DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Status of the Application
Claims 1-5, 8-12 and 15-19 are pending and under current examination.
Claim Rejections - 35 USC § 102 (b)
The following is a quotation of the appropriate paragraphs of pre-AIA 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(b) the invention was patented or described in a printed publication in this or a foreign country or in public use or on sale in this country, more than one year prior to the date of application for patent in the United States.
Claims 1-4, 8, 10-12, 15 and 17-19 are rejected under the pre-AIA 35 U.S.C. 102(a) as being anticipated by Wada (WO2010/064146 A2; published on 06/10/2010).
Wada discloses process of making chirally controlled oligonucleotide as well as nucleic acids (greater than 15 nucleotide) in 5’-3’ or 3’-5’ direction with examples comprising steps of coupling using chiral N-cyanomethylpyrrolidinium triflate to make stereochemically pure phosphoramidite (same as in the instant claims 2 and 3), using at least one such phosphoramidite, capping (amino of auxillary chiral moiety and 5’OH by blocking), modifying, deblocking and repeating steps until a desired length is achieved using in at least one step a coupling partner phosphoramidite, (same as in the instant claims 2 and 3), wherein at least one cycle of the steps forms a phosphorothioate diester linkage (same as in the instant claim 1), and a internucleotidic linkage, with L as bond and R1 as alkyl (same as formula I-c of the instant claims) with examples with most examples wherein Ba is thymidine (entire application, especially, abstract, claims, 0020-0033, 0057, 00130, 0179-0184, 0187-0190, 0199, 0205, 00213, 0263-270, 00299-00301, 00319, 00328-00336, 358, 376, 377, 0432-0467, 561, 628). Wada further discloses nucleobases, nucleosides, capping of the amino group in the chiral auxillary and capping of unreacted 5’OH and deblocking comprising use of acid (entire application, especially, abstract, claims, 0020-0033, 0057, 00130, 0179-0184, 0187-0190, 0199, 0205, 00213, 0263-0270, 00299-00301, 00319, 00328, 00328-00336, 0358-0370, 376, 377, 0432-0467, 561, 0624-0628 and 0644-0646 (scheme 19 with base thymidine, thus reads on Claims 2, 3 and 4)).
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Paragraphs 00299-00301 discloses that reaction comprises the step of reacting with an electrophile (oxidation step) in modification step, such as alkyl thiol. Paragraphs 00360-00375 discloses that different nucleoside, nucleotide with modified bases, sugars or phosphate group may be used in making oligonucleotide.
Since the cited prior art reads on all the limitations of the instant claims 1-4, 8, 10-12, 15 and 17-19 these claims are anticipated.
Claim Rejections - 35 USC § 103
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained through the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under the pre-AIA 35 U.S.C. 103(a) 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 obviousnessor nonobviousness.
Claim(s) 1-5, 8, 10-12, 15 and 17-19 are rejected under the pre-AIA 35 U.S.C. 103(a) as being unpatentable over by Wada (WO2010/064146 A2; published on 06/10/2010) in view of Seela (Helvetica Chimica Acta, Vol71, 1988, pages 1813-1823).
Application Claims
Applicant claims a process of making chirally controlled oligonucleotide.
Determination of the scope and contents of the prior art
Wada discloses process of making chirally controlled oligonucleotide as well as nucleic acids (greater than 15 nucleotide) in 5’-3’ or 3’-5’ direction with examples comprising steps of coupling using chiral N-cyanomethylpyrrolidinium triflate to make stereochemically pure phosphoramidite (same as in the instant claims 2 and 3), using at least one such phosphoramidite, capping (amino of auxillary chiral moiety and 5’OH by blocking), modifying, deblocking and repeating steps until a desired length is achieved using in at least one step a coupling partner phosphoramidite, (same as in the instant claims 2 and 3), wherein at least one cycle of the steps forms a phosphorothioate diester linkage (same as in the instant claim 1), and a internucleotidic linkage, with L as bond and R1 as alkyl (same as formula I-c of the instant claims) with examples with most examples wherein Ba is thymidine (entire application, especially, abstract, claims, 0020-0033, 0057, 00130, 0179-0184, 0187-0190, 0199, 0205, 00213, 0263-270, 00299-00301, 00319, 00328-00336, 358, 376, 377, 0432-0467, 561, 628). Wada further discloses nucleobases, nucleosides, capping of the amino group in the chiral auxillary and capping of unreacted 5’OH and deblocking comprising use of acid (entire application, especially, abstract, claims, 0020-0033, 0057, 00130, 0179-0184, 0187-0190, 0199, 0205, 00213, 0263-0270, 00299-00301, 00319, 00328, 00328-00336, 0358-0370, 376, 377, 0432-0467, 561, 0624-0628 and 0644-0646 (scheme 19 with base thymidine, thus reads on Claims 2, 3 and 4)).
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Paragraphs 00299-00301 discloses that reaction comprises the step of reacting with an electrophile (oxidation step) in modification step, such as alkyl thiol. Paragraphs 00360-00375 discloses that different nucleoside, nucleotide with modified bases, sugars or phosphate group may be used in making oligonucleotide.
Ascertainment of the differences between the prior art and the claims
The differences between Wada and the instant claim is:
Instant claim 5 has a limitation wherein phosphoramidite of formula:
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is used in making oligonucleotide.
With regard to the above difference- Although the cited prior art is silent about giving example of specific phosphoramidite of claim 5 in making oligonucleotide, Wada teaches that known modified nucleobases, nucleotides etc., may be used in making oligonucleotides. Thus, it would have been prima facie obvious to a person of ordinary skill in the art to use known modified nucleotides, nucleobases etc. in making oligonucleotides, such as taught by Seela (Helvetica Chimica Acta, Vol71, 1988, pages 1813-1823).
In the same field of endeavor of making oligonucleotides, Seela teaches a method of making oligonucleotide using cyanoethyl phosphoramidite (entire article, especially page 1816):
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Thus, with the guidance provided by Wada and Seela it would have been prima facie obvious to a person of ordinary skill in the art with a reasonable expectation of success that cyanoethyl phosphoramidite may also be incorporated in making chirally controlled oligonucleotide
Therefore, the instant claims would have been obvious to one of ordinary skill in the art.
Finding of prima facie obviousness rational and motivation
(MPEP 2142-2143)
To establish a prima facie case of obviousness, rationales that may support a conclusion of obviousness include:
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(A) Combining prior art elements according to known methods to yield predictable results;
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(B) Simple substitution of one known element for another to obtain predictable results;
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(C) Use of known technique to improve similar devices (methods, or products) in the same way;
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(D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results;
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(E) “Obvious to try” – choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success;
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(F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art;
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(G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention; and (MPEP § 2143).
In this case, Wada teaches a method of making chirally controlled oligonucleotide using protected phosphoramidite, including chiral phosphoramidite and other phosphoramidite Seela teaches cyanoethyl phosphoramidite in making oligonucleotide.
Thus, with the guidance provided by Wada and Seela it would have been prima facie obvious to a person of ordinary skill in the art with a reasonable expectation of success that cyanoethyl phosphoramidite may also be incorporated in making chirally controlled oligonucleotide
Thus, the instantly claimed process would have been prima facie obvious to one of ordinary skill in the art in view of combined teachings of Wada and Seela.
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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1-5, 8-12 and 15-19 in the instant application are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 10590413 B2; and claims 1-20 of U.S. Patent No. 11643657 B2, since the claims, if allowed, would improperly extend the “right to exclude" already granted in the patent.
Although the conflicting claims are not identical, they are not patentably distinct from each other because of the following reasons:
The claims of instant application and claims 1-20 of U.S. Patent No. 10590413 B2; and claims 1-20 of U.S. Patent No. 11643657 B2 are drawn to a process of making same product using same reactant, and steps with a difference in wording.
The difference of wording, however, does not constitute a patentable distinction, because the claims in the present invention simply fall within the scope of claims 1-20 of U.S. Patent No. 10590413 B2; and claims 1-20 of U.S. Patent No. 11643657 B2. For the foregoing reasons, the instantly claimed process is made obvious.
Furthermore, there is no apparent reason why applicant was prevented from presenting claims corresponding to those of the instant application during prosecution of the application which matured into a patent. See also MPEP § 804.
Response to Arguments
Applicant’s remarks and amendment, as filed on 10/20/2025, have been fully considered but not found persuasive.
Applicant argued over rejection under 102b and 103 that the cited prior art 9a scheme only teaches modification but not further coupling, scheme 6 only teaches compound with P=O and H instead of S-L-R1 of the instant claims. Applicant argued that in scheme 19, oligonucleotide is not drawn out for coupling and P=O is bonded to S, BH3 or NR1R2 anions and not used for coupling
This is not found persuasive and the instant claims stand rejected. This is because Wada discloses process of making chirally controlled oligonucleotide as well as nucleic acids (greater than 15 nucleotide) in 5’-3’ or 3’-5’ direction with examples comprising steps of coupling using chiral N-cyanomethylpyrrolidinium triflate to make stereochemically pure phosphoramidite (same as in the instant claims 2 and 3), using at least one such phosphoramidite, capping (amino of auxillary chiral moiety and 5’OH by blocking), modifying, deblocking and repeating steps until a desired length is achieved using in at least one step a coupling partner phosphoramidite, (same as in the instant claims 2 and 3), wherein at least one cycle of the steps forms a phosphorothioate diester linkage (same as in the instant claim 1), and a internucleotidic linkage, with L as bond and R1 as alkyl (same as formula I-c of the instant claims) with examples with most examples wherein Ba is thymidine (entire application, especially, abstract, claims, 0020-0033, 0057, 00130, 0179-0184, 0187-0190, 0199, 0205, 00213, 0263-270, 00299-00301, 00319, 00328-00336, 358, 376, 377, 0432-0467, 561, 628). Wada further discloses nucleobases, nucleosides, capping of the amino group in the chiral auxillary and capping of unreacted 5’OH and deblocking comprising use of acid (entire application, especially, abstract, claims, 0020-0033, 0057, 00130, 0179-0184, 0187-0190, 0199, 0205, 00213, 0263-0270, 00299-00301, 00319, 00328, 00328-00336, 0358-0370, 376, 377, 0432-0467, 561, 0624-0628 and 0644-0646 (scheme 19 with base thymidine, thus reads on Claims 2, 3 and 4)).
Applicant is separating individual steps (reaction scheme) to argue over them individually that separately steps of the cited prior art are not teaching the steps of the instant claims. Applicant further at convenience picks up some steps while leave other steps and teachings of the prior art to argue that the steps are not taught by the cited prior art. Contrary to applicant’s argument, the rejection was made on every teaching of the cited prior art and all the schemes recited in the office action and not individual steps or schemes that applicant pick and selected for argument. The cited prior art specifically provided teaching to make oligonucleotides using steps of coupling, capping, modifying, deblocking and repeating steps and with scheme reciting such steps. Even if scheme 9a is a specifically a modification step, the instant claims also recite a modification step without distinguishing what steps may qualify as modification. In modification step of 9a, the cited prior teaches
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modification of phosphate group attached to an oligonucleotide with a thiol group, wherein L is a bond and R1 is H, alkyl, alkenyl, alkynyl or aryl group (all read on S-L-R1) of the instant claims.
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The cited prior at further teaches using oligonucleotide and elongating it and repeating steps till desired oligonucleotide is obtained. The cited prior art elaborates on every step coupling, capping, modifying, deblocking and repeating steps with discussion on what chemicals to use, how to perform each step. Scheme 19 provides another alternative for such modification, wherein phosphoramidite with S-L-R is made separately for coupling in the oligonucleotide and then elongating such oligonucleotide. Thus, the prior art elaborate teaching of each individual step, two alternative ways to include formula I-c, in the oligonucleotide and elongating through coupling---repeating steps.
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Applicant argued over ODP rejection that absence of any improper extension of the right to exclude over the cited reference patents there should not be any nonstatutory double patenting.
This is not found persuasive and the instant claims stand rejected under ODP. This is because reason for ODP rejection is not just to prevent improper extension “right to exclude” but also to prevent the possibility of multiple suits against an accused infringer by different assignees of patents claiming patentably indistinct variations of the same invention.
The doctrine of nonstatutory double patenting also seeks to prevent the possibility of multiple suits against an accused infringer by different assignees of patents claiming patentably indistinct variations of the same invention. In re Van Ornum, 686 F.2d 937, 944-48, 214 USPQ 761, 767-70 (CCPA 1982) (citing Chisum, Patents, § 9.04(2)(b) (1981)). A terminal disclaimer, submitted in compliance with 37 CFR 1.321(c) or (d) to overcome a double patenting rejection, includes a provision that the patent or any patent issuing from the application is only enforceable for and during such period that it is owned by the same party (or parties) that owns the other patents or applications, identified in the terminal disclaimer, that claim obvious variations of one invention. Van Ornum, 686 F.2d at 944-45, 214 USPQ at 767 (citing Chisum, Patents, § 9.04(2)(b) (1981)).
Conclusion
No Claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PANCHAM BAKSHI whose telephone number is (571)270-3463. The examiner can normally be reached M-Thu 7-4.30 EST.
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/PANCHAM BAKSHI/Primary Examiner, Art Unit 1623