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
Applicant’s amendments and remarks filed on June 24, 2026 are acknowledged. Claims 1, 9, 12, and 13 were amended. Claims 1-14 are pending and are examined on the merits herein.
It is noted that the amendment to the claims filed on June 24, 2026 does not comply with the requirements of 37 CFR 1.121(c) because the status identifier for claim 13 indicates that the claim is previously presented but the claim contains markings and should indicate that it is currently amended. However, in the interest of compact prosecution, the amendment to the claims has been entered.
Priority
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Withdrawn Objections
In view of Applicant’s amendments and response, the objections to the drawings and claims 9 and 12 are withdrawn.
Withdrawn Rejections
In view of Applicant’s amendments and response, the 35 U.S.C 112(b) rejection is withdrawn.
Drawings
The drawings were received on June 24, 2026. These drawings are found acceptable by the examiner.
Specification
It is noted that the amendment to the specification filed on June 24, 2026 does not comply with the requirements of 37 CFR 1.121(b) because the full text of the replacement paragraphs on pages 1, 3, 8, 22, 24, and 32 are not shown relative to the immediate prior version of the paragraph. Therefore, the Examiner is maintaining the objections to the specification.
The disclosure is objected to because of the following informalities:
Page 5: a period is missing at the end of the following paragraph:
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Page 8: Description of Figure 2 reads in part “middle und bottom” and should read “middle and bottom” (emphasis added).
Appropriate correction is required.
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01. See e.g., pages 1, 2, 3, 4, 11, 27, and 32.
Response to Arguments
Applicant's arguments filed June 24, 2026 have been fully considered but they are not persuasive.
It is noted that the amendment to the specification filed on June 24, 2026 does not comply with the requirements of 37 CFR 1.121(b) because the full text of the replacement paragraphs on pages 1, 3, 8, 22, 24, and 32 are not shown relative to the immediate prior version of the paragraph.
Specifically, the amended paragraph on page 1 reads in part “have ben confirmed” and should read “have been confirmed” (emphasis added) because the word “been” is now misspelled. In addition, the amended paragraph on page 3, line 9 reads in part “Zoa et al.” and “Diagnostic”, but should read “Zou et al.” and “Diagnostics”. The amended paragraph on page 3, line 32 reads in part “it ahs become apparent” and “Carerj”, but should read “it has become apparent” and “Carerj ML”. The amended paragraph on page 8 reads in part “positions in the upper spectrum” but should read “position in the upper spectrum”. The amended paragraph on page 22 reads in part “as targe amino acids” and should read “as target amino acids” because the word “target” is now misspelled. The amended paragraph on page 24 reads in part “databases” and should read “database” and the “Journal of Chemical Information and Modeling” is not italicized but should be in italics. Lastly, the amended paragraph on 32 reads in part “PLOS ONE” but should be in italics and the last word in the paragraph reads in part “GPCR-AABs” but should read “GPCR-fAABs”. Therefore, the Examiner is maintaining the objections to the specification.
Claim Rejections - 35 USC § 112
New Grounds of Rejections Necessitated by Amendment
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 7-10 and 14 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 1 was amended and recites in part “comprising SEQ ID No. 1” and thus is interpreted as requiring the entire sequence of SEQ ID NO: 1. Claims 7 and 9 (reproduced below) depend on claim 1 and recite in part “comprises a nucleic acid sequence of SEQ ID No. 1”. The limitation “a nucleic acid sequence of SEQ ID No. 1” is given its broadest reasonable interpretation which is two or more consecutive nucleotides of SEQ ID NO: 1 and thus does not require the entire sequence of SEQ ID NO: 1. Claims 8 and 10 (reproduced below) depend on claims 7 and 9 respectively and recite in part “consists of a nucleic acid sequence of SEQ ID No. 1”. The limitation “consists of a nucleic acid sequence of SEQ ID No. 1” is interpreted as only consisting of a fragment of two or more consecutive nucleotides of SEQ ID NO: 1 and thus does not require the entire sequence of SEQ ID NO: 1. Therefore, claims 7-10 do not include all of the limitations of the claim from which it depends on.
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Claim 13 was amended and recites in part “comprising SEQ ID No. 1” and thus is interpreted as requiring the entire sequence of SEQ ID NO: 1. Claim 14 depends on claim 13 and recites in part “comprises the nucleic acid sequence of SEQ ID No. 1”. Therefore, claim 14 is the same scope as claim 13 and does not further limit the claim which it depends on.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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.
Written Description
Claims 7-10 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.
Claims 7 and 9 are drawn to the provision of a genus of aptamers comprising a nucleic acid sequence of SEQ ID NO: 1. In this context, the phrase “a nucleic acid sequence of SEQ ID NO: 1” is given its broadest reasonable interpretation, which is two or more consecutive nucleotides of SEQ ID NO: 1 and thus does not require the entire sequence of SEQ ID NO: 1. Claims 8 and 10 are drawn to the provision of a genus of aptamers consisting of a nucleic acid sequence of SEQ ID NO: 1. In this context, the phrase “consisting of a nucleic acid sequence of SEQ ID NO: 1” is interpreted as requiring only consisting of a fragment of two or more consecutive nucleotides of SEQ ID NO: 1. Moreover, the claims do not limit the target to which the recited aptamer may bind. The specification defines the term “aptamer” as an oligonucleotide that binds specifically and with high affinity to a target molecule [page 13, fourth paragraph]. Thus, the claims encompass a broad genus of aptamers that comprises any fragment of SEQ ID NO: 1 or consists of any fragment of SEQ ID NO: 1 defined solely by function to bind specifically and with high affinity to a target molecule.
To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of a complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, and any combination thereof.
The specification discloses the following:
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[page 6].
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[page 13].
Working example 2 discloses that the aptamer BC 007 of SEQ ID NO: 1 demonstrated highly efficient inhibition of virus replication at low doses in Vero as well as Calu-3 cell lines. Specifically, the half-maximal effective concentrations (EC50, alternatively termed half-maximal inhibitory concentration IC50) determined for inhibition of viral infection were 3.74 µM for Calu-3 cells and 0.21 µM for Vero cells. The specification also discloses that for comparison purposes, several other antiviral agents implicated for potential treatment of SARS-CoV-2 as disclosed in Wang et al. (Cell Research 2020) were tested in a similar experimental setup using Vero E6 cells. Specifically, the specification discloses that Wang et al. taught that the EC50 concentration for remdesivir was 0.77 µM. Based on the results obtained with remdesivir, it was concluded that remdesivir potently blocked virus infection at low micromolar concentration and lacked substantial cell toxicity at the concentrations used for testing its SARS-CoV-2 inhibiting effect. Therefore, in view of the results reported in Wang et al., the specification discloses that the results obtained in Vero cells with the aptamer of the present invention also demonstrates potent blockage of virus infection up to or even beyond the efficiency observed with other antiviral agents currently discussed as potential treatment options for Coronaviridae infections.
Working example 6 discloses characterization of GPCR-AAB activity in long COVID-19 serum samples before and after administration of aptamer BC007 (SEQ ID NO: 1). Specifically, the working example demonstrated that GPCR autoantibodies which were found and identified in patients having overcome COVID-19 and suffering from symptoms persisting after infection and being associated with long COVID have direct and measurable effects on G-protein coupled receptors. Further, the specification discloses that it could clearly be demonstrated that administration of BC007 to long COVID patients was able to counteract the effects of said GPCR autoantibodies presumably by specific binding and persistent neutralization of such autoantibodies. The data represents experimental evidence that BC007 is able to neutralize GPCR autoantibodies appearing as one of the main causative agents of long COVID after an infection with SARS-CoV-2 has been overcome.
Even if one accepts that the examples described in the specification meet the claim limitations of the rejected claims with regard to structure and function, the examples are only representative of aptamers consisting of the nucleic acid sequence of SEQ ID NO: 1. The results are not necessarily predictive of other aptamers falling within the broadly claimed genus. Thus, it is impossible for one to extrapolate from the limited examples described herein those aptamers that would necessarily meet the structural/functional characteristics of the rejected claims.
The prior art does not appear to offset the deficiencies of the instant specification in that it does not describe a set of aptamers comprising a nucleic acid sequence of SEQ ID NO: 1 or aptamers consisting of a nucleic acid sequence of SEQ ID NO: 1 that could result in binding specifically and with high affinity to a target molecule.
Therefore, the skilled artisan would have reasonably concluded applicants were not in possession of the claimed invention for claims 7-10.
Response to Arguments
Applicant's arguments filed June 24, 2026 have been fully considered but they are not persuasive.
Applicant asserts that the claim amendments overcome the 35 U.S.C. 112(a) written description rejection.
This argument is not found persuasive. Applicant did not amend the dependent claims to be consistent with the amendment to the independent claim. Specifically, dependent claims 7-10 as currently written encompass a broad genus of aptamers that comprises any fragment of SEQ ID NO: 1 (claims 7 and 9) or consists of any fragment of SEQ ID NO: 1 (claims 8 and 10) defined solely by function to bind specifically and with high affinity to a target molecule.
Enablement
Claims 1-12 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 enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the
enablement requirement and whether any necessary experimentation is "undue". These factors include, but are not limited to: (A) The breadth of the claims; (B) The nature of the invention; (C) The state of the prior art; (D) The level of one of ordinary skill; (E) The level of predictability in the art; (F) The amount of direction provided by the inventor; (G) The existence of working examples; and (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure. All of the Wands factors have been considered with regard to the instant claims, with the most relevant factors discussed below.
Breadth of claims:
Claim 1 is drawn to a method of treating long COVID in a subject having overcome an infection with a virus from the Coronaviridae family comprising administering to a subject in need thereof an effective amount of an aptamer comprising SEQ ID NO: 1. The broadest reasonable interpretation of claim 1 is a method of treating long COVID in a subject having overcome an infection with any virus from the Coronaviridae family comprising administering to a subject in need thereof an effective amount of an aptamer comprising SEQ ID NO: 1.
Nature of the invention:
The specification as filed envisions that the aptamers are useful for the treatment of infections with virus strains from the Coronaviridae family in human and animal subjects [page 17, last paragraph]. The specification also envisions the aptamer for use in therapy of a subject by treating, curing, or preventing disease symptoms associated with long COVID in a patient having overcome an infection with a virus from the Coronaviridae family wherein the aptamer comprises a nucleic acid sequence of SEQ ID NO: 1 and/or a nucleic acid sequence being at least 80% identical to SEQ ID NO: 1 [page 18, fifth paragraph]. The specification discloses that long COVID is a condition or a complex of symptoms which has been observed in patients which have overcome an infection with a virus from the Coronaviridae family. While the complex of symptoms associated therewith is still under examination, it becomes more and more evident that symptoms prevail even after disappearance of symptoms of an active infection [page 18, last full paragraph].
Amount of direction provided by the inventor and existence of working
examples:
Working example 2 discloses that the aptamer BC 007 of SEQ ID NO: 1 demonstrated highly efficient inhibition of virus replication at low doses in Vero as well as Calu-3 cell lines. Specifically, the half-maximal effective concentrations (EC50, alternatively termed half-maximal inhibitory concentration IC50) determined for inhibition of viral infection were 3.74 µM for Calu-3 cells and 0.21 µM for Vero cells. The specification also discloses that for comparison purposes, several other antiviral agents implicated for potential treatment of SARS-CoV-2 as disclosed in Wang et al. (Cell Research 2020) were tested in a similar experimental setup using Vero E6 cells. Specifically, the specification discloses that Wang et al. taught that the EC50 concentration for remdesivir was 0.77 µM. Based on the results obtained with remdesivir, it was concluded that remdesivir potently blocked virus infection at low micromolar concentration and lacked substantial cell toxicity at the concentrations used for testing its SARS-CoV-2 inhibiting effect. Therefore, in view of the results reported in Wang et al., the specification discloses that the results obtained in Vero cells with the aptamer of the present invention also demonstrates potent blockage of virus infection up to or even beyond the efficiency observed with other antiviral agents currently discussed as potential treatment options for Coronaviridae infections.
Working example 5 discloses the identification and characterization of GPCR autoantibodies in sera of patients having recovered from active SARS-CoV-2 infections.
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Working example 6 discloses characterization of GPCR-AAB activity in long COVID-19 serum samples before and after administration of aptamer BC007 (SEQ ID NO: 1). Specifically, the working example demonstrated that GPCR autoantibodies which were found and identified in patients having overcome COVID-19 and suffering from symptoms persisting after infection and being associated with long COVID have direct and measurable effects on G-protein coupled receptors. Further, the specification discloses that it could clearly be demonstrated that administration of BC007 to long COVID patients was able to counteract the effects of said GPCR autoantibodies presumably by specific binding and persistent neutralization of such autoantibodies. The data represents experimental evidence that BC007 is able to neutralize GPCR autoantibodies appearing as one of the main causative agents of long COVID after an infection with SARS-CoV-2 has been overcome.
State of the prior art, level of predictability in the art, and level of one of
ordinary skill:
A review of the prior art shows that the state of the art of treating long COVID in a subject having overcome an infection with a virus from the Coronaviridae family comprising administering to a subject in need thereof an effective amount of an aptamer comprising SEQ ID NO: 1 is immature and nascent.
Quantity of experimentation:
In view of the breadth of the claims which embrace treating long COVID in a subject having overcome an infection with any virus from the Coronaviridae family comprising administering to a subject in need thereof an effective amount of an aptamer comprising SEQ ID NO: 1, the state and level of predictability in the art, the lack of working examples to show treatment of long COVID in a subject having overcome an infection with any virus from the Coronaviridae family, and the failure to provide adequate guidance to overcome the state and level of predictability of the art, one of skill would have to perform undue experimentation in order to practice the invention commensurate in scope with the claims.
Response to Arguments
Applicant's arguments filed June 24, 2026 have been fully considered but they are not persuasive.
Applicant asserts that the claim amendments overcome the 35 U.S.C. 112(a) enablement rejection.
This argument is not found persuasive. The claims as currently written still embrace treating long COVID in a subject having overcome an infection with any virus from the Coronaviridae family comprising administering to a subject in need thereof an effective amount of an aptamer comprising SEQ ID NO: 1. As discussed in the original 35 U.S.C. 112(a) enablement rejection, in view of the breadth of the claims which embrace treating long COVID in a subject having overcome an infection with any virus from the Coronaviridae family comprising administering to a subject in need thereof an effective amount of an aptamer comprising SEQ ID NO: 1, the state and level of predictability in the art, the lack of working examples to show treatment of long COVID in a subject having overcome an infection with any virus from the Coronaviridae family, and the failure to provide adequate guidance to overcome the state and level of predictability of the art, one of skill would have to perform undue experimentation in order to practice the invention commensurate in scope with the claims. Therefore, the Examiner is maintaining the 35 U.S.C. 112(a) enablement rejection.
Claim Rejections - 35 USC § 102
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 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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 13 and 14 are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by Schimke et al. (US 9,234,201).
Regarding claim 13, the clause “for treating long COVID in a subject having overcome an infection with a virus from the Coronaviridae family” is the preamble and is interpreted as intended use of the invention while the body of the claim sets forth all the limitations.
Regarding claims 13 and 14, Schimke et al. teaches an aptamer comprising or consisting of the nucleic acid sequence of SEQ ID NO: 1 for use in therapy and/or diagnosis of autoimmune diseases [abstract]. Schimke et al. teaches a pharmaceutical composition comprising at least one aptamer and optionally at least one pharmaceutically acceptable excipient [column 6, second full paragraph]. Schimke et al. SEQ ID NO: 1 (designated as Db) has a 100% match to instant SEQ ID NO: 1 (designated as Qy) as shown in the alignment below.
Query Match 100.0%; Score 15; DB 1; Length 15;
Best Local Similarity 100.0%;
Matches 15; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 GGTTGGTGTGGTTGG 15
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Db 1 GGTTGGTGTGGTTGG 15
Response to Arguments
Applicant's arguments filed June 24, 2026 have been fully considered but they are not persuasive.
Applicant asserts that claims 13 and 14 are rejected under 35 U.S.C. § 103 as being anticipated by U.S. Patent No. 9,234,201 to Schimke et al. Applicant also asserts the following:
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These arguments are not found persuasive. As an initial matter, claims 13 and 14 are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by Schimke et al. (US 9,234,201) not 35 U.S.C. § 103. Nonetheless, the clause in claim 13 “for treating long COVID in a subject having overcome an infection with a virus from the Coronaviridae family” is the preamble and is interpreted as intended use of the invention while the body of the claim sets forth all the limitations. Therefore, Schimke et al. still meets the limitations of claims 13 and 14 as currently written and stand rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2).
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHRISTINA TRAN whose telephone number is (571)270-0550. The examiner can normally be reached M-F 7:30 - 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, Jennifer Dunston can be reached at (571) 272-2916. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/C.T./
Examiner, Art Unit 1637
/Jennifer Dunston/Supervisory Patent Examiner, Art Unit 1637
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