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 .
Status of the Application
The claims of 7 August 2024 are entered.
The election of 1 June 2026 is entered.
Claims 1-77 have been canceled. Claims 78-90 are pending. Claims 87-90 are withdrawn without traverse. Claims 78-86 are being examined on the merits.
Election/Restrictions
Applicant’s election without traverse of Group I in the reply filed on 1 June 2026 is acknowledged.
Claims 87-90 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 1 June 2026.
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 78-86 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.
Claim 78 recites the limitation "the reactor" in line 9. There is insufficient antecedent basis for this limitation in the claim. The dependent claims do not remedy this deficiency.
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.
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 78, 79, and 81-83 are rejected under 35 U.S.C. 103 as being unpatentable over Biosynthesis (https://www.biosyn.com/tew/solid-phase-peptide-synthesis.aspx, published 18 July 2013, hereafter referred to as Biosynthesis) and KR101014799 B1 (published 15 February 2011, hereafter referred to as ‘799).
The Biosynthesis describes a synthetic pathway for solid phase peptide synthesis:
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(see e.g. Figure 1). The Biosynthesis art also describes that UV detection is useful for monitoring Fmoc coupling (see e.g. p.6). Implied in the activation and coupling steps are that streams of base amino acids are combined with an activator. The activated amino acid is added to a plurality of peptides already present on the solid support. Deprotection is also conducted to remove the protecting group found on the peptide after coupling in step 2. The cyclic nature of the reaction process also allows for second amino
The difference between Biosynthesis and the claimed invention is that Biosynthesis does not describe merging of streams.
The ‘799 application describes a reaction vessel for peptide synthesis where reactant/solvent storage tanks 10 are used to mix reactants in a reaction vessel, i.e. mixing of streams:
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.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention that the process of Biosynthesis could have readily been adapted such that the mixing of streams provided by ‘799 is utilized in the reaction steps of Biosynthesis in order to provide a process for adding amino acid residues to a peptide. In this merged process, first streams having an amino acid with a protecting group are sent down a first conduit, a second stream containing an activating agent is sent down a second conduit, the two are mixed in order to activate the amino acid and couple to a plurality of peptides immobilized on a solid support, and the resultant peptide deprotected and monitored via UV to continue addition of amino acid residues to the peptides. The rationale to utilize Biosynthesis comes from its outline of known solid-phase synthesis techniques, and the ‘799 art sets forth reaction vessels that could be utilized for flow of reagents in such a system, including mixing of reagents prior to application to a support. There would have been a reasonable expectation of success because pathways for solid phase synthesis were well known in the art, and in this case the skilled artisan merely had to utilize the mixing process of ‘799 and alter timing, well within the level of ordinary skill in the art. The invention would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
With respect to claim 79, as noted above the process of Biosynthesis is cyclical, such that one of ordinary skill in the art when attempting to prepare a peptide would have found it obvious to add in a second amino acid with second protecting groups and merge with another stream containing a second amino acid activating agent then exposing the mixture to the previously immobilized peptides on a solid support to further extend the length of the peptide.
With respect to claim 81, Biosynthesis discloses carbodiimides for amino acid activation, as does ‘799.
With respect to claim 82, ’79 discloses uronium compounds for amino acid activation (see e.g. p. 2).
With respect to claims 83 and 84, Biosynthesis suggests polystyrene for the solid support (see e.g. “Peptide Synthesis Chemistries: A Comparison”).
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.
1. Claims 78, 79, and 83-85 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, and 9-12 of U.S. Patent No. 11,878,996 B2 in view of Menakuru et al. (US 8,535,947 B2, published 17 September 2013, hereafter referred to as ‘996).
The ‘996 patent claims a process for adding amino acid residues to a peptide by flowing a first stream comprising amino acids and a second stream comprising an activating agent such that the streams are mixed, then flowing to a reactor with a solid support containing immobilized peptides to add residues to the immobilized peptides (see e.g. claim 1). A deprotection agent is later passed over the mixture to remove protecting groups (see e.g. claim 6-8).
The difference between ‘996 and the claimed invention is that ‘996 does not claim an outlet stream from the reactor being transported through a UV detector to monitor absorbance.
The ‘947 patent describes a monitoring system to assess deprotection of Fmoc groups during peptide synthesis using a UV detector (see e.g. claims 1 and 9).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention that the process of ‘996 could have been modified by including the UV detection system of ‘947 in order to monitor the efficacy of the deprotection process. The rationale comes from the skilled artisan recognizing that solid-phase peptide synthesis techniques need very high efficacy in order to produce acceptable quantities of finalized peptides such that monitoring of deprotection processes is critical to assessing whether or not addition of subsequent amino acids should occur. There would have been a reasonable expectation of success because UV monitoring of deprotection steps was known in the art, and in this case the skilled artisan is merely adding one known step to another known process. The invention would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention. With respect to claim 79, ‘996 claims multiple addition steps (see e.g. claim 2).
With respect to claims 83-85, ‘996 claims a resin including PEG and microporous polystyrene resins (see e.g. claims 10-12).
2. Claims 78-85 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 and 10 of U.S. Patent No. 9,868,759 B2 in view of Menakuru et al. (US 8,535,947 B2, published 17 September 2013).
The ‘759 patent claims a process for adding amino acids to a peptide by flowing a first stream containing an amino acid and a second stream containing an activating agent such that they mix, then exposing the mixture to a plurality of peptides immobilized on a solid support (see e.g. claim 1). The ‘759 patent further claims flowing of protecting groups, including amine groups (see e.g. claims 15-19).
The difference between ‘759 and the claimed invention is that ‘759 does not claim flowing of a deprotecting agent or monitoring via a UV detector.
The relevance of the ‘947 patent is set forth above, which also includes flowing of deprotecting agents.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention that the process of ‘759 involving protected amino acids and solid-phase synthesis could have been altered by including the ‘947 step of flowing a deprotecting agent and monitoring via UV detectors. The rationale comes from general knowledge of solid phase synthesis techniques, such that the process of ‘759 involving protected amino acids by necessity would require deprotection to allow further coupling or finalizing of peptides with amine groups and monitoring to ensure proper deprotection and coupling. There would have been a reasonable expectation of success because these are known steps in solid-phase peptide synthesis. The invention would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
With respect to claim 79, the ‘759 patent claims multiple rounds of amino acid addition (see e.g. claim 10).
With respect to claims 80-82, the ‘759 patent claims alkaline liquids, carbodiimides, and uronium compounds as activating agents (see e.g. claim 2).
With respect to claims 83-85, the ‘759 patent claims resins including PEG and microporous polystyrene (see e.g. claims 3-5).
3. Claims 78, 81, and 82 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 46 of copending Application No. 17/747,952 in view of Menakuru et al. (US 8,535,947 B2, published 17 September 2013).
The ‘952 application claims a method of operating a peptide synthesis system by flowing a first stream containing an amino acid to a mixing region, flowing a second stream containing an activating agent to the mixing region, merging the two streams and flowing through a third region into a reactor containing immobilized peptides for amino acid addition (see e.g. claim 46).
The difference between ‘952 and the claimed invention is that ‘952 does not claim a deprotection agent or monitoring via UV detectors.
The relevance of ‘947 is set forth above, including use of deprotecting agents and a UV detector.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention that the method of ‘952 could have been modified by including the deprotection process and UV detection of ‘947 in order to provide a process for peptide synthesis. The rationale comes from the general knowledge in the art that solid-phase peptide synthesis requires use of protecting groups to prevent unwanted coupling and that removal of protecting groups after coupling is necessary, such that one of ordinary skill in the art would seek to use such elements and monitor the process via UV detectors. There would have been a reasonable expectation of success because deprotection is a common process in peptide synthesis, as is monitoring via UV detectors. The invention would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
With respect to claims 81-82, the ‘952 art claims carbodiimide and uronium salts as activating agents (see e.g. claim 46).
This is a provisional nonstatutory double patenting rejection.
4. Claims 78 and 80-82 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 72-76, 80, 85, 86, 89, and 90 of copending Application No. 18/523,727 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘727 claims a process that overlaps with the instant claims.
The ’727 application claims a process for adding amino acids to a peptide by merging a stream containing an amino acid and an amino acid activating agent with another stream containing a deprotection agent to a reservoir containing immobilized peptides to achieve amino acid addition to the peptides (see e.g. claim 86). The ‘727 application also claims a system comprising multiple reservoirs, conduits, and a reactor (see e.g. claim 72). The system is also claimed such that the reservoirs contain the reactants used in the process of claim 86 (see e.g. claims 73-76). The system can also include a UV detection system (see e.g. claim 85).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to utilize the system as claimed in ‘727 within the later claimed method, since the system incorporates elements necessary for achieving the process. The rationale comes from the common elements claimed within the system and the process. There would have been a reasonable expectation of success because the elements within the system were known elements necessary to achieve solid-phase peptide synthesis as found in the claimed process. The invention would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
With respect to claims 80-82, the ‘727 application claims alkaline liquids and uronium activating agents (see e.g. claims 89 and 90). The system is also claimed as using carbodiimide as the activating agent (see e.g. claim 80).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ZACHARY J MIKNIS whose telephone number is (571)272-7008. The examiner can normally be reached M-F 9-5.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Melissa Fisher can be reached at (571) 270-7430. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ZACHARY J MIKNIS/Patent Examiner, Art Unit 1658
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