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
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.
Response to Restriction/Election
Applicant’s election with traverse of Group I, claims 1-2, 5-13 and 27, in response to restriction requirement is acknowledged. Applicant’s election without traverse of the following species is also acknowledged:
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, for a single species representing “a nucleoside analog”,
Fluorescently labeled antibody, for a single species representing “binding reagent”, and immunohistochemistry, for a single species representing “identifying and determining”. In the amendments, claims 9-11, 14-23 and 27 have been withdrawn by Applicants.
Applicant’s traversal is on the ground that D1 pertains to measuring samples that come with endogenously labeled proteins, not proteins that have been artificially tagged and, on this basis, all the claims are inventive. Applicant also argued that amended claim 14 is now directed to claim 1 and should be examined together because if claim 1 and/or 13 is patentable, over the prior art, so will be the claims 14 in Group II.
The above arguments have fully been considered but are not found persuasive. First, regarding endogenously labeled protein, the attaching a tag to a protein as recited in the claim, is not limited to tagging only artificially as asserted by applicant and thus attaching a tag endogenously is also included. Moreover, as described in the restriction requirement of 11/18/2025, the special technical feature of protein attached to a tag and identifying the tag by binding to a binding reagent has been found obvious in view of document D1 and D2 and thus the special technical feature does not contribute over the prior art. In regards to claims 14-23, the claims would be grouped into Group II invention if the claim 14 were dependent on claim 13 because claim 14 encompasses distinct method processes and steps involving multiplexing, in vivo administration and distinct detection processes. Restriction for examination purposes as indicated is proper because all the inventions listed in this action are independent or distinct they lack the same corresponding special technical as they do not have a common special technical feature that makes a contribution over the prior art and there would be a serious search and/or examination burden if restriction were not required. Furthermore, the inventions require a different field of search and employing different search queries. Accordingly, non-coextensive searches of the patent and non-patent literature would be necessary. In addition, the inventions are likely to raise different non-prior art issues under 35 U.S.C. 101 and/or 35 U.S.C. 112.
Therefore, claims 9-11, 14-23 and 27 are withdrawn from further consideration as being directed to a non-elected invention. See 37 CFR 1.142(b) and MPEP § 821.03. Applicants preserve their right to file a divisional on the non-elected subject matter.
Status of the claims
Claims 1-2, 5-8 and 12-13 are examined on merits in this office action to the extant it encompasses the elected species.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims claim 5, 12 and 13 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 5 recites “said tag is a nucleoside analog comprising at least one modification compared with a nucleoside of the following formula:
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”. It is unclear as to whether the nucleoside analog is based on the disclosed formula or not because “compared with” is a vague term and it does not clearly indicate that the claimed nucleotide analog is derived from the disclosed structure having at least one modification. Moreover, since the modification has not been clearly described in the claim, the at least one modification encompasses modification on anywhere on the disclosed structure including modification of the furan ring by replacing “O’ with “S” to provide a thiolane ring or deleting a carbon atom of the furan to provide a thietane ring. Are such modifications intended to be encompassed in the claim? Furthermore, R1 is undefined in the claim and thus it is unclear what compounds/moieties are intended for R1 in the claims and so thus the nucleoside analyte which is based on the comparison on the disclosed structure.
Claim 12 is rejected under 35 U.S.C. 112, second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which applicant regards as the invention. Claim 12 provides a method of claim 1, which is a multiplex method. However, since the claim does not set forth any steps involved in the multiplex method/process, it is unclear what method/process applicant is intending to encompass by the recitation “which is a multiplex method”.
Claim 13 is rejected under 35 U.S.C. 112, second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which applicant regards as the invention. Claim 13 provides a method of claim 1, which is a method for tracking a plurality of proteins in vivo. However, since the claim does not set forth any steps involved for the method/process of tracking a plurality of proteins in vivo, it is unclear what method/process applicant is intending to encompass by the recitation “which is a method for tracking a plurality of proteins in vivo”.
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 1-2, 5-8 and 12-13 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.
Claim I is directed to a method of determining location of a protein in a biological sample, comprising: attaching a tag to the protein to form a tagged protein, wherein the tag is a nucleoside or nucleoside analog; contacting the biological sample with the tagged protein; then identifying and determining location of the protein in the sample by contacting the sample with a binding reagent that binds specifically to the tag.
As claimed the nucleoside analog encompasses inordinately a large number of different types of analogs and the detection process requires various types of binding reagent each specifically directed to a single analog out of the inordinately a large number of analogs. The binding reagent encompasses various types of binding reagents, as for example, nucleic acid, lectin, specific binding compounds and antibody. If antibody is considered, the process encompasses inordinately a large number of distinct antibodies each directed to a single species of an analog out of the various types of nucleoside analogs. As claimed in claim 5, the nucleoside analog
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encompasses various distinct analogs. As for example, the at least one modification encompasses modification on anywhere on the disclosed structure including modification of the furan ring by replacing “O’ with “S” to provide a thiolane ring or deleting a carbon atom of the furan to provide a thietane ring. The at least one modification includes modification by attaching various types of molecules/compound anywhere on the above nucleoside including attaching the molecules to 3’ hydroxyl, 5’ hydroxyl and to R1 wherein the molecules/compound for the modification includes various distinct molecules, as for example, proteins, nucleic acid, fluorophores, saccharides and various types of molecules. Thus depending of the modified structure, the process includes various types of distinct antibodies directed to each of the various types of modified nucleoside.
However, throughout the specification, clear description and disclosure is very limited to one type of nucleoside analog and the binding reagent is strictly limited to antibody directed to the one type of analog. In the specification, the only nucleoside analog structure disclosed is
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(Fig. 1; Note that in the structure, the ribose sugar structure is different, modified by replace the oxygen moiety with a CH2 moiety in the ring structure) and the disclosed binding reagent is limited to antibody wherein the antibody disclosed is very limited to antibody against 3’-azidomethyl-deoxyadenine, 3’-azidomethyl-deoxycytosine, 3’-azidodimethyl-deoxyguanine and 3’-azidomethyl-deoxythiamine (paragraph [0086]).
Therefore, by disclosing only of a few antibodies against nucleoside analogs where in all the analogs hydrogen of 3’ hydroxyl group is replaced with azidomethyl group for R1 is dA, dT, dG and dC, the specification does not clearly describe representative examples and description of the various types of nucleoside analogs and various types of binding agents and various distinct species of antibody directed to the various types of nucleoside analog as encompassed by the claims.
"[A] sufficient description of a genus ... requires the disclosure of 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" (AbbVie, 759 F.3d at 1297, reiterating Eli Lilly, 119 F.3d at 1568-69) (emphasis added). Recently, the U.S. Court of Appeals for the Federal Circuit (Federal Circuit) decided Amgen v. Sanofi, 872 F.3d 1367 (Fed. Cir. 2017), which concerned adequate written description for claims drawn to antibodies. Amgen v. Sanofi describes how when an antibody is claimed, 35 U.S.C. § 112(a) requires adequate written description of the antibody itself; not just a description of the sequence to which the antibody binds. Amgen, 872 F.3d at 1378-79. Office guidance has been updated to reflect that adequate written description of a newly characterized antigen alone should not be considered adequate written description of a claimed antibody to that newly characterized antigen (i.e., 2-hydroxyisobutyrylated lysine), even when preparation of such an antibody is routine and conventional. MPEP § 2163 states that, for a claimed genus, the written description requirement 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:
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. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (Claims directed to a functionally defined genus of antibodies were not supported by a disclosure that “only describe[d] one type of structurally similar antibodies” that “are not representative of the full variety or scope of the genus.”). The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure “indicates that the patentee has invented species sufficient to constitute the gen[us].” See Enzo Biochem, 323 F.3d at 966, 63 USPQ2d at 1615; Noelle v. Lederman, 355 F.3d 1343, 1350, 69 USPQ2d 1508, 1514 (Fed. Cir. 2004) (Fed. Cir. 2004) (“[A] patentee of a biotechnological invention cannot necessarily claim a genus after only describing a limited number of species because there may be unpredictability in the results obtained from species other than those specifically enumerated.”). “A patentee will not be deemed to have invented species sufficient to constitute the genus by virtue of having disclosed a single species when … the evidence indicates ordinary artisans could not predict the operability in the invention of any species other than the one disclosed.” In re Curtis, 354 F.3d 1347, 1358, 69 USPQ2d 1274, 1282 (Fed. Cir. 2004).
Emphasis added.
Consequently, by disclosing only a few species of nucleoside analogs and only a few species on antibody directed against few specific species of nucleoside structures where in all the analogs hydrogen of 3’ hydroxyl group is replaced with azidomethyl group for R1 is dA, dT, dG and dC, the claims do not provides representative support for the large number of distinct nucleosides and distinct antibodies as encompassed by the claims and accordingly, the claims do not meet the written description provision of 35 USC 112(pre-AIA ), first paragraph.
Claim Rejections - 35 USC § 103
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 of this title, 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.
Claims 1-3 and 6 are rejected under 35 U.S.C. 103 as obvious over Alexander et al. (WO 2017/079763A1; Cite # 11 in the IDS filed 5/11/23) in view of Drmanac et al (WO 2018129214A1; Cite # 12 in the IDS filed 5/11/23).
Alexander discloses a method for generating representative data comprising analyzing the homogenate composition. Said homogenate composition derived from a heterogeneous tissue sample comprising substantially homogeneously distributed cellular structures, wherein a ratio of cellular structures in each subset of the homogenate is substantially similar to the ratio of cellular structures in the tissue sample. The analyzing comprises generating quantitative and/or qualitative data for a marker in the homogenate composition. The marker may comprise a protein, which comprises a modification selected from a group consisting of covalent attachment of a nucleotide or a nucleotide derivative (tag). The marker is measured by flow cytometry, immunohistochemistry staining (claims 119-126). Therefore, Alexander teaches detection of marker protein modified with nucleotide or nucleotide derivative in the homogenate.
Claim 1 differs from the reference of Alexander in that the reference does not disclose identifying and determining location of the protein by contacting the sample with a binding reagent that binds specifically to the tag.
Drmanac discloses a method for detecting incorporation of a reversible terminator deoxyribonucleotide at the 3' end of a primer extension product, wherein the reversible terminator deoxyribonucleotide comprises a nucleobase, a sugar moiety, and a cleavable blocking group, said method comprising (a) combining
(i) the primer extension product including the incorporated reversible terminator deoxyribonucleotide, and
(ii) a first affinity reagent that binds to the incorporated reversible terminator deoxyribonucleotide, wherein the first affinity reagent binds to the nucleobase, the cleavable blocking group, or both, and(b) detecting binding of the first affinity reagent to the incorporated reversible terminator deoxyribonucleotide. The nucleobase is a nucleobase analog. The first affinity reagent is an antibody. The first affinity reagent is conjugated to or bound to a detectable label, and detecting binding of the affinity reagent to the incorporated reversible terminator deoxyribonucleotide in step (b) comprises detecting a signal from the detectable label (claims 1,7,16,17). Thus, Drmanac discloses nucleoabase as detectable/tag moiety detectable by binding to a reagent (an antibody) that binds specifically to the deoxyribonucleotide and detecting binding of the affinity reagent to deoxyribonucleotide comprising detecting a signal from the detectable label.
Therefore, from the description in mind of Alexander and Drmanac, it is obvious to one of ordinary skilled in the art to consider the nucleotide analog of Drmanac for the nucleotide or nucleotide derivative of Alexander with the expectation of providing Alexander for covalently attaching a nucleotide analog for immunoassay detection with an labeled antibody to identify and determine location of the tagged marker protein in Alexander with a reasonable expectation of success. One of ordinary skilled in the art would be motivated to utilize the nucleotide analog of Drmanac because Drmanac discloses NHS activated nucleotide analog (see Fig.9) useful for covalently linking to an amine group of a protein and because Alexander teaches modification selected from a group consisting of covalent attachment of a nucleotide or a nucleotide derivative. One of ordinary skilled in the art would also be motivated to utilize the nucleotide analog of Drmanac because Drmanac teaches affinity reagent (antibody) specific for the nucleobase wherein the antibody is conjugated to a detectable label for detection ([0078]).
In regards to claims 2, 5 and 6, Drmanac discloses nucleoside analog
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, which reads on the nucleoside analogs as claimed in claim 2, 5 and 6.
In regards to claim 7, as described above, Drmanac teaches binding agent (antibody) comprising a detectable label for detection ([0078]) wherein the detectable label is a fluorescent label (para [0037], [0013]).
In regards to claim 8, Alexander, as described above, teaches immunohistochemistry staining and Drmanac teaches detection includes excitation and detection by fluorescence spectroscopy (para [0026]; claims 21, 35).
In regards to claims 12 and 13, since the basic concept is obvious by the prior arts, different variations of detection, including multiplexing and detecting plurality of proteins by labeling different nucleoside analogs would be obvious to one of ordinary skilled in the art. Moreover, Drmanac teaches multiplexing comprising labeling plurality of DNA molecules with plurality of different nucleoside analogs (claims 60 & 61) and utilizing plurality of affinity reagents directed to the plurality of nucleoside analogs (claim 61) and one of ordinary skilled in the art can easily envisage multiplexing of detection of plurality of marker proteins similarly by attaching to plurality of nucleoside analogs in view of Drmanac.
Conclusion
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/SHAFIQUL HAQ/Primary Examiner, Art Unit 1678