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 7/17/2026.
Claims 1, 5-7, 9, 11-12, 14-15, 20 have been amended.
Claims 1, 5-7, 9-12, 14-15, 19-20 are being examined.
In view of the certified translation of the foreign priority document, the claims are being give priority to the Chinese priority document.
The art rejection has been withdrawn in view of the amendment to the independent claim.
Priority
The instant application was filed 02/03/2024 and is a continuation of PCT/CN2022/110533 filed 08/05/2022 and claims foreign priority to CN202110899807.3, filed 08/06/2021.
Specification
The specification is objected to as failing to provide proper antecedent basis for the claimed subject matter. See 37 CFR 1.75(d)(1) and MPEP § 608.01(o). Correction of the following is required:
Claim 1 has been amended to recite, “image information,” “step e, “ “step f,” “step g,” “step h,” “step I,” “step j,” “step k,” “step l,” “step m,” “step n,” “step o,” “image information, “ “capturing mRNA,” “washing the surface,” “ step o. associating the sequence information with spatial points of the tissue sample based on the first location domain. the second location domain and the tissue image information, thereby obtaining the spatial omic information of the tissue sample.”
Response to Arguments
This is a new ground of objection necessitated by amendment.
Claim Objections
Claims 1, 5-7, 9-12, 14-15, 19-20 objected to because of the following informalities:
The instant amended claims have presented claims which are not completely legible and appear pixelated. For example it is hard to discern a period from a comma
Appropriate correction is required.
Response to Arguments
This is a new ground of objection necessitated by amendment.
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, 5-7, 9-12, 14-15, 19-20 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.
MPEP 2163 IB New or amended claims section II
With respect to newly added or amended claims, applicant should show support in the original disclosure for the new or amended claims. See, e.g., Hyatt v. Dudas, 492 F.3d 1365, 1370, n.4 (Fed. Cir. 2007) (citing MPEP § 2163.04 which provides that a "simple statement such as ‘applicant has not pointed out where the new (or amended) claim is supported, nor does there appear to be a written description of the claim limitation ‘___’ in the application as filed’ may be sufficient where the claim is a new or amended claim, the support for the limitation is not apparent, and applicant has not pointed out where the limitation is supported."); see also MPEP §§ 714.02 and 2163.06 ("Applicant should ... specifically point out the support for any amendments made to the disclosure."); and MPEP § 2163.04
Independent claim 1 has been amended to recite:
A method for high-resolution spatial omic detection of a tissue
sample, comprising:
step a, providing a device comprising a slide with a microwell array, and dispersing microcarriers in the microwell array, with each microwell and a microcarrier in each microwell forming a microwell reaction chamber; and further comprising:
step b, aligning microchannels arranged in parallel are aligned with a microwell reaction chamber array in a first direction; introducing different first molecular identifiers into the microchannels, respectively; ligating the first molecular identifiers are ligated to the microcarriers; wherein the first molecular identifier is first nucleic acid molecular identifier, comprises a nucleic acid sequence in direction from 5' to 3’: (i) a universal domain; (ii) first location domains, wherein the first location domains are different from one another, and information of a sequence of the first location domain corresponds to a liquid position where the sequence of the first location domain is introduced into the microchannel; and
(iii) a ligation domain, the sequence being used for ligating first and second nucleic acid molecular identifiers; step C, aligning microchannels arranged in parallel with the microwell reaction chamber array in a second direction perpendicular to the first direction of the microchannel;
introducing different second molecular identifiers are introduced into the microchannels, respectively; conjugating the first molecular identifier is conjugated with the second molecular identifier; wherein the second molecular identifier is sequence, namely a second nucleic acid molecular identifier- preferably comprising at nucleic acid sequence in direction from 5' to 3’
a) a ligation domain complementary region, wherein the ligation domain complementary region is hybridized with the ligation domain by Watson-Crick base pairing;
b) second location domains, wherein the second location domains are different from one another from one another, and information of sequence of the second location domain corresponds to a liquid position where the sequence of the second location domain is introduced into the microchannel; and
c) a molecular marker, used for providing information of a nucleic acid class for
hybridization with a nucleic acid molecular identifier and distinguishing between nucleic acid types for hybridization with different nucleic acid molecular identifiers, wherein the second nucleic acid molecular identifiers conjugated with a same microcarrier preferably comprise different molecular markers; and
d) a capture domain precursor, comprising a nucleic acid sequence for forming a capture domain;
wherein "different" in the different first/second nucleic acid molecular identifiers refers to that the first location domains of the first molecular identifiers introduced into each of the microchannels arranged in parallel is different from one another; the second location domains of the second molecular identifiers introduced into each of the microchannels arranged in parallel is different from one another, and a combination of one first location domain and one second location domain uniquely identifies the microwell reaction chamber, and the microwell reaction chamber is associated with a spatial position of the tissue sample based on the tissue image information and
step d, co-incubating hybridized and complemented first and second molecular identifiers and a reaction mixture liquid, and ligating the microcarrier to unique
molecular identifier; wherein the unique molecular identifier is a unique nucleic acid molecular identifier, preferably
comprising a nucleic acid sequence from 5' to 3':
1) a universal domain;
2) a first location domain;
3) a ligation domain;
4) a second location domain;
5) a molecular marker; and
6) a capture domain, comprising to a poly-T oligonucleotide sequence;
wherein the unique nucleic acid molecular identifier comprises a nucleic acid sequence formed after the complementation of the first nucleic acid molecular identifier and the second nucleic acid molecular identifier or a nucleic acid sequence obtained by extending, amplifying, or ligating the complemented nucleic acid sequence; and the unique nucleic acid molecular identifier refers to a nucleic acid sequence that is different from other nucleic acid molecular identifiers ligated to the microcarriers and related to cells or tissues;
step e. adding solid phase or liquid-phase compound to the microwell reaction chamber array in which the microcarriers are stored:
step f attaching a tissue sample to a surface of the microwell array, thereby embedding or spreading the tissue sample in or on the microwells;
step g, imaging the tissue samples on the microwell array to obtain tissue image
information corresponding to the microwell array:
step h. covering a surface of the microwells with a porous membrane:
step i. adding a tissue permeabilizing liquid to the surface of the porous membrane to release an mRNA from the tissue sample in the microwell:
step j. capturing the released mRNA by the capture domain of the unique nucleic acid molecular identifier:
step k. washing the surface of the porous membrane;
step l. incubating a reverse transcription reaction mixture liquid in the microwell array to extend the unique nucleic acid molecular identifier using the captured mRNA. thereby obtaining a cDNA:
step m. amplifying and creating a library for cDNA:
step n analyzing the library to obtain sequence information of the captured RNA, the molecular marker. the first location domain, and the second location domain: and step 0. associating the sequence information with spatial points of the tissue sample based on the first location domain. the second location domain and the tissue image information, thereby obtaining the spatial omic information of the tissue sample.”
The response provides no specific indication of where support for the instant claims can be found. Review and searching of the specification did not reveal antecedent basis for “step e, “ “step f,” “step g,” “step h,” “step I,” “step j,” “step k,” “step l,” “step m,” “step n,” “step o,” “image information, “ “capturing mRNA,” “washing the surface,” “ step o. associating the sequence information with spatial points of the tissue sample based on the first location domain. the second location domain and the tissue image information, thereby obtaining the spatial omic information of the tissue sample.”
Further claim 9 has been amended to recite, “10 or more.” Review and searching of the specification did not reveal support for the amendment.
Response to Arguments
This is a new ground of rejection necessitated by amendment.
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, 5-7, 9-12, 14-15, 19-20 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 is indefinite because it lacks a positive active step relating back to the preamble. The preamble recites a method of high-resolution spatial-omic detection of a tissue sample, however the last positive active step is drawn to associating the sequence information with spatial points of the tissue sample based on the first location domain. the second location domain and the tissue image information. Therefore it is unclear as to whether the method is drawn to high-resolution spatial-omic detection of a tissue sample or associating the sequence information with spatial points of the tissue sample based on the first location domain. the second location domain and the tissue image information.
Claim 1 has been amended to recite, “first location domains, wherein the first location domains are different from one another, and information of a sequence of the first location domain corresponds to a liquid position where the sequence of the first location domain is introduced into the microchannel.” The metes and bounds are vague, unclear and incomplete hot a first location domain “corresponds” to a liquid position.
Claim 1 recites, “a) a ligation domain complementary region, wherein the ligation domain complementary region is hybridized with the ligation domain by Watson-Crick base pairing.” The claim is confusing and unclear as the claim appears to be defining the ligation domain as complementary to the ligation domain, which is a circular definition.
Claim 1 has been amended to recite, “second location domains, wherein the second location domains are different from one another from one another, and information of sequence of the second location domain corresponds to a liquid position where the sequence of the second location domain is introduced into the microchannel.” The metes and bounds are vague, unclear and incomplete hot a first location domain “corresponds” to a liquid position.
Claim 1 recites, “wherein "different" in the different first/second nucleic acid molecular identifiers refers to that the first location domains of the first molecular identifiers introduced into each of the microchannels arranged in parallel is different from one another; the second location domains of the second molecular identifiers introduced into each of the microchannels arranged in parallel is different from one another, and a combination of one first location domain and one second location domain uniquely identifies the microwell reaction chamber, and the microwell reaction chamber is associated with a spatial position of the tissue sample based on the tissue image information.” The metes and bounds are unclear what is required of different in molecular identifiers which are not ligated. Further the recitation of “the tissue image information” lacks antecedent basis. Thus the claim is vague and unclear.
Claim 1 has been amended to recite , “imaging the tissue samples on the microwell array to obtain tissue image information corresponding to the microwell array.” The recitation is confusing, unclear and incomplete how . tissue image information corresponding to the microwell array.
Claim 1 has been amended to recite, “associating the sequence information with spatial points of the tissue sample based on the first location domain. the second location domain and the tissue image information, thereby obtaining the spatial omic information of the tissue sample.” This is vague, unclear and incomplete how associating is done.
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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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
