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 .
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.
Withdrawn Objections/Rejections
The objections on paragraphs 2, 120, 167 and 292 of the specification are withdrawn in response to the amendments filed on 04 August 2025.
The objections to the claims are withdrawn in response to the amendments filed on 04 August 2025.
The rejection of claims 141, 143, 147, 149-150, 155, 161 and 163-164 under 112b are withdrawn in response to the amendments filed on 04 August 2025.
Priority
The present application was filed as a proper National Stage (371) entry of PCT Application No. PCT/IL2019/050639, filed 06/05/2019.
Status of the Claims
Claims 140-191 are pending; claims 141-142, 144-145, 147, 149-151, 155-156, 161, 163-165, 169, 173, 175-177, 181, 186 and 188-190 are amended, claims 1-139 are canceled; claims 167-191 are withdrawn. Claims 140-166 are examined below.
Maintained Objection
Specification
The disclosure is objected to because of the following informalities:
In paragraph 260, “can be to reversibly modified” appears to be a typographical error, namely it is suggested that “can be to reversibly modified” read as “can be reversibly modified”.
Appropriate correction is required.
Maintained Rejections
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 142, 144-146, 151, 156 and 165 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.
Claims 142 and 156 recite “…said affinity tag comprises a poly-histidine peptide (6x-His-tag, 10x-His-tag, His-tag), a tetra cysteine peptide (CCPGCC, TC tag)”. It is unclear whether the limitations in the parenthesis are required or merely exemplary.
New Rejection Necessitated by Amendments
Furthermore, regarding claims 142 and 156, it is not clear whether said affinity tag requires both a poly-histidine peptide and a tetra cysteine peptide or only one because there is no “and” or “or” recited between the poly-histidine peptide and tetra cysteine peptide. Therefore, the claims are indefinite.
Claim 144 recites “[t]he system of claim 140140”. It is unclear what “system of claim 140140” is, therefore, the claim is indefinite.
Claim 145 recites “[t]he system of claim 140140”. However, there is no claim 140140. Therefore, the claim is indefinite.
Claim 146 is included in this rejection as it depends from rejected claim 145 but does not clarify the scope of patent protection sought.
New Rejection Necessitated by Amendments
Claims 151 and 165 recite the limitation "a fourth linker". However, it is unclear what “a fourth linker” refers to because a “third linker” is not recited in claims 140, 149-150, 154 or 163-164.
Maintained Rejections
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, 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 140-141, 144-147, 149-151, 153-155, 158-161 and 163-165 are rejected under 35 U.S.C. 103 as being unpatentable over Schwartz et al. (WO 2012071428 A2) ("Schwartz") and Astra Kern et al. (JP 2016531567) ("Astra").
Regarding claims 140 and 154, Schwartz suggests a system (“[t]he present disclosure is directed to methods and/or uses of oligonucleotide conjugates for assays and detections and related systems” Abstract) comprising: a. a recombinant cell (“the sample may comprise…recombinant cells” paragraph 186), b. a first compound comprising a first oligonucleotide (ODN-1) covalently bound to a binder, either directly or through a first linker (“providing a molecular probe, comprising a binding moiety and an oligonucleotide sequence” Abstract, “modified antibodies, modified proteins, or modified peptides may be prepared by attaching at least one moiety comprising a reactive linker capable of conjugating to a modified oligonucleotide. This at least one moiety may be attached by a covalent bond” paragraph 20), said binder comprising affinity to said extracellular binding domain (“The binding moiety may also comprise a specific binding affinity for a target” paragraph 128, “The target may be expressed on the surface of the sample, such as on a membrane, cell-membrane” paragraph 189), and c. a second compound comprising a second oligonucleotide (ODN-2) covalently bound to a synthetic agent, either directly or through a second linker, wherein said second oligonucleotide is complementary to said first oligonucleotide (“providing a detectable component to the sample, wherein the detectable component comprises a signal generating moiety conjugated to an oligonucleotide sequence complementary to the oligonucleotide sequence of the molecular probe” Abstract, “the signal generating moiety may be linked to the oligonucleotide sequence by a covalent attachment” paragraph 184).
Schwartz fails to teach wherein the recombinant cell ectopically expresses a polypeptide, wherein said polypeptide comprises a membranal anchoring domain and an extracellular binding domain.
Astra teaches “multi-part signaling proteins and uses thereof” (Title). Astra further suggests a recombinant cell ectopically expressing a polypeptide, wherein said polypeptide comprises a membranal anchoring domain and an extracellular binding domain (“A non-naturally occurring cell comprising:(a) a first nucleic acid molecule encoding a first fusion protein comprising a first multimerization domain, a hydrophobic domain, and an actuator domain, wherein upon expression of the first fusion protein, the first multimerization domain is localized extracellularly; and (b) a second nucleic acid molecule encoding a second fusion protein comprising a binding domain and a second multimerization domain, wherein the second fusion protein is localized extracellularly upon expression” claim 1 page 10, “The non-naturally occurring cell of any one of the preceding claims, wherein the hydrophobic domain is a transmembrane domain” claim 16, page 12, see Fig. 1B showing the recombinant cell ectopically expressing a polypeptide, wherein said polypeptide comprises a membranal anchoring domain and an extracellular binding domain). Astra further suggests that the recombinant cell is used to treat disease (“The present disclosure relates to compositions and methods for using cellular immunity having fusion protein complexes chemically induced to spatially and temporally control the triggering of cellular signals and downstream responses to treat disease” Abstract, see claim 45).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of Schwartz to rely on the recombinant ectopically expressing a polypeptide, wherein said polypeptide comprises a membranal anchoring domain and an extracellular binding domain taught by Astra because Astra suggests that the recombinant cell treats disease. A person having ordinary skill in the art would have had a reasonable expectation of success because both Schwartz and Astra teach recombinant cells.
Regarding claims 141 and 155, Shwartz further teaches wherein said polypeptide is a cell surface protein (“targets may include… cell surface protein” paragraph 190).
Regarding claim 144 and 158, although the scope of claim 144 is unclear (see 112b rejection above), in the interest of compact prosecution “system of claim 140140” is interpreted as “system of claim 140”. Schwartz further suggests wherein said first linker comprises PEG (“the modified antibody comprises an antibody that has been prepared by attaching at least one moiety comprising a reactive linker capable of conjugating to a modified oligonucleotide. This at least one moiety may be attached by a covalent bond. Furthermore, the at least one moiety may comprise a spacer group, for example, a polymerized ethylene oxide, such as PEG” paragraph 19).
Regarding claims 145-147 and 159-161, although the scope of claim 145 is unclear (see 112b rejection above), in the interest of compact prosecution “system of claim 140140” is interpreted as “system of claim 140”. Schwartz further suggests wherein said first compound further comprises a labeling moiety, wherein said labeling moiety comprises a fluorescent dye, wherein said fluorescent dye is a cyanine dye (“the biomolecule-oligonucleotide conjugates, for example, antibody oligonucleotide conjugates…may comprise one or more detectable fluorophores” paragraph 207, “the probe conjugate is an antibody conjugated to two or three
oligonucleotides…an antibody is joined to a fluorescent dextran” paragraph 135, “An oligonucleotide-biofluor protein…e.g. Cy3…Cy5” paragraph 377).
Regarding claims 149-151 and 163-165, Schwartz suggests wherein said synthetic agent/bioactive moiety of said second compound comprises a fluorescent dye, wherein said dye is coumarin, and wherein said second compound further comprises a second labeling moiety, wherein second labeling moiety is a fluorescent dye, wherein said fluorescent dye is FITC, Boron-Dipyrromethene (“a signal generating moiety may be a fluorophore…the fluorophore may comprise coumarin dyes…FITC…BODIPY” paragraph 183, “In certain embodiments, more than one type of signal generating moiety may be used… by using more than one detectable component, each carrying a different and distinguishable signal generating moiety” paragraph 180).
Regarding claim 153, Schwartz suggests further comprising a third compound comprising a third oligonucleotide (ODN-3), wherein said third oligonucleotide is complementary to said second oligonucleotide (“third panel comprising a plurality of universal adapters, said plurality of universal adapters comprising oligonucleotide sequences having independently paired a plurality of oligonucleotide sequence segments complementary to the plurality of first oligonucleotide sequences and a plurality of oligonucleotide sequence segments complementary to the plurality of second oligonucleotide sequences” paragraph 1029).
Claims 142 and 156 are rejected under 35 U.S.C. 103 as being unpatentable over Schwartz and Astra as applied to claims 141 and 155 above, and further in view of Lata et al. of the American Chemical Society. 2006 Feb 22;128(7):2365-72 (Cite No. 160 of IDS filed 11/29/2021) (“Lata”).
Regarding claims 142 and 156, although the claims are indefinite (see 112b rejection above), in the interest of compact prosecution, the parenthesis are interpreted to be exemplary and not require. Schwartz in view of Astra address claims 141 and 155.
Schwartz in view of Astra fail to teach wherein said transmembranal protein comprises an outer membrane protein C (OmpC); receptor tyrosine kinases (RTKs); Ion channel linked receptors; Enzyme-linked receptors; or G protein-coupled receptors, and/or said affinity tag comprises a poly-histidine peptide (6x-His-tag, 10x-His-tag, His-tag), a tetra cysteine peptide (CCPGCC, TC tag).
Lata teaches “specific and stable fluorescence labeling of histidine-tagged proteins for dissecting multiprotein complex formation” (Title). Lata further teaches wherein said affinity tag comprises a poly-histidine peptide (“Here, we present an efficient method for site-specific and stable noncovalent fluorescence labeling of histidine-tagged proteins… the high selectivity of tris-NTA toward cumulated histidines enabled selective labeling of proteins in cell lysates and on the surface of live cells” Abstract). Lata further suggests that poly-histidine affinity tags enabled the reversibility of a his-tag binder to the his-tag (“[d]espite these high affinities and stabilities of the tris-NTA/oligohistidine complexes, quantitative dissociation within a few seconds was observed upon adding 100Mm imidazole” page 2368 column 2 paragraph 3) which “adds powerful features for the application in fluorescence spectroscopy and microscopy as it enables to in situ remove fluorophores attached to the proteins (e.g., for a control experiment), replenish with fresh fluorophore (e.g., after photobleaching), or exchange against a different fluorophore” (page 2372 column 2 paragraph 1). Lata further suggest that histidine tags are common (“Given the enormous prevalence of the histidine-tag for purification of recombinant proteins” page 2371 column 2 paragraph 1).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of Schwartz in view of Astra to rely on the a poly-histidine affinity tag on the extracellular domain taught by Lata because Lata suggests that this enables reversible binding which adds powerful features in spectroscopy and microscopy. A person having ordinary skill in the art would have had a reasonable expectation of success given that Lata suggests that histidine tags are common in the field of recombinant proteins.
Claims 143 and 157 are rejected under 35 U.S.C. 103 as being unpatentable over Schwartz and Astra as applied to claims 141 and 155 above, and further in view of Nissinkorn et al. Chemistry A European Journal Volume21, Issue45 November 2, 2015 Pages 15981-15987, Cite No. 199 of IDS filed 11/29/2021 ("Nissinkorn").
Regarding claims 143 and 157, Schwartz in view of Astra address claims 141 and 155.
Schwartz in view of Astra fail to teach wherein said His-tag specific binder comprises a moiety represented by the structure of formula E(b) (Applicant’s elected species).
Nissinkorn teaches “sensing protein surfaces with targeted fluorescent receptors” (Title). Nissinkorn further suggests wherein said His-tag specific binder comprises a moiety represented by the structure of formula E(b) (“Figure 2. A method for preparing different protein-surface sensors consisting of a tri-Ni2 + -NTA complex (I)” page 15982). Nissinkorn further teaches that the His-tag binder has high affinity and selectivity to the His-tag protein of interest (“The role of this binder is to ensure that the sensor will bind to the His-tagged POI with high affinity and selectivity (Figure 1, state a)” page 15982 column 1 paragraph 1).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of Schwartz in view of Astra to rely on the His-tag binder of formula E(b) taught by Nissinkorn because Nissinkorn teaches that the His-tag binder of formula E(b) has a high affinity and selectivity to His-tag proteins. A person having ordinary skill in the art would have had a reasonable expectation of success because Nissinkorn shows the structure of the E(b) His-tag binder.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 140-144, 148-158 and 162-166 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-35 of copending Application No. 18/350066 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because:
Regarding claims 140 and 154, copending Application No. 18/350066 recites a system comprising: a. a recombinant cell, or a recombinant cell ectopically expressing a polypeptide, wherein said polypeptide comprises a membranal anchoring domain and an extracellular binding domain, b. a first compound comprising a first oligonucleotide (ODN-1) covalently bound to a binder, either directly or through a first linker, said binder comprising affinity to said extracellular binding domain, and c. a second compound comprising a second oligonucleotide (ODN-2) covalently bound to a synthetic agent/bioactive moiety, either directly or through a second linker, wherein said second oligonucleotide is complementary to said first oligonucleotide (claims 11 and 15).
Regarding claims 141-142 and 155-156, copending Application No. 18/350066 further recites wherein said polypeptide is a cell surface protein (CSP), wherein the system does not perturb said cell's function, wherein said system can be reversibly modified, wherein said recombinant cell is selected from: eukaryotes, prokaryotes, mammalian cells, plant cells, human cells, and bacteria, wherein said membranal anchoring domain comprises a transmembranal protein or a part of it, an artificial polypeptide, or a combination thereof, wherein said binder comprises a His-tag specific binder, said extracellular domain comprises an affinity tag, or any combination thereof, wherein said transmembranal protein comprises an outer membrane protein C (OmpC);receptor tyrosine kinases (RTKs); Ion channel linked receptors; Enzyme-linked receptors; G protein-coupled receptors or any combination thereof, said affinity tag comprises a poly-histidine peptide (6x-His-tag, 10x-His-tag, His-tag), a tetra cysteine peptide (CCPGCC, TC tag) (claims 12-13 and 16).
Regarding claims 143 and 157, copending Application No. 18/350066 further recites wherein said His-tag specific binder comprises a moiety represented by the structure of formula E(b) (Applicant’s elected species) (claim 4)
Regarding claims 144 and 158, copending Application No. 18/350066 further recites wherein said first linker comprises at least one polyethyleneglycol (PEG) moiety, at least one phosphate moiety, at least one thioalkyl moiety or any combination thereof; or said first linker is represented by the following formula: -[(CH2O)k-PO3H]I-(CH2)w-S- wherein k and 1 are each independently an integer number between 0 and 10; and w is an integer number between 1 and 10 (claim 5).
Regarding claims 148 and 162, copending Application No. 18/350066 further recites wherein said first compound is represented by the structure of the nickel complexes of compound 102 (Applicant’s elected species) (claim 7, compound 105).
Regarding claims 149-151 and 163-165, copending Application No. 18/350066 further recites wherein said second oligonucleotide is longer than said first oligonucleotide, comprises a toehold region, or combination thereof, and/or wherein said synthetic agent/bioactive moiety of said second compound is bound to the 3' end or to the 5' end of said second oligonucleotide, and/or wherein said synthetic agent of said second compound comprises a molecular marker, a labeling moiety, a fluorescent dye, an adhesion molecule, a cancer cell binder, a protein binder, a protein ligand, an anticancer agent, a surface binder, a growth factor, an angiogenic factor, a cytokine, a hormone, a DNA molecule, a siRNA molecule, an oligosaccharide, a protein receptor, an immune activator, an immune suppressor, a small molecule, a drug, or a derivative therefore, or any combination thereof, wherein said second compound further comprises a second labeling moiety, and/or, wherein said dye is selected from: dansyl, fluorescein (6-FAM), Fluorescein Amidite--, cyanine dyes (e.g. Cy3, Cy5), sulfoindocyanine, nile red, rhodamine, perylene, fluorenyl, coumarin, 7- methoxycoumarin (Mca), dabcyl, NBD, Nile blue, TAMRA, Boron-Dipyrromethene, FITC or derivative thereof; and/or said protein binder comprises a biotin or a folate; and/or said adhesion molecule comprises a folate; and/or said surface binder is an abiotic surface binder; and/or said surface binder comprises a thiol group (HS), a Si-halogen group, a and/or a Si-O bond; and/or said cancer cell binder comprises a folate; said second labeling moiety is bound to the 3' end or to the 5' end of said second oligonucleotide, directly or through a fourth linker (claims 2-3).
Regarding claims 152 and 166, copending Application No. 18/350066 further recites wherein the second compound is represented by the structure of compound 206 (Applicant’s elected species) (claim 8, compound 207).
Regarding claim 153, copending Application No. 18/350066 further recites further comprising a third compound comprising a third oligonucleotide (ODN-3), wherein said third oligonucleotide is complementary to said second oligonucleotide, and/or wherein said third oligonucleotide comprises higher affinity to said second oligonucleotide than the affinity of said second oligonucleotide to said first oligonucleotide (claim 1).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 145-147 and 159-161 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-35 of copending Application No. 18/350066 in view of Schwartz.
Regarding claims 145-147 and 159-161, copending Application No. 18/350066 fails to recite wherein said first compound further comprises a labeling moiety, wherein said labeling moiety is bound to the 3' end or to the 5' end of said first oligonucleotide, directly or through a third linker, and/or wherein said labeling moiety comprises a fluorescent dye, wherein said fluorescent dye is selected from a group comprising dansyl, fluorescein (6-FAM), Fluorescein Amidite, cyanine dyes (e.g. Cy3, Cy5), sulfoindocyanine, nile red, rhodamine, perylene, fluorenyl, coumarin, 7- methoxycoumarin (Mca), dabcyl, NBD, Nile blue, Tetramethylrhodamine (TAMRA), Boron-Dipyrromethene, Fluorescein Isothiocyanate (FITC) or derivative thereof.
Schwartz suggests wherein said first compound further comprises a labeling moiety, wherein said labeling moiety comprises a fluorescent dye, wherein said fluorescent dye is a cyanine dye (“the biomolecule-oligonucleotide conjugates, for example, antibody oligonucleotide conjugates…may comprise one or more detectable fluorophores” paragraph 207, “the probe conjugate is an antibody conjugated to two or three oligonucleotides…an antibody is joined to a fluorescent dextran” paragraph 135, “An oligonucleotide-biofluor protein…e.g. Cy3…Cy5” paragraph 377). Schwartz further suggests that this increases detection sensitivity (“a hybrid might contain a greater number of detectors linked to each probe, thereby achieving greater sensitivity” paragraph 135).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of , copending Application No. 18/350066 to rely on the first compound further comprising a labeling moiety, wherein said labeling moiety comprises a fluorescent dye, wherein said fluorescent dye is a cyanine dye taught by Schwartz because Schwartz suggests that this increases the detection sensitivity. A person having ordinary skill in the art would have had a reasonable expectation of success because both copending Application No. 18/350066 and Schwartz teach systems comprising complementary oligonucleotides for detection assays.
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
Applicant's arguments filed 8/4/2025 have been fully considered but they are not persuasive.
Regarding the double patenting rejections, Applicant requests that “the rejection [be held] in abeyance until the conflicting claims are allowed” (page 41 para. 8 and page 42 para. 2). However, no claims are allowed.
Regarding the 112b rejections, Applicant argues that “[t]he Examiner further alleged that it is unclear whether the limitations in the parenthesis in claims 142 and 156 are required or merely exemplary. Without acquiescing to the propriety of the rejection, Applicants submit that the limitations in the parenthesis are deleted from these claims” (page 43 para. 1-2). However, the limitations in the parenthesis are not deleted. Applicant further argues that “[t]he Examiner further noted some typos in claims 144 and 145 ( claim 140140) and alleged they render the claims unclear. Without acquiescing to the propriety of the rejection, Applicants submit that the typos are corrected, rendering the rejection moot” (page 43 para. 3-4). However, the typos were not corrected.
Regarding the 103 rejections, Applicant argues that “Schwartz fails to teach that the binder of the first oligonucleotide binding the extracellular binding domain of an ectopically expressed polypeptide” (page 45 para. 3). However, Shwartz suggests that the binder of the first oligonucleotide binds the extracellular binding domain of a recombinant cell because Shwartz teaches that “[t]he binding moiety may also comprise a specific binding affinity for a target” (paragraph 128), and Shwartz further teaches that “[t]he target may be expressed on the surface of the sample, such as on a membrane, cell-membrane” (paragraph 189). Given that Shwartz teaches that “the sample may comprise…recombinant cells” (paragraph 186), Shwartz teaches the claim components of a recombinant cell and a binder to an extracellular binding domain, which reads on the claim limitations, thereby suggesting that the binder of the first oligonucleotide binds the extracellular binding domain of the recombinant cell. Note that the limitation that the extracellular binding domain is an ectopically expressing polypeptide is provided by Astra. Applicant further argues that “Schwartz is even silent regarding an ectopically expressed chimeric polypeptide comprising a binding domain. Paragraph [00186], referenced by the Examiner, merely lists 'recombinant cells' as an example of a sample type, without teaching that the cell expresses the recombinant target polypeptide” (page 45 para. 3). However, as stated above, the limitation of an ectopically expressing polypeptide is provided by Astra. Applicant further argues that “Schwartz not only fails to teach that "the recombinant cell ectopically expresses a polypeptide", as alleged by the Examiner (Office Action, p.9, par. 1), but also, more importantly, that said polypeptide specifically binds ODN-1 binder, as required by claim 140” (page 45 para. 4). However, the Examiner (Office Action, p.9, par. 1) did not allege that Shwartz teaches that "the recombinant cell ectopically expresses a polypeptide". The limitation of an ectopically expressing polypeptide is provided by Astra. Also, as stated above, Shwartz does suggest that the binder of the first oligonucleotide binds the extracellular binding domain of a recombinant cell and by combining Shwartz with Astra, the limitation that said polypeptide specifically binds ODN-1 binder is provided. Applicant further argues that “[t]here is no articulated motivation or teaching in Schwartz that would lead a skilled artisan to modify the system to detect an ectopically expressed, artificial polypeptide, as that of claim 140… Astra addresses a different technical field and problem, and there is no clear rationale why a skilled person would consult Astra to modify Schwartz's detection system” (page 45 para. 5-6). However, Astra does provide motivation to modify the system of Shwartz to detect an ectopically expressed, artificial polypeptide (see rejection above). Applicant further argues that “[w]hile Astra teaches cells ectopically expressing membranal chimeric proteins, it fails to teach or suggest an oligonucleotide bound to a binder comprising affinity to said chimeric proteins. Further, the Office Action does not provide a reasoned explanation as to how or why a skilled artisan would combine Schwartz and Astra, and how the combination would arrive to subject matter within the scope of the claim” (page 46 para. 1). However, as stated above, Shwartz suggest an oligonucleotide bound to a binder comprising affinity to extracellular binding domains of recombinant cells. Shwartz in view of Astra suggest wherein the oligonucleotide bound to the binder comprises affinity to said chimeric proteins. Furthermore, a proper obviousness analysis is made regarding the combination of Schwartz and Astra (see rejection above). Applicant further argues that “[f]rom the above it follows that a combination of Schwartz and Astra fails to teach each and every element of claim 140. Furthermore, the Examiner's rationale appears to be based on hindsight reconstruction of the invention, using the claim as a roadmap, rather than on teachings that would have motivated a skilled artisan to modify Schwartz according to Astra” (page 46 para. 2). However, as stated above, Shwartz in view of Astra teach every element of claim 140 and their combination would have been obvious to a person having ordinary skill in the art with a reasonable expectation of success (see rejection above). Applicant further argues that “even if Lata were further combined with Schwartz and Astra, the resulting combination would still fail to disclose or suggest all features of claim 140” (page 46 para. 5). However, claim 140 is unpatentable over Shwartz and Astra (see rejection above). Applicant further argues that “all elements of claim 140… enable manipulations and functional effects that are neither taught nor contemplated by the prior art… None of these effects are envisioned by Schwartz, Astra, and Late. Accordingly, their combination appears to rely on impermissible hindsight reconstruction rather than on a reasoned motivation found in the prior art” (page 46 last paragraph and page 47 para. 1). However, even if claim 140 enables manipulations and functional effects that are not contemplated by the prior art, claim 140 is still obvious over the prior art for the reasons stated above (see rejection above).
Conclusion
No claim is allowed.
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 FERNANDO IVICH whose telephone number is (703)756-5386. The examiner can normally be reached M-F 9:30-6:00 (E.T.).
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, Gregory S. Emch can be reached at (571) 272-8149. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/Fernando Ivich/ Examiner, Art Unit 1678
/GREGORY S EMCH/Supervisory Patent Examiner, Art Unit 1678