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 .
DETAILED ACTION
This Office Action is a response to Applicant’s Election filed June 1, 2026.
Claims 1-21 are pending in the present application.
Election/Restrictions
Applicant’s election (with traverse) of Group I in the reply filed on June 1, 2026 is acknowledged. Applicant’s traversal is twofold.
The first traversal is on the grounds that Applicants request that the restriction requirement be reconsidered because the Examiner has not shown that a serious burden would result if all the claims are examined together. In particular, any search for a synthetic aptamer comprising a bispecific recognition domain targeting at least two cell surface receptors of Group I, would necessarily be a search for methods of using said synthetic aptamers of Group II and Group III. For at least these reasons, Applicants submit that Group II and Group III should be rejoined with elected Group I.
Applicant’s second traversal regards the election of species, and submits that there are a reasonable number of species claimed and the six synthetic aptamers represents a finite number of species and thus, Applicants should not be required to elect a species when Applicants have not claimed an unreasonable number of species.
Applicant’s traversals have been fully considered by the Examiner and they are found persuasive (in-part). Concerning the first traversal, as detailed in the Requirement for Restriction/Election filed May 6, 2026, there would be a serious burden on the Examiner if restriction were not required because the three Grouped inventions require a different field of search since the inventions have acquired a separate status in the art in view of their different classification; the inventions have acquired a separate status in the art due to their recognized divergent subject matter; the inventions require a different field of search (for example, searching different classes/subclasses or electronic resources, or employing different search queries); and the inventions are likely to raise different non-prior art issues under 35 U.S.C. 101 and/or 35 U.S.C. 112, first paragraph. The restriction requirement between the three Grouped inventions is therefore deemed proper.
Applicant is reminded that if the elected invention (e.g. product claim) is found allowable, withdrawn process claims that depend from or otherwise include all the limitations of the allowable product claim will be rejoined in accordance with the provisions of MPEP § 821.04.
Regarding the second traversal, the Examiner has found Applicant’s arguments persuasive. Therefore, the six synthetic aptamers recited in the claims will be searched and examined together.
Accordingly, claims 14-21 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.
The requirement is still deemed proper and is therefore made FINAL.
Claims 1-13 have been examined on the merits as detailed below:
Information Disclosure Statement
Applicant’s information disclosure statement (IDS) filed April 7, 2025 is acknowledged. The submission is in compliance with the provisions of 37 CFR §1.97. Accordingly, the Examiner has considered the information disclosure statement, and a signed copy is enclosed herewith.
Drawings
The Drawings filed December 4, 2023 are objected to because Figs. 3A-3C, 8B-8D and 9A-9E of the instant application lack eligible features due to pixelation. In addition, the Y- and X-axis of those Figures cannot be determined. 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 Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 6-12 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a written description rejection.
The following quotation from section 2163 of the Manual of Patent Examination Procedure is a brief discussion of what is required in a specification to satisfy the 35 U.S.C. 112 written description requirement for a generic claim covering several distinct inventions:
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice..., reduction to drawings..., or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus... See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
A "representative number of species" means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.
Thus, when a claim covers a genus of inventions, the disclosure must provide written support for the entire scope of the genus. Support for a genus is generally found where the Applicant has provided a number of examples sufficient so that one in the art would recognize from the specification the scope of what is being claimed and that applicant was in possession of the claimed genus.
The instant claims are drawn to a synthetic aptamer comprising a bispecific recognition domain targeting at least two cell surface receptors, wherein the synthetic aptamer comprises a nucleic acid sequence with at least 50% sequence identity to SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, or SEQ ID NO: 6. The present Specification discloses:
As used herein, “bispecific recognition” refers to the ability of a macromolecule (i.e. DNA, RNA, polypeptide, proteins, or antibodies) to simultaneously recognize and/or bind two different antigens, or target molecules
There is insufficient written description of the synthetic aptamer encompassed by the claims. The present Specification discloses a synthetic aptamer comprising a bispecific recognition domain targeting at least two cell surface receptors, wherein the synthetic aptamer comprises SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, or SEQ ID NO: 6, but does not describe sequences with any percent identity that function as claimed to simultaneously recognize and/or bind two different antigens, or target molecules.
Written description requirement for claims that recite a synthetic aptamer comprising a bispecific recognition domain targeting at least two cell surface receptors, wherein the synthetic aptamer comprises SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, or SEQ ID NO: 6 with the percent sequence identities that function as claimed to simultaneously recognize and/or bind two different antigens, or target molecules is not met because the Specification does not provide any description of any variants or what sequences could be modified (added, deleted or mutated) that retain function. Accordingly, the claims encompass using a genus of synthetic aptamer comprising a bispecific recognition domain targeting at least two cell surface receptors which are not adequately described. The claims are rejected because there is insufficient description of the genus of synthetic aptamers encompassed by the claims.
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed.” (See page 1117.) The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116). It is noted that conception is not achieved until reduction to practice has occurred regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016.
To satisfy the written description requirement an applicant must describe the invention is such a way as to convey to one skilled in the art that applicant had the invention in his possession when the application was filed. Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1351 (Fed. Cir. 2010) (en banc). In cases such as the instant application where a genus is claimed, the specification must contain “either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can ‘visualize or recognize’ the members of the genus.” Id. at 1350. However, written description requirement for claims that recite a synthetic aptamer comprising a bispecific recognition domain targeting at least two cell surface receptors, wherein the synthetic aptamer comprises SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, or SEQ ID NO: 6 with the percent sequence identities that function as claimed to simultaneously recognize and/or bind two different antigens, or target molecules is not met.
The entire genus of synthetic aptamer comprising a bispecific recognition domain targeting at least two cell surface receptors, wherein the synthetic aptamer comprises SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, or SEQ ID NO: 6 with the percent sequence identities that function as claimed to simultaneously recognize and/or bind two different antigens, or target molecules as claimed does not exist in the instant application. That is, adequate written description support does not exist to practice the full scope of the invention claimed. The specification nor the art discloses neither a representative number of species compounds nor any structure/function correlation that would enable one of skill to immediately envision the genus synthetic aptamers required to practice the full scope of the invention.
As stated above, the MPEP states that written description for a genus can be achieved by a representative number of species within a broad generic claim. Given the breadth of the claims, the Specification lacks sufficient variety of species to reflect the variance in the genus.
In conclusion, the Specification and the prior art as filed does not provide sufficient descriptive support for the myriad of synthetic aptamers embraced by the claims. For the reasons discussed above, the 35 USC § 112 rejection for written description is applicable.
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 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.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 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 –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim 1, 2, 4 and 13 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Du et al. (Biomater. Sci., Published on 10 May 2021, 9, 4159-4168).
The claims are drawn to a synthetic aptamer comprising a bispecific recognition domain targeting at least two cell surface receptors.
Du et al. disclose a synthetic aptamer comprising a bispecific recognition domain targeting immune checkpoint surface receptors, CTLA-4 and PD-L1. See P1/C4 bi-apt, which was composed of CTLA-4 aptamer and PD-L1 aptamer, with an auxiliary sequence at their junction to form a gapped double-stranded structure. Its 5′-end is modified with phosphate and the 3′-end is modified with hydroxyl, which can form a stable circular structure through the action of T4 DNA ligase. The bispecific aptamer was mixed with T4 DNA ligase buffer which represents a pharmaceutically acceptable carrier.
Therefore, Du et al. anticipate claims 1, 2, 4 and 13.
Claim Rejections - 35 USC § 103
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.
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 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 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 obviousness or nonobviousness.
Claims 1 and 5 are rejected under 35 U.S.C. 103 as being unpatentable over Du et al. (Biomater. Sci., Published on 10 May 2021, 9, 4159-4168) in view of Odeh et al. Molecules 2020, 25, 3: pages 1-51).
The claims are drawn to a synthetic aptamer comprising a bispecific recognition domain targeting at least two cell surface receptors, wherein the synthetic aptamer comprises one or more deoxyuridine (dU) nucleotides.
Du et al. is relied upon as discussed above.
Du et al. do not teach wherein the synthetic aptamer comprises one or more deoxyuridine (dU) nucleotides.
Odeh et al. teach chemical modification of aptamers for increased binding affinity in diagnostic applications. Odeh et al. particularly teach that aptamers comprising dU nucleotides exhibit improved stability against nucleases and increased binding affinity.
Before the effective filing date of the claimed invention, a synthetic aptamer comprising a bispecific recognition domain targeting at least two cell surface receptors was known in the prior art of Du et al.
A person of ordinary skill in the art would have been motivated and expected reasonable success to modify the bi-specific aptamer of Du et al. to include one or more dU nucleotides as taught and suggested by Odeh et al. for the purpose of improving stability against nucleases and increasing binding affinity.
Therefore, the subject matter of claims 1 and 5 is obvious over Du et al. in view of Odeh et al.
Art Made of Record but not Relied Upon
Ayass et al. (Cancers 2024, 16, 1041, pages 1-41, plus Supplementary Materials and Figures) is art made of record but not relied upon. Ayass et al. teach a dual checkpoint aptamer targeting CTLA-4 and NKG2A/CD94 heterodimer for the purpose of unleashing both T and NK cells and enhancing CD8+ T and NK cell functions for tumor cell lysis.
Conclusion
Claim 3 is objected to as being dependent upon a rejected base claim but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Any inquiry concerning this communication or earlier communications from the Examiner should be directed to Terra C. Gibbs whose telephone number is 571-272-0758. The Examiner can normally be reached from 8 am - 5 pm M-F.
If attempts to reach the Examiner by telephone are unsuccessful, the Examiner's supervisor, Ram Shukla can be reached on 571-272-0735. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
Patent applicants with problems or questions regarding electronic images that can be viewed in the Patent Application Information Retrieval system (PAIR) can now contact the USPTO's Patent Electronic Business Center (Patent EBC) for assistance. Representatives are available to answer your questions daily from 6 am to midnight (EST). The toll free number is (866) 217-9197. When calling please have your application serial or patent number, the type of document you are having an image problem with, the number of pages and the specific nature of the problem. The Patent Electronic Business Center will notify applicants of the resolution of the problem within 5-7 business days. Applicants can also check PAIR to confirm that the problem has been corrected. The USPTO's Patent Electronic Business Center is a complete service center supporting all patent business on the Internet. The USPTO's PAIR system provides Internet-based access to patent application status and history information. It also enables applicants to view the scanned images of their own application file folder(s) as well as general patent information available to the public.
For all other customer support, please call the USPTO Call Center (UCC) at 800-786-9199.
/TERRA C GIBBS/Primary Examiner, Art Unit 1635
Prosecution Insights