103 sec-1, thereby performing at least one step of the solid phase synthesis (see page 6; lines 1-8). Gilon teaches a coupling capacity of 0.2 – 0.6 mmol/g (see claim 15 and claim 19). Gilon teaches that solid phase synthesis method is for synthesis of polymeric organic molecules selected from the group consisting of peptide…glycoproteins and proteoglycans (see page 12; line 23 and page 13; lines 1-14). Gilon teaches that methods to improve the technique of solid phase peptide synthesis (SPSS) include thermal methods e.g. microwave and heating (see page 3, line 9).
Gilon does not teach heating the reaction chamber to 40 °C – 100 °C and 50 °C - 100 °C.
Collins teaches improvements in solid phase synthesis of peptides (SPSS), wherein heating the vessel contents to between about 81 °C – 99 °C accelerates the deprotection step of peptide synthesis (see claims 14, 17; [0044]). Colin teaches that the deprotection step can be carried out by heating the compositions to at least about 60 °C and in some cases to between about 81 °C - 99 °C [0045]. Since Collins discloses a temperature range which touches or overlaps the claimed range, the rejection is based on 35 U.S.C. 103 which takes differences into account." Titanium Metals Corp. v. Banner, 778 F.2d 775, 227 USPQ 773 (Fed. Cir. 1985) (Claims to titanium (Ti) alloy with 0.8% nickel (Ni) and 0.3% molybdenum (Mo) were not anticipated by, although they were held obvious over, a graph in a Russian article on Ti-Mo-Ni alloys in which the graph contained an actual data point corresponding to a Ti alloy containing 0.25% Mo and 0.75% Ni). See MPEP § 2131.03 (III).
Obviousness can be established by combining or modifying the teachings of the prior art to
produce the claimed invention where there is some teaching, suggestion, or motivation to do so. In re
Kahn, 441 F.3d 977, 986, 78 USPQ2d 1329, 1335 (Fed. Cir. 2006) (discussing rationale underlying the
motivation-suggestion-teaching test as a guard against using hindsight in an obviousness analysis).
Consequently, 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 modify the method of Gilon, by heating the reaction as in the instant application. One motivated to do so would have a reasonable expectation of success as Gilon explicitly teaches heating to improve the technique of solid phase peptide synthesis (see page 3, line 9). Thus, one would have recognized that applying the teaching of Collins to the method of Gilon would have yielded predictable results and improved the technique of SPSS (See MPEP § 2143 I(A)(D)).
Claims 53-65 are rejected under 35 U.S.C. 103 as being unpatentable over Gilon, Chaim hereinafter Gilon (WO2019/175867A1; published 19 September 2019; reference provided in the IDS) in view of Jonathan M. Collins, hereinafter Collins (WO2017/070512A1; published 27 April 2017) further in view of Mark Simon et al., hereinafter Simon (US2018/0057525A1; published 1 March 2018; reference provided in the IDS).
Claims 53-55 are directed to a heating assembly in contact with the external enclosure of the reaction chamber. Embodiments of the specification disclose heating assembly is a circulating fluid bath ([0021], line 24).
Claims 56-58 and 60 are directed to a semipermeable glass fritted disc in the internal cavity.
Claims 59, 61-65 are directed to the reactor further comprising a proximal conduit end wherein the proximal conduit end is connected to a portion of the enclosure. The proximal conduit end is connected to a first distal conduit end and to a second distal conduit end wherein the first distal conduit end is connected to an inert gas source, wherein the second distal conduit end is connected directly or indirectly to a vacuum pump, wherein the reactor further comprises a three-way valve configured to monitor flow of liquids and gases.
As noted above, Gilon teaches solid phase peptide synthesis in a reaction chamber and stirring apparatus wherein the stirring apparatus comprises an impeller having at least two blades with a rotational rate of at least 600 rounds per minute, shear rate of at least 3-103 sec-1 (see page 6; lines 1-8).
Gilon does not teach heating the reaction chamber to 40 °C – 100 °C and 50 °C - 100 °C. Gilon does not teach a glass frit for draining liquids from the reaction vessel and vacuum or inert gas in SPSS.
Collins teaches improvements in solid phase synthesis of peptides wherein heating the vessel contents to between about 81 °C – 99 °C accelerates the deprotection step of peptide synthesis (see claims 14, 17; [0044]). Colin teaches that the deprotection step can be carried out by heating the compositions to at least about 60 °C and in some cases to between about 81 °C - 99 °C [0045]. Collins teaches microwave radiation to heat the deprotection step (claim 15). Microwave source (diode) heats the reaction vessel (see Figure 6 and 7). Colin teaches a vacuum source connected to the reaction vessel [0018]. Colins teaches that deprotection step is accelerated further by pulling the vacuum while heating the vessel contents [0044]. Colin teaches that in Fig 7, the vessel 22 includes a frit 52 (typically made of glass). The frit 52 permits liquids to be drained from the reaction vessel 22. Colin teaches that in Fig 7, the spray head 53 delivers compositions to the reaction vessel 22. Notably, other equivalent fixtures can be selected by the skilled person without undue experimentation. In particular, Fig 7 illustrates a nitrogen supply 54 which is connected to a plurality of supply bottles 55 which are illustrated as Erlenmeyer flasks [0053]. Collins teaches that nitrogen pressure transfers all reagents in the reaction vessel and provides an inert environment during synthesis [0062]. Collins teaches that Nitrogen is helpful because it is relatively inexpensive but other inert gases, including noble gases can be used for this purpose [0054]. Collins teaches that in Figure 6, the nitrogen supply and the metered loop can connect to the processor 47 so that the processor 47 can control the manner in which the compositions are dispensed from the vessels 55 to the reaction vessel 52. Collins teaches that the schematic line connections (64 and 65) are in practice, a combination of tubes (pipes), valves, and controls for those lines; e.g., in practice line 64 represents a connection between a valve or manifold in line 58, a controller for that line, and the processor 47. The same relationships hold true for the line 65 between the nitrogen supply 54 and the processor 47. Collins teaches that the reaction vessel system utilizes up to 25 stock solutions for amino acids and seven reagent ports that can perform the following functions: main wash, secondary wash, deprotection, capping, activator, activator base, and cleavage. The system uses nitrogen pressure for transfer of all reagents and to provide an inert environment during synthesis. The system uses metered sample loops for precise delivery of all solutions [0062].
Collins does not teach a fluid bath or heating jacket for heating the reaction vessel.
Simon teaches achieving fast peptide synthesis time by heating [0063]. Simon teaches that any suitable method of heating may be used to increase the temperature of the contents. For example, heating zone may comprise a liquid bath (e.g. water bath), a resistive heater, a gas-convection-based heating element or any other suitable heater [0065]. Simon teaches that the reactor immersed in a temperature-controlled bath, allows reagents to be heated in a consistent and controlled manner immediately before reaching the resin bed [0095].
Obviousness can be established by combining or modifying the teachings of the prior art to
produce the claimed invention where there is some teaching, suggestion, or motivation to do so. In re
Kahn, 441 F.3d 977, 986, 78 USPQ2d 1329, 1335 (Fed. Cir. 2006) (discussing rationale underlying the
motivation-suggestion-teaching test as a guard against using hindsight in an obviousness analysis).
Consequently, 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 modify the method of Gilon, by using a glass frit as in the instant application. Gilon teaches that resin beads can fracture into smaller and smaller particles which can clog filters and interrupt the synthesis process (see page 3, line 24). Additionally, Gilon teaches that heating improves the technique of solid phase peptide synthesis (see page 3, line 9). Although Gilon uses the method of microwave-mediated heating, Simon teaches that the reactor immersed in a temperature-controlled bath, allows reagents to be heated in a consistent and controlled manner immediately before reaching the resin bed [0095]. Thus, one would have recognized that applying the teaching of Collins and Simon to the method of Gilon would have yielded predictable results and improved and accelerated the technique of SPSS (See MPEP § 2143 I(A)(D)).
Conclusion
No claim is allowed.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ARCHANA VARADARAJ whose telephone number is (571)272-2366. The examiner can normally be reached Monday-Friday 10:00am-5:00pm.
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, Melissa Fisher can be reached at 5712707430. 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.
/ARCHANA VARADARAJ/ Examiner, Art Unit 1658
/LIANKO G GARYU/ Supervisory Patent Examiner, Art Unit 1654