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 6/23/2025
Claims 1, 6, have amended.
Claims 38-41 have been added by amendment.
Applicant’s election without traverse of Group I, in the reply filed on - the first target molecule is directly bound to a first optical label; - the second target molecule is indirectly bound to a first optical label; the first target molecule and the second target molecule are optically distinguishable in one or more color channels by virtue of (b) different intensities of similar color between the first optical label and the second optical label; - the first optical label and the second optical label have peak emission wavelengths separated by <100 nm.is acknowledged.
The species with respect to direct or indirect labeling has been withdrawn.
Claims 7-15,17, 26-28 withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species or inventions, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 7/14/2023.
Claims 1, 6, 16, 38- 41are being examined.
Priority
The instant application was filed 09/10/2021 and claims priority from provisional application 63077119 , filed 09/11/2020.
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 1, 6, 16, 38- 41 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 1 has been amended to recite, “A biological sample prepared for examination, comprising: a first target molecule bound, directly or indirectly, to a first plurality of probes each attached with a first optical label and a third optical label, a second target molecule bound, directly or indirectly, to a second plurality of probes each attached with a second optical label and a fourth optical label (a) the first and the second target molecules are nucleic acids or proteins, a second a target molecule bound, directly or indirect, to a second plurality of probes each attached with a second optical label and fourth optical label , (b) the first the second optical labels have the same or overlapping color spectra but different intensities (c)the third and fourth optical labels have the same or overlapping emission spectra but different intensities, (d) the first and the second target molecules are optically distinguishable by comparing (i) a first intensity ratio of the first and the third optical labels associated with the first target molecule and (ii) a second intensity ratio of the second and the fourth optical labels associated with the second target molecule..” Thus the claims encompass any first, second, third, and fourth optical labels. The specification teaches, “The specification teaches, “0064] The term "optical label" or simply "label" refers to a molecule or a biological moiety which, upon suitable excitation, can emit signals detectable by optical means. Examples include fluorescent dyes (such as Cy3, Cy5, Alexa 532), fluorescent proteins (such as GFP, YFP and RFP) chromogenic dyes, quantum dots and other kinds of nanoparticles. In some embodiments, the optical label is reactive and can be attached to another molecule, such as a probe. Examples include Hydroxycoumarin, Aminocoumarin, Methoxycoumarin, Cascade Blue, Pacific Blue, Pacific Orange, Lucifer yellow, NBD , R-Phycoerythrin (PE), PE-Cy5 conjugates, PE-Cy7 conjugates, Red 613, PerCP , TruRed, FluorX , Fluorescein, BODIPY-FL, G-Dye100, G-Dye200, G-Dye300, G-Dye400, Cy2, Cy3, Cy3B, Cy3.5, Cy5, Cy5.5, Cy7, TRITC, X-Rhodamine, Lissamine Rhodamine B, Texas Red, Allophycocyanin (APC), and APC-Cy7 conjugates. In some embodiments, the optical labels are photoswitchable dyes, such as photoswitchable rodamine amides. In some embodiments, optical labels are attached onto probes by chemical conjugation. In some embodiments, optical labels are attached onto probes by physical association only but not chemical reaction. In some embodiments, optical labels are attached onto probes by both physical association and also chemical reaction. “ Thus optical labels is broader than the fluorophores taught in the examples in the specification. The claims encompass anything which can be considered a probe. The specification teaches, “[0063] The term "probe" as used herein, refers to a molecule or a group of aggregated molecules that are coupled to a detectable label, or is suitable for coupling to a detectable label indirectly.” Thus while this encompasses nucleic acids, the specification clearly envisions probes are not limited to nucleic acids. The claims have been amended to limit the target molecule to nucleic acids or proteins.
Further claim 1 requires, “biological sample prepared for examination, comprising:a first target molecule bound, directly or indirectly, to a first plurality of probes each attached with a first optical label and a third optical label (a) the first and the second target molecules are nucleic acids or proteins,(b) the first the second optical labels have the same or overlapping color spectra but different intensities the-third- have the same or overlapping emission spectra but different intensities in third-and-fourth-target- wherein the first and the second third target molecules are optically distinguishable by comparing (i) a first intensity ratio of the first and the third optical labels associated with the first target molecule and (ii) a second intensity ratio of the second and the fourth optical labels associated with the second target molecule.”
Thus the independent claim is drawn to the labeling of a first target nucleic acid or protein with a first and third optical label and a second target nucleic acid or protein with a second and fourth optical labels. While the claims encompass anything this can be considered a probe and anything which can be considered an optical label the specification is limited to detection of nucleic and acids using known fluorescent dyes. The claims and specification do not provide adequate written description for any label in view of the breadth of label as set forth in the specification with the required functionality of the claim. Further the claims and specification do not provide adequate written description for any probe directly or indirectly labeled in view of the breadth of probe as set forth in the specification with the required functionality of the claim
Thus the claims lack adequate written description.
Response to Arguments
The response traverses the rejection in view of the amendment. As detailed in the rejection, the amendment does not address all issues.
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 1, 6, 16, 38- 41 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 1 has been amended to recite, “(b) the first and second optical labels have the same or overlapping color spectra but different intensity, (c) the third and fourth optical labels have the same or overlapping emission spectra but different intensities ” The recitation of same or overlapping color spectra but different intensity is a relative term.. The specification provides no specific guidance how to differentiate overlapping color spectra but different intensity from non-overlapping color spectra but different intensity. While the claim provides limitations with respect to intensity and spectra, the specification provides no limiting definitions of these terms, such as to be able to differentiate an overlapping from non-overlapping optical labels. Further the specification teaches the inventions is with respect to in situ hybridization. Thus distinguishable and indistinguishable are also dependent on magnification setting of microscope as something distinguishable on 100X or with one emission filter combination, is not distinguishable with 1X magnification and another emission filter combination. Further the claims provide no indication what is required of intensity.
While claim 16 recites, “wherein at least one target molecule is further bound to a quenching molecule or a signal enhancing molecule.” The specification recites, “a signal enhancing molecule” once on pgpub 0318. Thus it is unclear what is required or encompassed by this recitation.
Claim 41 contains the trademark/trade name Cy3 and Alexa 546. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe Cy3 and Alexa 546.and, accordingly, the identification/description is indefinite.
Claim 42 contains the trademark/trade name Cy5 and Cy5.5. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe Cy5 and Cy5.5 and, accordingly, the identification/description is indefinite.
Response to Arguments
The response traverses the rejection in view of the amendment. As detailed in the rejection, the amendment does not address all issues.
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.
Claim(s) 1, 3-6, 38, 42 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Zhang (Current Protocols in Human Genetics e70, Volume 99 Published in Wiley Online Library (wileyonlinelibrary.com). doi: 10.1002/cphg.70C (c) 2018 John Wiley & Sons, Inc..)
The claims are to a product a biological sample. Claims encompass any first, second third and fourth target molecule. The claims require each target molecule is bound to at least a first label or a first label in combination with other labels. While the claim requires a first color channel is different from a second color channel the claims and specification do not define how they are different. Thus the claims are very broad.
With regards to claim 1, Zhang teaches a multicolor FISH for analysis of a genome (title). Zhang teaches
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Thus Zhang teachings of chromosome 5 labeled with cy3 and TR. While chromosome 7 is labeled with cy5 and cy5.5
Zhang teaches is figures 3 and figure 4 the labeling patterns encompassed by the claims.(page 3)
With regards to claims 6, Zhang teaches
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With regards to claim 38, Zhang teaches cy5 and cyc5.5 are peak emissions of less than 100 nm.
With regards to claim 42, Zhang teaches cy5 and cyc5.5.
Response to Arguments
The response traverses the rejection in view of the amendment. This argument has been thoroughly reviewed but is not considered persuasive in view of the rejection as amended in view of the claim amendments.
Claim Rejections - 35 USC § 103
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 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.
Claim(s) 1, 3-6, 16, 38, 42 is/are rejected under 35 U.S.C. 103 as being unpatentable over Zhang (Current Protocols in Human Genetics e70, Volume 99 Published in Wiley Online Library (wileyonlinelibrary.com). doi: 10.1002/cphg.70C (c) 2018 John Wiley & Sons, Inc..) and Bayani (Current Protocols in Cell Biology (2004) 22.4.1-22.4.52)
The claims are to a product a biological sample. Claims encompass any first, second third and fourth target molecule. The claims require each target molecule is bound to at least a first label or a first label in combination with other labels. While the claim requires a first color channel is different from a second color channel the claims and specification do not define how they are different. Thus the claims are very broad.
With regards to claim 1, Zhang teaches a multicolor FISH for analysis of a genome (title). Zhang teaches
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Thus Zhang teachings of chromosome 5 labeled with cy3 and TR. While chromosome 7 is labeled with cy5 and cy5.5
Zhang teaches is figures 3 and figure 4 the labeling patterns encompassed by the claims.(page 3)
With regards to claims 6, Zhang teaches
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With regards to claim 38, Zhang teaches cy5 and cyc5.5 are peak emissions of less than 100 nm.
With regards to claim 42, Zhang teaches cy5 and cyc5.5.
Zhang does not specifically teach the use of an enhancing agent or quencher.
However, Bayani teaches, “The signals are protected from rapid quenching through the reagents used in the mounting medium. These counterstains in mounting (antifade) medium can be purchased commercially. If the counterstain is prepared in the laboratory, be sure to use high quality glycerol, since some lower quality glycerols can cause autofluorescence. The concentration of counterstain may require adjustment. Higher counterstain concentrations may obscure FISH signals. If this is the case, dilute the counterstain in antifade by adding more glycerol and PBS in amounts that will be consistent with the final concentrations.” (page 22.4.47)
Thus it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claims to use an antifade (enhancing reagent ) on the prepared sample of Zhang. The artisan would have a reasonable expectation of success as the artisan is merely using known reagents on known samples.
Response to Arguments
The response traverses the rejection in view of the amendment. This argument has been thoroughly reviewed but is not considered persuasive in view of the rejection as amended in view of the claim amendments.
Claim(s) 1, 3-6, , 38,41- 42 is/are rejected under 35 U.S.C. 103 as being unpatentable over Zhang (Current Protocols in Human Genetics e70, Volume 99 Published in Wiley Online Library (wileyonlinelibrary.com). doi: 10.1002/cphg.70C (c) 2018 John Wiley & Sons, Inc..) and Kim (US2018/0044736)
The claims are to a product a biological sample. Claims encompass any first, second third and fourth target molecule. The claims require each target molecule is bound to at least a first label or a first label in combination with other labels. While the claim requires a first color channel is different from a second color channel the claims and specification do not define how they are different. Thus the claims are very broad.
With regards to claim 1, Zhang teaches a multicolor FISH for analysis of a genome (title). Zhang teaches
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565
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Thus Zhang teachings of chromosome 5 labeled with cy3 and TR. While chromosome 7 is labeled with cy5 and cy5.5
Zhang teaches is figures 3 and figure 4 the labeling patterns encompassed by the claims.(page 3)
With regards to claims 6, Zhang teaches
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With regards to claim 38, Zhang teaches cy5 and cyc5.5 are peak emissions of less than 100 nm.
With regards to claim 42, Zhang teaches cy5 and cyc5.5.
Zhang does not specifically teach the use of an cy3 and Alexa 546.
However, Kim teaches methods of detection including FISH (0163). Kim further teaches Cy3 and Alexa 546 can be used as fluorescent labels (0180).
Thus it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claims to use an use cy3 and Alexa 546 as labels for a nucleic acid prepared sample of Zhang. The artisan would be motivated as Kim suggests as cy3 and Alexa 546 for fluorescent labeling of nucleic acids. The artisan would have a reasonable expectation of success as the artisan is merely using known reagents on known samples.
Response to Arguments
This is a new ground of rejection necessitated by amendment.
Claim(s) 1, 3-6, , 38,41- 42 is/are rejected under 35 U.S.C. 103 as being unpatentable over Zhang (Current Protocols in Human Genetics e70, Volume 99 Published in Wiley Online Library (wileyonlinelibrary.com). doi: 10.1002/cphg.70C (c) 2018 John Wiley & Sons, Inc..) and Player ((J Histochem Cytochem 49:603–611, 2001)
The claims are to a product a biological sample. Claims encompass any first, second third and fourth target molecule. The claims require each target molecule is bound to at least a first label or a first label in combination with other labels. While the claim requires a first color channel is different from a second color channel the claims and specification do not define how they are different. Thus the claims are very broad.
With regards to claim 1, Zhang teaches a multicolor FISH for analysis of a genome (title). Zhang teaches
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259
565
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Thus Zhang teachings of chromosome 5 labeled with cy3 and TR. While chromosome 7 is labeled with cy5 and cy5.5
Zhang teaches is figures 3 and figure 4 the labeling patterns encompassed by the claims.(page 3)
With regards to claims 6, Zhang teaches
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With regards to claim 38, Zhang teaches cy5 and cyc5.5 are peak emissions of less than 100 nm.
With regards to claim 42, Zhang teaches cy5 and cyc5.5.
Player does not specifically teach the use branched DNA.
However, Player teaches, “Branched DNA (bDNA) signal amplification technology has been used extensively in a microwell format to detect and quantify specific nucleic acid sequences. Inherently quantitative and highly reproducible, bDNA technology utilizes nonradioactive synthetic oligonucleotide probes and can readily be applied to the detection of any nucleic acid target for which a sequence is known” (page 603, 1st column, 2nd column).Player teaches, “The bDNA ISH method described here provides a rapid, sensitive, and reproducible means for detection of specific DNA and mRNA sequences in various cell types (page 607, 22ncd column, bottom) Player teaches, “In summary, we have developed a bDNA ISH method for sensitive detection of DNA target sequences that overcomes many of the challenges facing ISH techniques today. Based on bDNA signal amplification technology, the bDNA ISH method is highly sensitive (can detect one or two copies of DNA target per cell), specific, and provides subcellular localization of the target sequence. By modifying a few steps in the bDNA ISH procedure, detection of mRNA or DNA targets can be achieved using the same set of DNA oligonucleotide probes. The bDNA ISH method is nonisotopic, rapid (yields results within a day), can be adapted to generate chromogenic and/or fluorescent signals, and should be amenable to automation and quantification. Given its ease of use and reliability, the bDNA ISH method is an attractive alternative for sensitive detection of nucleic acid sequences in a well-preserved morphological context.” (page 601, bottom 1st column-2nd column).
Thus it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claims to use an use branch DNA as labels for a nucleic acid prepared sample of Zhang. The artisan would be motivated as Player teaches branched DNA is sensitive and can detect low abundance nucleic acids. The artisan would have a reasonable expectation of success as the artisan is merely using known reagents on known samples.
Response to Arguments
This is a new ground of rejection necessitated by amendment.
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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/Steven Pohnert/ Primary Examiner, Art Unit 1683