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 .
Claim Status and Formal Matters
This action is in response to papers filed 2/24/2026.
Claims 36-55 are pending.
Claim 36 has been amended.
Applicant's election with traverse of group 1, claims 36-38, " the immobilization oligonucleotide or the nucleic acid molecule is attached directly to the support; " the capture oligonucleotide is attached directly to the support, and " the capture oligonucleotide is configured to hybridize the nucleic acid sequence of the nucleic acid molecule when in complex with the target molecule to capture the nucleic acid molecule-target molecule complex. in the reply filed on 5/17/2024 is acknowledged. The traversal is on the ground(s) that ,” Specifically, the claimed apparatus is configured to allow displacement and re-capture of nucleic of nucleic acid molecules when a target molecule is present in a sample. O’Meara relates to an apparatus which is configured in a different way and is not suitable for carrying out the displacement and re-capture assay of the present invention.” This is not found persuasive because as the probes of O’Meara are nucleic acids. Nucleic acids allow for displacement and recapture based on hybridization conditions. Thus the argument is not persuasive.
Claims 39-55 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected inventions, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 5/17/2024.
Clams 36-38 are being examined.
The previous objection to the specification has been withdrawn in view of the amendment.
Priority
The instant application was filed 02/22/2021 and is a national stage entry of PCT/GB2019/052361 with an international filing date: 08/22/2019 and claims foreign priority to UK1813789.3, filed 08/23/2018.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Claim Interpretation
The following is a quotation of 35 U.S.C. 112(f):
(f) Element in Claim for a Combination. – An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The following is a quotation of pre-AIA 35 U.S.C. 112, sixth paragraph:
An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art. The broadest reasonable interpretation of a claim element (also commonly referred to as a claim limitation) is limited by the description in the specification when 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is invoked.
As explained in MPEP § 2181, subsection I, claim limitations that meet the following three-prong test will be interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph:
(A) the claim limitation uses the term “means” or “step” or a term used as a substitute for “means” that is a generic placeholder (also called a nonce term or a non-structural term having no specific structural meaning) for performing the claimed function;
(B) the term “means” or “step” or the generic placeholder is modified by functional language, typically, but not always linked by the transition word “for” (e.g., “means for”) or another linking word or phrase, such as “configured to” or “so that”; and
(C) the term “means” or “step” or the generic placeholder is not modified by sufficient structure, material, or acts for performing the claimed function.
Use of the word “means” (or “step”) in a claim with functional language creates a rebuttable presumption that the claim limitation is to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites sufficient structure, material, or acts to entirely perform the recited function.
Absence of the word “means” (or “step”) in a claim creates a rebuttable presumption that the claim limitation is not to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is not interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites function without reciting sufficient structure, material or acts to entirely perform the recited function.
Claim limitations in this application that use the word “means” (or “step”) are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action. Conversely, claim limitations in this application that do not use the word “means” (or “step”) are not being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action.
This application includes one or more claim limitations that use the word “means” or “step” but are nonetheless not being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph because the claim limitation(s) recite(s) sufficient structure, materials, or acts to entirely perform the recited function. Such claim limitation(s) is/are: “detection means” in claim 37.
Because this/these claim limitation(s) is/are not being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, it/they is/are not being interpreted to cover only the corresponding structure, material, or acts described in the specification as performing the claimed function, and equivalents thereof.
If applicant intends to have this/these limitation(s) interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, applicant may: (1) amend the claim limitation(s) to remove the structure, materials, or acts that performs the claimed function; or (2) present a sufficient showing that the claim limitation(s) does/do not recite sufficient structure, materials, or acts to perform the claimed function.
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 36-38 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.
As set forth in In re Alonso 88 USPQ2d 1849 (Fed. Cir. 2008), at 1851:
The written description requirement of 35 U.S.C. § 112, ¶ 1, is straightforward: “The specification shall contain a written description of the invention ….” To satisfy this requirement, the specification must describe the invention in sufficient detail so “that one skilled in the art can clearly conclude that the inventor invented the claimed invention as of the filing date sought.” Lockwood v. Am. Airlines, Inc., 107 F.3d 1565, 1572 [41 USPQ2d 1961] (Fed. Cir. 1997); see also LizardTech, Inc. v. Earth Res. Mapping, Inc., 424 F.3d 1336, 1345 [76 USPQ2d 1724] (Fed. Cir. 2005); Eiselstein v. Frank, 52 F.3d 1035, 1039 [34 USPQ2d 1467] (Fed. Cir. 1995).
Alonso at 1852:
A genus can be described by disclosing: (1) a representative number of species in that genus; or (2) its “relevant identifying characteristics,” such as “complete or partial structure, other physical and/or chemical properties, functional characteristics when coupled with a known or disclosed correlation between function and structure, or some combination of such characteristics.” Enzo, 323 F.3d at 964.
In applying the test as set forth in Alonso, the independent claim is drawn to an apparatus for detecting the presence, absence or level of a target small molecule in a sample, comprising: a) a first region comprising: i) a support, ii) an immobilisation oligonucleotide attached directly or indirectly to the support and comprising SEQ ID NO: 2, and iii) a DNA aptamer comprising a sequence that is reverse complementary to SEQ ID NO: 2,wherein: SEQ ID NO: 2 and the sequence that is reverse complementary to SEQ ID NO: 2 oligonucleotide attached directly or indirectly to the support and comprising SEQ ID NO: 3 and/or SEQ ID NO: 4,wherein:the aptamer further comprises a sequence that is reverse complementary to SEQ ID NO: 3 and/or SEQ ID NO: 4, and wherein SEQ ID NO: 3 and the sequence that is reverse complementary to SEQ ID NO: 3 and/or SEQ ID NO: 4 and the sequence that is reverse complementary to SEQ ID NO: 4 enable hybridization between the aptamer and the capture oligonucleotide when the aptamer is in complex with the target small molecule; and wherein the presence or level of the target small molecule is detected..
Thus the claims encompass any apparatus with any first region on any support with any aptamer with a sequence that is reverse complementary to SEQ ID NO :2 and an immobilization oligonucleotide SEQ ID NO 2 and a further region comprising a support and capture oligonucleotide SEQ ID NO 3 or SEQ ID NO 4. The aptamer must be at least partially complementary to the immobilization oligonucleotide, which encompasses a single nucleotide to completely complementary. Further the wherein the aptamer is capable of being displaced from the immobilisation oligonucleotide by undergoing a conformational change leading to the release of the aptamer from the duplex structure if the small molecule is present in the sample, wherein the aptamer is capable of binding to the small molecule through a mechanism which is independent of Watson-Crick base pairing.
The claims further require anything that can broadly be interpreted as a second region with a capture oligonucleotide that is attached to a support and allows hybridization between the aptamer and capture oligonucleotide comprising SEQ ID NO 3 and/or SEQ ID NO 4. The nucleic acid must be at least partially complementary to the capture oligonucleotide, which encompasses a single nucleotide to completely complementary.
The specification on page 1 states, “Aptamers are small artificial ligands, including single stranded DNA, RNA or polypeptide molecules which are capable of binding to specific target moieties of interest with high affinity and specificity. Aptamers are regarded as alternatives to antibodies for use as diagnostic agents and/or therapeutic agents.” The specification on page 8 states, “n certain embodiments, the nucleic acid molecule is an aptamer. Aptly, the aptamer is selected from a double-stranded aptamer, a single-stranded aptamer and an aptamer which is double-stranded over at least a portion of its length.” The specification teaches, “As used herein, "nucleic acid molecule" and "aptamer," are used interchangeably to refer to a non-naturally occurring nucleic acid molecule that has a desirable action on a target molecule.10 For nucleic acid tamers, for example, a distinction is made between DNA aptamers formed from single-stranded DNA (ssDNA) and RNA aptamers formed from single-stranded RNA (ssRNA). Aptamers can show high binding property to the target molecule, and the affinity thereof is often high compared to antibodies having a similar function. Aptamers are characterized by the formation of a specific three-dimensional structure that depends on the nucleic acid sequence. The three-dimensional structure of an aptamer arises due to Watson and Crick intramolecular base pairing, Hoogsteen base pairing (quadruplex), wobble pair formation or other non-canonical base interactions. This structure enables aptamers, analogous to antigen-antibody binding, to bind target structures accurately. A particular nucleic acid sequence of an aptamer may, under defined conditions, have a three-dimensional structure that is specific to a defined target structure. The nucleic acid aptamers described herein may comprise natural or non-natural nucleotides and/or or base derivatives (or combinations thereof). In certain embodiments, the nucleic acid molecule comprises one or more modifications such that it comprises a chemical structure other than deoxyribose, ribose, phosphate, adenine (A), guanine (G), cytosine (C), thymine (T), or uracil (U). The nucleic acid molecule may be modified at the nucleobase, at the pentose or at the phosphate backbone. “ (page 15).
The specification teaches on page 20, “The term "target molecule" as used herein denotes a molecule which may be found in a tested sample and which is capable of binding to a nucleic acid molecule described herein. In accordance with some embodiments, the target molecule is an organic molecule. In some embodiments, the target molecule is a soluble antigen, a cell-surface antigen, or an antigen associated with a micelle, a liposome or a particle. In one embodiment, the target molecule is an antigen. In some embodiments, the target molecule may be a protein, a polypeptide, a peptide, a ganglioside, a lipid, a phospholipid, a carbohydrate, a small molecule or a nucleic acid molecule. In certain embodiments, a soluble antigen may be a protein, a peptide, an enzyme, a cytokine, a soluble cancer marker, an inflammation-associated marker, a hormone and/or a soluble molecule derived from a virus, bacteria or a fungus for example, a toxin or an allergen. In some embodiments, the antigen is a micro-organism associated antigen. As used herein, the term "micro-organism associated antigen" is to be understood as a protein or fragment thereof encoded by the viral, bacterial or fungal genome. In certain embodiments, the antigen is a cancer (or tumour) marker. In general, a tumour marker may be found in the body fluids such as in blood or urine, or in body tissues. Tumour markers may be expressed or over expressed in cancer and are generally indicative of a particular disease process.”” This is an enormous genus of target molecules as it encompasses any organic molecule, soluble antigen, a cell-surface antigen, or an antigen associated with a micelle, a liposome or a particle protein, a peptide, an enzyme, a cytokine, a soluble cancer marker, an inflammation-associated marker, a hormone and/or a soluble molecule derived from a virus, bacteria or a fungus for example, a toxin or an allergen.
The specification teaches the nucleic acid molecule can be an aptamer.
While the claims encompass an enormous genus of aptamers, artificial ligands, including single stranded DNA, RNA or polypeptide molecules which are capable of binding to small molecule with high affinity and specificity, which have affinity or desirable effect on target molecules.
The claim further requires the functional requirements of “wherein the aptamer is capable of being displaced from the immobilisation oligonucleotide by undergoing a conformational change leading to the release of the aptamer from the duplex structure if the small molecule is present in the sample, wherein the aptamer is capable of binding to the small molecule through a mechanism which is independent of Watson-Crick base pairing” and “wherein :the aptamer further comprises a sequence that is reverse complementary to SEQ ID NO: 3 and/or SEQ ID NO: 4, and wherein SEQ ID NO: 3 and the sequence that is reverse complementary to SEQ ID NO: 3 and/or SEQ ID NO: 4 and the sequence that is reverse complementary to SEQ ID NO: 4 enable hybridization between the aptamer and the capture oligonucleotide when the aptamer is in complex with the target small molecule; and wherein the presence or level of the target small molecule is detected.”
The teachings of the specification are to a single nucleic acid sequence encompassing an aptamer (SEQ ID NO 2.). Thus while the claims encompass a large genus of target small molecules the teachings of the specification are limited to two.
Ruddigkeit (| J. Chem. Inf. Model. 2012, 52, 2864−2875) teaches there were 166 billion organic small molecules in 2012)
While the claims require ““wherein the aptamer is capable of being displaced from the immobilisation oligonucleotide by undergoing a conformational change leading to the release of the aptamer from the duplex structure if the small molecule is present in the sample, wherein the aptamer is capable of binding to the small molecule through a mechanism which is independent of Watson-Crick base pairing” and “wherein: the aptamer further comprises a sequence that is reverse complementary to SEQ ID NO: 3 and/or SEQ ID NO: 4, and wherein SEQ ID NO: 3 and the sequence that is reverse complementary to SEQ ID NO: 3 and/or SEQ ID NO: 4 and the sequence that is reverse complementary to SEQ ID NO: 4 enable hybridization between the aptamer and the capture oligonucleotide when the aptamer is in complex with the target small molecule; and wherein the presence or level of the target small molecule is detected.”
The teachings of the specification are limited to aptamers in which binding causes release from revFOR and REV and are rebound to the same revFOR and REV with the target intact which is confusing as if the binding of the target causes release, what is removed or added to allow recapture. In example 2 the target eluted material is hybridized to revFOR for determination.
Thus while the claims encompass the aptamers with affinity for any small target molecule in any sample from any species by any DNA aptamer with a binding affinity for any small molecule.
The specification provides only two species of the genus of aptamers, only 2 species of immobilization and capture oligonucleotides. Thus the claims lack adequate written description of is aptamers of DNA, RNA or polypeptide;.
Response to Arguments
The response begins traversing the rejection by citing court decisions the representative views as pertain it. This is noted.
Th response continues by asserting the amendments address the issues. This argument has been thoroughly reviewed but is not considered persuasive as the claims encompass at least 166 billion small molecules, but the specification only provides possession for two of the enormous genus.
Further the claims require “wherein the aptamer is capable of being displaced from the immobilisation oligonucleotide by undergoing a conformational change leading to the release of the aptamer from the duplex structure if the small molecule is present in the sample, wherein the aptamer is capable of binding to the small molecule through a mechanism which is independent of Watson-Crick base pairing” and “wherein:the aptamer further comprises a sequence that is reverse complementary to SEQ ID NO: 3 and/or SEQ ID NO: 4, and wherein SEQ ID NO: 3 and the sequence that is reverse complementary to SEQ ID NO: 3 and/or SEQ ID NO: 4 and the sequence that is reverse complementary to SEQ ID NO: 4 enable hybridization between the aptamer and the capture oligonucleotide when the aptamer is in complex with the target small molecule; and wherein the presence or level of the target small molecule is detected.” The specification provides no structure function relationship to demonstrate possession.
The response continues by providing where the specification provides antecedent basis for different limitations of the claims. This is noted, however the cited portions do not provide a structure function relationship to demonstrate possession of “wherein the aptamer is capable of being displaced from the immobilisation oligonucleotide by undergoing a conformational change leading to the release of the aptamer from the duplex structure if the small molecule is present in the sample, wherein the aptamer is capable of binding to the small molecule through a mechanism which is independent of Watson-Crick base pairing” and “wherein:the aptamer further comprises a sequence that is reverse complementary to SEQ ID NO: 3 and/or SEQ ID NO: 4, and wherein SEQ ID NO: 3 and the sequence that is reverse complementary to SEQ ID NO: 3 and/or SEQ ID NO: 4 and the sequence that is reverse complementary to SEQ ID NO: 4 enable hybridization between the aptamer and the capture oligonucleotide when the aptamer is in complex with the target small molecule; and wherein the presence or level of the target small molecule is detected.”
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 35-38 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 36 has been amended to recite, “wherein the aptamer is capable of being displaced from the immobilisation oligonucleotide by undergoing a conformational change leading to the release of the aptamer from the duplex structure if the small molecule is present in the sample,.” The recitation of “the aptamer is capable of being displaced from the immobilisation oligonucleotide by undergoing a conformational change leading to the release of the aptamer from the duplex structure if the small molecule is present in the sample” suggest there is also “the aptamer is incapable of being displaced from the immobilisation oligonucleotide by undergoing a conformational change leading to the release of the aptamer from the duplex structure if the small molecule is present in the sample.” The specification and claims provide no standard how to differentiate the aptamer is capable of being displaced from the immobilisation oligonucleotide by undergoing a conformational change leading to the release of the aptamer from the duplex structure if the small molecule is present in the sample from the aptamer is incapable of being displaced from the immobilisation oligonucleotide by undergoing a conformational change leading to the release of the aptamer from the duplex structure if the small molecule is present in the sample. Thus the metes and bounds are unclear.
Further claim 36 recites, “wherein the aptamer is capable of binding to the small molecule through a mechanism which is independent of Watson-Crick base pairing.” The recitation of “wherein the aptamer is capable of binding to the small molecule through a mechanism which is independent of Watson-Crick base pairing” suggests “wherein the aptamer is incapable of binding to the small molecule through a mechanism which is independent of Watson-Crick base pairing.”
Response to Arguments
The previous rejection has been withdrawn in view of the amendment. However the amendment necessitated a new ground of rejection.
Summary
No claims are allowed.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 STEVEN C POHNERT PhD whose telephone number is (571)272-3803. The examiner can normally be reached Monday- Friday about 6:00 AM-5:00 PM, every second Friday off.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Anne Gussow can be reached at (571)272-6047. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Steven Pohnert/Primary Examiner, Art Unit 1683
