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
This Non-Final Office Action is responsive to the communication received 11/13/2025.
Election/Restrictions
Applicant’s election without traverse in the Reply filed on 11/13/2025 of Group I, claims 1-4 is acknowledged.
Applicant has elected in the Reply filed on 11/13/2025 the following species:
A. the method wherein both the removing of b) the removing of d) comprise contacting the sample with an exonuclease (claim 3)
Because applicant did not distinctly and specifically point out the supposed errors in the species election requirement, the election has been treated as an election without traverse (MPEP § 818.03(a)).
The Restriction/Election Requirements are thus deemed proper and are made FINAL.
Claims 1-4 are pending.
Claims 5-12 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the Reply filed on 11/13/2025.
Claims 1-4 are under examination in this Office Action.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-4 are rejected under 35 U.S.C. 101 because the claimed invention is directed to nonstatutory subject matter. The claim(s) does/do not fall within at least one of the four categories of patent eligible subject matter because the claimed invention is directed to a judicial exception, an abstract idea, without significantly more. Claims 2-4 depend directly or indirectly from claim 1.
The claim 1 limitations directed to the abstract idea are h) determining nucleotide sequences of the plurality of structurally different target polynucleotides comprising the immune specific gene sequences from the products.
The claim 2 limitations directed to the abstract idea are i) comparing the quantity or identity of sequences of the plurality of structurally different target polynucleotides comprising the immune gene sequences targeting the HPA-1a antigen from at least one sample to sequences of polynucleotides comprising the immune gene sequences targeting the HPA-1a antigen from a control or from a second sample obtained at an earlier time point in the woman's pregnancy.
The above claim 1 and claim 2 limitations are directed toward mental processes of determining and comparing.
The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claim recites additional elements that consist of well understood, routine, conventional activity already engaged in by the scientific community.
The claim 1 limitations directed to well understood, routine, conventional activity already engaged in by the scientific community are a method comprising: a) providing a reaction mixture comprising: i) a plurality of structurally different target polynucleotides from the pregnant woman, wherein individual target polynucleotides of the plurality comprise immune cell receptor V, J, and optionally C or D gene regions; and ii) a plurality of immune cell receptor V gene specific primers, wherein the immune cell receptor V gene specific primers comprise at least 10 structurally distinct primers having the following regions from 5′ to 3′: [5′-Phos], [SPLINT], [BARCODE], and [FW], wherein: [5′-Phos] comprises a 5′ phosphate; [SPLINT] comprises an adaptor hybridization site of 2-8 nucleotides in length; [BARCODE] comprises a barcode region of at least 6 nucleotides in length, wherein each nucleotide of the barcode region is independently selected from the group consisting of N and W; and [FW] of each immune cell receptor V gene specific primer comprises a structurally distinct region that specifically hybridizes to a framework 1, framework 2, or framework 3 region of an immune cell receptor V gene, wherein the immune cell receptor V gene specific primers are hybridized to the V gene regions of the target polynucleotides; b) extending the hybridized immune cell receptor V gene specific primers with a polymerase, and then removing un-extended immune cell receptor V gene specific primers, if present, wherein the extended immune cell receptor V gene specific primers comprise at least a portion of the immune cell receptor V region, optionally the immune cell receptor D region, at least a portion of the immune cell receptor C region, and at least a portion of the immune cell receptor J region; c) hybridizing a first universal adaptor to the [SPLINT] adaptor hybridization site of the extended immune cell receptor V gene specific primers, wherein said universal adaptor is a double-stranded adaptor, comprising: a 5′ single-stranded overhang region which can be hybridized to the SPLINT adaptor hybridization site of said extended primers; d) ligating the hybridized first universal adapters to the extended immune cell receptor V gene specific primers, and then removing un-ligated adapters, if present; e) hybridizing a plurality of immune cell receptor J gene specific primers to the J region portions of the extended immune cell receptor V gene specific primers, wherein the immune cell receptor J gene specific primers comprise a 3′ J gene hybridizing region and a 5′ second universal adapter region or hybridizing a plurality of immune cell receptor C gene specific primers to the C region portions of the extended immune cell receptor V gene specific primers, wherein the immune cell receptor C gene specific primers comprise a 3′ C gene hybridizing region and a 5′ second universal adapter region; and f) extending the hybridized immune cell receptor J gene specific primers or C gene specific primers with a polymerase, thereby forming a plurality of structurally different double-stranded products, each comprising at least a portion of the immune cell receptor V region, optionally the immune cell receptor D region, and at least a portion of the immune cell receptor J region or C region flanked by a first and second universal adapter sequence; g) amplifying the plurality of structurally different double-stranded products with thereby enriching the plurality of structurally different target polynucleotides comprising immune gene sequences.
Berka et al. (06/10/2021) US Patent Application Publication 2021/0172015 A1 (hereinafter known as "Berka") teaches a method comprising: a) providing a reaction mixture comprising: i) a plurality of structurally different target polynucleotides from the pregnant woman, wherein individual target polynucleotides of the plurality comprise immune cell receptor V, J, and optionally C or D gene regions; and ii) a plurality of immune cell receptor V gene specific primers, wherein the immune cell receptor V gene specific primers comprise at least 10 structurally distinct primers having the following regions from 5′ to 3′: [5′-Phos], [SPLINT], [BARCODE], and [FW], wherein: [5′-Phos] comprises a 5′ phosphate; [SPLINT] comprises an adaptor hybridization site of 2-8 nucleotides in length; [BARCODE] comprises a barcode region of at least 6 nucleotides in length, wherein each nucleotide of the barcode region is independently selected from the group consisting of N and W; and [FW] of each immune cell receptor V gene specific primer comprises a structurally distinct region that specifically hybridizes to a framework 1, framework 2, or framework 3 region of an immune cell receptor V gene, wherein the immune cell receptor V gene specific primers are hybridized to the V gene regions of the target polynucleotides; b) extending the hybridized immune cell receptor V gene specific primers with a polymerase, and then removing un-extended immune cell receptor V gene specific primers, if present, wherein the extended immune cell receptor V gene specific primers comprise at least a portion of the immune cell receptor V region, optionally the immune cell receptor D region, at least a portion of the immune cell receptor C region, and at least a portion of the immune cell receptor J region; c) hybridizing a first universal adaptor to the [SPLINT] adaptor hybridization site of the extended immune cell receptor V gene specific primers, wherein said universal adaptor is a double-stranded adaptor, comprising: a 5′ single-stranded overhang region which can be hybridized to the SPLINT adaptor hybridization site of said extended primers; d) ligating the hybridized first universal adapters to the extended immune cell receptor V gene specific primers, and then removing un-ligated adapters, if present; e) hybridizing a plurality of immune cell receptor J gene specific primers to the J region portions of the extended immune cell receptor V gene specific primers, wherein the immune cell receptor J gene specific primers comprise a 3′ J gene hybridizing region and a 5′ second universal adapter region or hybridizing a plurality of immune cell receptor C gene specific primers to the C region portions of the extended immune cell receptor V gene specific primers, wherein the immune cell receptor C gene specific primers comprise a 3′ C gene hybridizing region and a 5′ second universal adapter region; and f) extending the hybridized immune cell receptor J gene specific primers or C gene specific primers with a polymerase, thereby forming a plurality of structurally different double-stranded products, each comprising at least a portion of the immune cell receptor V region, optionally the immune cell receptor D region, and at least a portion of the immune cell receptor J region or C region flanked by a first and second universal adapter sequence; g) amplifying the plurality of structurally different double-stranded products with thereby enriching the plurality of structurally different target polynucleotides comprising immune gene sequences (see Figure 1 and [0055] to [0137]).
Claim Rejections - 35 USC § 103(a)
The following is a quotation of 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. § 103(a) are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
5. Secondary considerations (objective evidence of nonobviousness): a) commercial success; b) long felt need; c) evidence of unexpected results; d) skepticism of experts; and e) copying.
Common Ownership of Claimed Invention Presumed
This application currently names joint inventors. In considering patentability of the claims under 35 U.S.C. 103(a), the Examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the Examiner to consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103(a).
Claims 1-4 are rejected under 35 U.S.C. 103(a) as being unpatentable over Berka et al. (06/10/2021) US Patent Application Publication 2021/0172015 A1 (hereinafter known as "Berka") in view of Sachs (2020) Transfusion and Apheresis Science volume 59 document 102709 pages 1 to 6 cited in the 11/13/2025 IDS (hereinafter known as "Sachs").
With regards to claims 1-3, Berka teaches:
a) as in claims 1-3, a method of quantifying immune specific genes in a patient encoding an antigen, the method comprising, a) providing a reaction mixture comprising: i) a plurality of structurally different target polynucleotides from the pregnant woman, wherein individual target polynucleotides of the plurality comprise immune cell receptor V, J, and optionally C or D gene regions; and ii) a plurality of immune cell receptor V gene specific primers, wherein the immune cell receptor V gene specific primers comprise at least 10 structurally distinct primers having the following regions from 5′ to 3′: [5′-Phos], [SPLINT], [BARCODE], and [FW], wherein: [5′-Phos] comprises a 5′ phosphate; [SPLINT] comprises an adaptor hybridization site of 2-8 nucleotides in length; [BARCODE] comprises a barcode region of at least 6 nucleotides in length, wherein each nucleotide of the barcode region is independently selected from the group consisting of N and W; and [FW] of each immune cell receptor V gene specific primer comprises a structurally distinct region that specifically hybridizes to a framework 1, framework 2, or framework 3 region of an immune cell receptor V gene, wherein the immune cell receptor V gene specific primers are hybridized to the V gene regions of the target polynucleotides; b) extending the hybridized immune cell receptor V gene specific primers with a polymerase, and then removing un-extended immune cell receptor V gene specific primers, if present, wherein the extended immune cell receptor V gene specific primers comprise at least a portion of the immune cell receptor V region, optionally the immune cell receptor D region, at least a portion of the immune cell receptor C region, and at least a portion of the immune cell receptor J region; c) hybridizing a first universal adaptor to the [SPLINT] adaptor hybridization site of the extended immune cell receptor V gene specific primers, wherein said universal adaptor is a double-stranded adaptor, comprising: a 5′ single-stranded overhang region which can be hybridized to the SPLINT adaptor hybridization site of said extended primers; d) ligating the hybridized first universal adapters to the extended immune cell receptor V gene specific primers, and then removing un-ligated adapters, if present; e) hybridizing a plurality of immune cell receptor J gene specific primers to the J region portions of the extended immune cell receptor V gene specific primers, wherein the immune cell receptor J gene specific primers comprise a 3′ J gene hybridizing region and a 5′ second universal adapter region or hybridizing a plurality of immune cell receptor C gene specific primers to the C region portions of the extended immune cell receptor V gene specific primers, wherein the immune cell receptor C gene specific primers comprise a 3′ C gene hybridizing region and a 5′ second universal adapter region; and f) extending the hybridized immune cell receptor J gene specific primers or C gene specific primers with a polymerase, thereby forming a plurality of structurally different double-stranded products, each comprising at least a portion of the immune cell receptor V region, optionally the immune cell receptor D region, and at least a portion of the immune cell receptor J region or C region flanked by a first and second universal adapter sequence; g) amplifying the plurality of structurally different double-stranded products with thereby enriching the plurality of structurally different target polynucleotides comprising immune gene sequences; and h) determining nucleotide sequences of the plurality of structurally different target polynucleotides comprising the immune specific gene sequences from the products; further comprising i) comparing the quantity or identity of sequences of the plurality of structurally different target polynucleotides comprising the immune gene sequences targeting the antigen from at least one sample to sequences of polynucleotides comprising the immune gene sequences targeting the antigen from a control or from a second sample obtained at an earlier time point in the patient; wherein the removing of b) and the removing of d) both comprise contacting the sample with an exonuclease (see Figure 1 and [0055] to [0137]).
Berka does not explicitly teach:
a) as in claims 1-2 and 4, a pregnant woman carrying a fetus encoding an HPA-1a antigen, wherein the pregnant woman lacks the HPA-1a antigen; administering one or more agent or treatment to the woman or fetus to reduce the effect of FNAIT on the fetus.
With regards to claims 1-2 and 4, Sachs teaches:
a) as in claims 1-2 and 4, a pregnant woman carrying a fetus encoding an HPA-1a antigen, wherein the pregnant woman lacks the HPA-1a antigen; administering one or more agent or treatment to the woman or fetus to reduce the effect of FNAIT on the fetus (see entire document especially abstract, Figure 1 and pages 1 to 4).
One of ordinary skill in the art before the time of the effective filing date of the claimed invention would have had a reasonable expectation of success in arriving at the Applicant's invention as claimed with the above cited references before them. One of ordinary skill in the art before the time of the effective filing date of the claimed invention would have recognized the advantages of substituting Sachs's HPA-1a for Berka's immune receptor to identify patients who could benefit from treatment to reduce the effect of FNAIT. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art before the time of the effective filing date of the claimed invention.
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 1-4 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-11 of U.S. Patent Number 11098360.
Although the conflicting claims are not identical, they are not patentably distinct from each other because the present claim 1 is drawn to a method of quantifying immune specific genes in a pregnant woman carrying a fetus encoding an HPA-1a antigen, wherein the pregnant woman lacks the HPA-1a antigen, the method comprising, a) providing a reaction mixture comprising: i) a plurality of structurally different target polynucleotides from the pregnant woman, wherein individual target polynucleotides of the plurality comprise immune cell receptor V, J, and optionally C or D gene regions; and ii) a plurality of immune cell receptor V gene specific primers, wherein the immune cell receptor V gene specific primers comprise at least 10 structurally distinct primers having the following regions from 5′ to 3′: [5′-Phos], [SPLINT], [BARCODE], and [FW], wherein: [5′-Phos] comprises a 5′ phosphate; [SPLINT] comprises an adaptor hybridization site of 2-8 nucleotides in length; [BARCODE] comprises a barcode region of at least 6 nucleotides in length, wherein each nucleotide of the barcode region is independently selected from the group consisting of N and W; and [FW] of each immune cell receptor V gene specific primer comprises a structurally distinct region that specifically hybridizes to a framework 1, framework 2, or framework 3 region of an immune cell receptor V gene, wherein the immune cell receptor V gene specific primers are hybridized to the V gene regions of the target polynucleotides; b) extending the hybridized immune cell receptor V gene specific primers with a polymerase, and then removing un-extended immune cell receptor V gene specific primers, if present, wherein the extended immune cell receptor V gene specific primers comprise at least a portion of the immune cell receptor V region, optionally the immune cell receptor D region, at least a portion of the immune cell receptor C region, and at least a portion of the immune cell receptor J region; c) hybridizing a first universal adaptor to the [SPLINT] adaptor hybridization site of the extended immune cell receptor V gene specific primers, wherein said universal adaptor is a double-stranded adaptor, comprising: a 5′ single-stranded overhang region which can be hybridized to the SPLINT adaptor hybridization site of said extended primers; d) ligating the hybridized first universal adapters to the extended immune cell receptor V gene specific primers, and then removing un-ligated adapters, if present; e) hybridizing a plurality of immune cell receptor J gene specific primers to the J region portions of the extended immune cell receptor V gene specific primers, wherein the immune cell receptor J gene specific primers comprise a 3′ J gene hybridizing region and a 5′ second universal adapter region or hybridizing a plurality of immune cell receptor C gene specific primers to the C region portions of the extended immune cell receptor V gene specific primers, wherein the immune cell receptor C gene specific primers comprise a 3′ C gene hybridizing region and a 5′ second universal adapter region; and f) extending the hybridized immune cell receptor J gene specific primers or C gene specific primers with a polymerase, thereby forming a plurality of structurally different double-stranded products, each comprising at least a portion of the immune cell receptor V region, optionally the immune cell receptor D region, and at least a portion of the immune cell receptor J region or C region flanked by a first and second universal adapter sequence; g) amplifying the plurality of structurally different double-stranded products with thereby enriching the plurality of structurally different target polynucleotides comprising immune gene sequences; and h) determining nucleotide sequences of the plurality of structurally different target polynucleotides comprising the immune specific gene sequences from the products and claim 1 in U.S. Patent Number 11098360 is drawn to a method for enriching from a sample a plurality of structurally different target polynucleotides, the method comprising: a) providing a reaction mixture comprising: i) a plurality of structurally different target polynucleotides, wherein individual target polynucleotides of the plurality comprise immune cell receptor V, J, and optionally C or D gene regions; and ii) a plurality of immune cell receptor V gene specific primers, wherein the immune cell receptor V gene specific primers comprise at least 10 structurally distinct primers having the following regions from 5′ to 3′: [5′-Phos], [SPLINT], [BARCODE], and [FW], wherein: [5′-Phos] comprises a 5′ phosphate; [SPLINT] comprises an adaptor hybridization site of 2-8 nucleotides in length; [BARCODE] comprises a barcode region of at least 6 nucleotides in length, wherein each nucleotide of the barcode region is independently selected from the group consisting of N and W; and [FW] of each immune cell receptor V gene specific primer comprises a structurally distinct region that specifically hybridizes to a framework 1, framework 2, or framework 3 region of an immune cell receptor V gene, wherein the immune cell receptor V gene specific primers are hybridized to the V gene regions of the target polynucleotides; b) extending the hybridized immune cell receptor V gene specific primers with a polymerase, and then removing un-extended immune cell receptor V gene specific primers, if present, wherein the extended immune cell receptor V gene specific primers comprise at least a portion of the immune cell receptor V region, optionally the immune cell receptor D region, at least a portion of the immune cell receptor C region, and at least a portion of the immune cell receptor J region; c) hybridizing a first universal adaptor to the [SPLINT] adaptor hybridization site of the extended immune cell receptor V gene specific primers; wherein said universal adaptor is a double-stranded adaptor, comprising: a 5′ single-stranded overhang region which can be hybridized to the SPLINT adaptor hybridization site of said extended primers; d) ligating the hybridized first universal adapters to the extended immune cell receptor V gene specific primers, and then removing un-ligated adapters, if present; e) hybridizing a plurality of immune cell receptor J gene specific primers to the J region portions of the extended immune cell receptor V gene specific primers, wherein the immune cell receptor J gene specific primers comprise a 3′ J gene hybridizing region and a 5′ second universal adapter region or hybridizing a plurality of immune cell receptor C gene specific primers to the C region portions of the extended immune cell receptor V gene specific primers, wherein the immune cell receptor C gene specific primers comprise a 3′ C gene hybridizing region and a 5′ second universal adapter region; and f) extending the hybridized immune cell receptor J gene specific primers or C gene specific primers with a polymerase, thereby forming a plurality of structurally different double-stranded products, each comprising at least a portion of the immune cell receptor V region, optionally the immune cell receptor D region, and at least a portion of the immune cell receptor J region or C region flanked by a first and second universal adapter sequence.
Therefore, the present claims are obvious in view of the claims of U.S. Patent Number 11098360.
Claims 1-4 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-11 of U.S. Patent Number 11306356.
Although the conflicting claims are not identical, they are not patentably distinct from each other because the present claim 1 is drawn to a method of quantifying immune specific genes in a pregnant woman carrying a fetus encoding an HPA-1a antigen, wherein the pregnant woman lacks the HPA-1a antigen, the method comprising, a) providing a reaction mixture comprising: i) a plurality of structurally different target polynucleotides from the pregnant woman, wherein individual target polynucleotides of the plurality comprise immune cell receptor V, J, and optionally C or D gene regions; and ii) a plurality of immune cell receptor V gene specific primers, wherein the immune cell receptor V gene specific primers comprise at least 10 structurally distinct primers having the following regions from 5′ to 3′: [5′-Phos], [SPLINT], [BARCODE], and [FW], wherein: [5′-Phos] comprises a 5′ phosphate; [SPLINT] comprises an adaptor hybridization site of 2-8 nucleotides in length; [BARCODE] comprises a barcode region of at least 6 nucleotides in length, wherein each nucleotide of the barcode region is independently selected from the group consisting of N and W; and [FW] of each immune cell receptor V gene specific primer comprises a structurally distinct region that specifically hybridizes to a framework 1, framework 2, or framework 3 region of an immune cell receptor V gene, wherein the immune cell receptor V gene specific primers are hybridized to the V gene regions of the target polynucleotides; b) extending the hybridized immune cell receptor V gene specific primers with a polymerase, and then removing un-extended immune cell receptor V gene specific primers, if present, wherein the extended immune cell receptor V gene specific primers comprise at least a portion of the immune cell receptor V region, optionally the immune cell receptor D region, at least a portion of the immune cell receptor C region, and at least a portion of the immune cell receptor J region; c) hybridizing a first universal adaptor to the [SPLINT] adaptor hybridization site of the extended immune cell receptor V gene specific primers, wherein said universal adaptor is a double-stranded adaptor, comprising: a 5′ single-stranded overhang region which can be hybridized to the SPLINT adaptor hybridization site of said extended primers; d) ligating the hybridized first universal adapters to the extended immune cell receptor V gene specific primers, and then removing un-ligated adapters, if present; e) hybridizing a plurality of immune cell receptor J gene specific primers to the J region portions of the extended immune cell receptor V gene specific primers, wherein the immune cell receptor J gene specific primers comprise a 3′ J gene hybridizing region and a 5′ second universal adapter region or hybridizing a plurality of immune cell receptor C gene specific primers to the C region portions of the extended immune cell receptor V gene specific primers, wherein the immune cell receptor C gene specific primers comprise a 3′ C gene hybridizing region and a 5′ second universal adapter region; and f) extending the hybridized immune cell receptor J gene specific primers or C gene specific primers with a polymerase, thereby forming a plurality of structurally different double-stranded products, each comprising at least a portion of the immune cell receptor V region, optionally the immune cell receptor D region, and at least a portion of the immune cell receptor J region or C region flanked by a first and second universal adapter sequence; g) amplifying the plurality of structurally different double-stranded products with thereby enriching the plurality of structurally different target polynucleotides comprising immune gene sequences; and h) determining nucleotide sequences of the plurality of structurally different target polynucleotides comprising the immune specific gene sequences from the products and claim 1 in U.S. Patent Number 11306356 is drawn to a method for enriching from a sample a plurality of structurally different target polynucleotides, wherein individual target polynucleotides of the plurality comprise immune cell receptor V, J, and C and optionally D gene regions, the method comprising: a) providing a reaction mixture comprising: i) the plurality of structurally different target polynucleotides; and ii) a plurality of immune cell receptor C gene specific primers, wherein the plurality of immune cell receptor C gene specific primers having the following regions from 5′ to 3′: [5′-Phos], [SPLINT], [BARCODE], and [FW], wherein: [5′-Phos] comprises a 5′ phosphate; [SPLINT] comprises an adaptor hybridization site of 2-8 nucleotides in length; [BARCODE] comprises a barcode region of at least 6 nucleotides in length, wherein each nucleotide of the barcode region is independently selected from the group consisting of N and W; and [FW] of each immune cell receptor C gene specific primer comprises a structurally distinct region that specifically hybridizes to an immune cell receptor C gene, wherein the immune cell receptor C gene specific primers are hybridized to the C gene regions of the target polynucleotides; b) extending the hybridized immune cell receptor C gene specific primers with a polymerase, and then removing un-extended immune cell receptor C gene specific primers, if present, wherein the extended immune cell receptor C gene specific primers comprise at least a portion of the immune cell receptor C region, optionally the immune cell receptor D region, at least a portion of the immune cell receptor J region, and at least a portion of the immune cell receptor V region; c) hybridizing a first universal adaptor to the [SPLINT] adaptor hybridization site of the extended immune cell receptor C gene specific primers, wherein said first universal adaptor is a double-stranded adaptor comprising a single-stranded overhang region that hybridizes to the [SPLINT] adaptor hybridization site of said extended primers; d) ligating the hybridized first universal adapters to the extended immune cell receptor C gene specific primers, and then removing un-ligated adapters, if present; e) hybridizing a plurality of immune cell receptor V gene specific primers to the V region portions of the extended immune cell receptor C gene specific primers, wherein the immune cell receptor V gene specific primers comprise a 3′ V gene hybridizing region and a 5′ second universal adapter region; and f) extending the hybridized immune cell receptor V gene specific primers with a polymerase, thereby forming a plurality of structurally different double-stranded products, each comprising at least a portion of the immune cell receptor V region, optionally the immune cell receptor D region, and at least a portion of the immune cell C region flanked by a first and second universal adapter sequence.
Therefore, the present claims are obvious in view of the claims of U.S. Patent Number 11306356.
Claims 1-4 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-10 of U.S. Patent Number 11725307.
Although the conflicting claims are not identical, they are not patentably distinct from each other because the present claim 1 is drawn to a method of quantifying immune specific genes in a pregnant woman carrying a fetus encoding an HPA-1a antigen, wherein the pregnant woman lacks the HPA-1a antigen, the method comprising, a) providing a reaction mixture comprising: i) a plurality of structurally different target polynucleotides from the pregnant woman, wherein individual target polynucleotides of the plurality comprise immune cell receptor V, J, and optionally C or D gene regions; and ii) a plurality of immune cell receptor V gene specific primers, wherein the immune cell receptor V gene specific primers comprise at least 10 structurally distinct primers having the following regions from 5′ to 3′: [5′-Phos], [SPLINT], [BARCODE], and [FW], wherein: [5′-Phos] comprises a 5′ phosphate; [SPLINT] comprises an adaptor hybridization site of 2-8 nucleotides in length; [BARCODE] comprises a barcode region of at least 6 nucleotides in length, wherein each nucleotide of the barcode region is independently selected from the group consisting of N and W; and [FW] of each immune cell receptor V gene specific primer comprises a structurally distinct region that specifically hybridizes to a framework 1, framework 2, or framework 3 region of an immune cell receptor V gene, wherein the immune cell receptor V gene specific primers are hybridized to the V gene regions of the target polynucleotides; b) extending the hybridized immune cell receptor V gene specific primers with a polymerase, and then removing un-extended immune cell receptor V gene specific primers, if present, wherein the extended immune cell receptor V gene specific primers comprise at least a portion of the immune cell receptor V region, optionally the immune cell receptor D region, at least a portion of the immune cell receptor C region, and at least a portion of the immune cell receptor J region; c) hybridizing a first universal adaptor to the [SPLINT] adaptor hybridization site of the extended immune cell receptor V gene specific primers, wherein said universal adaptor is a double-stranded adaptor, comprising: a 5′ single-stranded overhang region which can be hybridized to the SPLINT adaptor hybridization site of said extended primers; d) ligating the hybridized first universal adapters to the extended immune cell receptor V gene specific primers, and then removing un-ligated adapters, if present; e) hybridizing a plurality of immune cell receptor J gene specific primers to the J region portions of the extended immune cell receptor V gene specific primers, wherein the immune cell receptor J gene specific primers comprise a 3′ J gene hybridizing region and a 5′ second universal adapter region or hybridizing a plurality of immune cell receptor C gene specific primers to the C region portions of the extended immune cell receptor V gene specific primers, wherein the immune cell receptor C gene specific primers comprise a 3′ C gene hybridizing region and a 5′ second universal adapter region; and f) extending the hybridized immune cell receptor J gene specific primers or C gene specific primers with a polymerase, thereby forming a plurality of structurally different double-stranded products, each comprising at least a portion of the immune cell receptor V region, optionally the immune cell receptor D region, and at least a portion of the immune cell receptor J region or C region flanked by a first and second universal adapter sequence; g) amplifying the plurality of structurally different double-stranded products with thereby enriching the plurality of structurally different target polynucleotides comprising immune gene sequences; and h) determining nucleotide sequences of the plurality of structurally different target polynucleotides comprising the immune specific gene sequences from the products and claim 1 in U.S. Patent Number 11725307 is drawn to a method for enriching from a sample a plurality of structurally different target polynucleotides, the method comprising: a) providing a reaction mixture comprising: i) a plurality of structurally different target polynucleotides, wherein individual target polynucleotides of the plurality comprise immune cell receptor V, J, and optionally C or D gene regions; and ii) a plurality of immune cell receptor V gene specific primers, wherein the immune cell receptor V gene specific primers comprise at least 10 structurally distinct primers having the following regions from 5′ to 3′: [SPLINT], [BARCODE], and [FW], wherein: [SPLINT] comprises an adaptor hybridization site of 2-8 nucleotides in length; [BARCODE] comprises a barcode region of at least 6 nucleotides in length, wherein each nucleotide of the barcode region is independently selected from the group consisting of N and W; and [FW] of each immune cell receptor V gene specific primer comprises a structurally distinct region that specifically hybridizes to a framework 1, framework 2, or framework 3 region of an immune cell receptor V gene, wherein the immune cell receptor V gene specific primers are hybridized to the V gene regions of the target polynucleotides; b) extending the hybridized immune cell receptor V gene specific primers with a polymerase, and then removing un-extended immune cell receptor V gene specific primers, if present, wherein the extended immune cell receptor V gene specific primers comprise at least a portion of the immune cell receptor V region, optionally the immune cell receptor D region, at least a portion of the immune cell receptor C region, and at least a portion of the immune cell receptor J region; c) hybridizing a first universal adaptor to the [SPLINT] adaptor hybridization site of the extended immune cell receptor V gene specific primers; d) hybridizing a plurality of immune cell receptor J gene specific primers to the J region portions of the extended immune cell receptor V gene specific primers, wherein the immune cell receptor J gene specific primers comprise a 3′ J gene hybridizing region and a 5′ second universal adapter region or hybridizing a plurality of immune cell receptor C gene specific primers to the C region portions of the extended immune cell receptor V gene specific primers, wherein the immune cell receptor C gene specific primers comprise a 3′ C gene hybridizing region and a 5′ second universal adapter region; and e) extending the hybridized immune cell receptor J gene specific primers or C gene specific primers with a polymerase, thereby forming a plurality of structurally different double-stranded products, each comprising at least a portion of the immune cell receptor V region, optionally the immune cell receptor D region, and at least a portion of the immune cell receptor J region or C region flanked by a first and second universal adapter sequence.
Therefore, the present claims are obvious in view of the claims of U.S. Patent Number 11725307.
Claims 1-4 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-19 of U.S. Patent Number 11773511.
Although the conflicting claims are not identical, they are not patentably distinct from each other because the present claim 1 is drawn to a method of quantifying immune specific genes in a pregnant woman carrying a fetus encoding an HPA-1a antigen, wherein the pregnant woman lacks the HPA-1a antigen, the method comprising, a) providing a reaction mixture comprising: i) a plurality of structurally different target polynucleotides from the pregnant woman, wherein individual target polynucleotides of the plurality comprise immune cell receptor V, J, and optionally C or D gene regions; and ii) a plurality of immune cell receptor V gene specific primers, wherein the immune cell receptor V gene specific primers comprise at least 10 structurally distinct primers having the following regions from 5′ to 3′: [5′-Phos], [SPLINT], [BARCODE], and [FW], wherein: [5′-Phos] comprises a 5′ phosphate; [SPLINT] comprises an adaptor hybridization site of 2-8 nucleotides in length; [BARCODE] comprises a barcode region of at least 6 nucleotides in length, wherein each nucleotide of the barcode region is independently selected from the group consisting of N and W; and [FW] of each immune cell receptor V gene specific primer comprises a structurally distinct region that specifically hybridizes to a framework 1, framework 2, or framework 3 region of an immune cell receptor V gene, wherein the immune cell receptor V gene specific primers are hybridized to the V gene regions of the target polynucleotides; b) extending the hybridized immune cell receptor V gene specific primers with a polymerase, and then removing un-extended immune cell receptor V gene specific primers, if present, wherein the extended immune cell receptor V gene specific primers comprise at least a portion of the immune cell receptor V region, optionally the immune cell receptor D region, at least a portion of the immune cell receptor C region, and at least a portion of the immune cell receptor J region; c) hybridizing a first universal adaptor to the [SPLINT] adaptor hybridization site of the extended immune cell receptor V gene specific primers, wherein said universal adaptor is a double-stranded adaptor, comprising: a 5′ single-stranded overhang region which can be hybridized to the SPLINT adaptor hybridization site of said extended primers; d) ligating the hybridized first universal adapters to the extended immune cell receptor V gene specific primers, and then removing un-ligated adapters, if present; e) hybridizing a plurality of immune cell receptor J gene specific primers to the J region portions of the extended immune cell receptor V gene specific primers, wherein the immune cell receptor J gene specific primers comprise a 3′ J gene hybridizing region and a 5′ second universal adapter region or hybridizing a plurality of immune cell receptor C gene specific primers to the C region portions of the extended immune cell receptor V gene specific primers, wherein the immune cell receptor C gene specific primers comprise a 3′ C gene hybridizing region and a 5′ second universal adapter region; and f) extending the hybridized immune cell receptor J gene specific primers or C gene specific primers with a polymerase, thereby forming a plurality of structurally different double-stranded products, each comprising at least a portion of the immune cell receptor V region, optionally the immune cell receptor D region, and at least a portion of the immune cell receptor J region or C region flanked by a first and second universal adapter sequence; g) amplifying the plurality of structurally different double-stranded products with thereby enriching the plurality of structurally different target polynucleotides comprising immune gene sequences; and h) determining nucleotide sequences of the plurality of structurally different target polynucleotides comprising the immune specific gene sequences from the products and claim 1 in U.S. Patent Number 11773511 is drawn to a method for enriching a sample for a plurality of structurally different target polynucleotides comprising an immune gene sequence the method comprising: a) contacting a sample with a plurality of immune cell receptor V gene specific primers, each primer including from 5′ to 3′: [SPLINT1], [BARCODE], and [V], wherein: [SPLINT] is a first adaptor sequence; [BARCODE] is a unique molecular identifier barcode; and [V] is a sequence capable of hybridizing to an immune cell receptor V gene; b) hybridizing and extending the V gene specific primers to form a plurality of first double-stranded primer extension products; c) contacting the sample with an exonuclease to remove unhybridized V gene specific primers from the first double stranded primer extension products; d) contacting the sample with a plurality of immune cell receptor J gene specific primers, each primer including from 5′ to 3′: [SPLINT2], and [J], wherein: [SPLINT2] is a second adaptor sequence; and [J] is a sequence capable of hybridizing to an immune cell receptor J gene; and further contacting the sample with a first universal primer capable of hybridizing to the first adaptor sequence; e) hybridizing and extending the J gene specific primers and the first universal primer to form a plurality of second double-stranded primer extension products; f) contacting the sample with an exonuclease to remove unhybridized J gene specific primers and first universal primer from the second double-stranded primer extension products; g) contacting the sample with first and second universal primers capable of hybridizing to the first and second adaptor sequences; h) amplifying the plurality of second double-stranded primer extension products thereby enriching the plurality of structurally different target polynucleotides comprising an immune gene sequence.
Therefore, the present claims are obvious in view of the claims of U.S. Patent Number 11773511.
Claims 1-4 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-20 of U.S. Patent Number 12043919.
Although the conflicting claims are not identical, they are not patentably distinct from each other because the present claim 1 is drawn to a method of quantifying immune specific genes in a pregnant woman carrying a fetus encoding an HPA-1a antigen, wherein the pregnant woman lacks the HPA-1a antigen, the method comprising, a) providing a reaction mixture comprising: i) a plurality of structurally different target polynucleotides from the pregnant woman, wherein individual target polynucleotides of the plurality comprise immune cell receptor V, J, and optionally C or D gene regions; and ii) a plurality of immune cell receptor V gene specific primers, wherein the immune cell receptor V gene specific primers comprise at least 10 structurally distinct primers having the following regions from 5′ to 3′: [5′-Phos], [SPLINT], [BARCODE], and [FW], wherein: [5′-Phos] comprises a 5′ phosphate; [SPLINT] comprises an adaptor hybridization site of 2-8 nucleotides in length; [BARCODE] comprises a barcode region of at least 6 nucleotides in length, wherein each nucleotide of the barcode region is independently selected from the group consisting of N and W; and [FW] of each immune cell receptor V gene specific primer comprises a structurally distinct region that specifically hybridizes to a framework 1, framework 2, or framework 3 region of an immune cell receptor V gene, wherein the immune cell receptor V gene specific primers are hybridized to the V gene regions of the target polynucleotides; b) extending the hybridized immune cell receptor V gene specific primers with a polymerase, and then removing un-extended immune cell receptor V gene specific primers, if present, wherein the extended immune cell receptor V gene specific primers comprise at least a portion of the immune cell receptor V region, optionally the immune cell receptor D region, at least a portion of the immune cell receptor C region, and at least a portion of the immune cell receptor J region; c) hybridizing a first universal adaptor to the [SPLINT] adaptor hybridization site of the extended immune cell receptor V gene specific primers, wherein said universal adaptor is a double-stranded adaptor, comprising: a 5′ single-stranded overhang region which can be hybridized to the SPLINT adaptor hybridization site of said extended primers; d) ligating the hybridized first universal adapters to the extended immune cell receptor V gene specific primers, and then removing un-ligated adapters, if present; e) hybridizing a plurality of immune cell receptor J gene specific primers to the J region portions of the extended immune cell receptor V gene specific primers, wherein the immune cell receptor J gene specific primers comprise a 3′ J gene hybridizing region and a 5′ second universal adapter region or hybridizing a plurality of immune cell receptor C gene specific primers to the C region portions of the extended immune cell receptor V gene specific primers, wherein the immune cell receptor C gene specific primers comprise a 3′ C gene hybridizing region and a 5′ second universal adapter region; and f) extending the hybridized immune cell receptor J gene specific primers or C gene specific primers with a polymerase, thereby forming a plurality of structurally different double-stranded products, each comprising at least a portion of the immune cell receptor V region, optionally the immune cell receptor D region, and at least a portion of the immune cell receptor J region or C region flanked by a first and second universal adapter sequence; g) amplifying the plurality of structurally different double-stranded products with thereby enriching the plurality of structurally different target polynucleotides comprising immune gene sequences; and h) determining nucleotide sequences of the plurality of structurally different target polynucleotides comprising the immune specific gene sequences from the products and claim 1 in U.S. Patent Number 12043919 is drawn to a method for enriching a sample for a plurality of structurally different target polynucleotides comprising an immune gene sequence the method comprising: a) contacting a sample with a plurality of immune cell receptor J gene specific primers, the immune cell receptor J gene specific primers comprising from 5′ to 3′: [SPLINT1], [BARCODE], and [J], wherein: [SPLINT1] is a first adaptor sequence; [BARCODE] is a unique molecular identifier barcode; and [J] is a sequence capable of hybridizing to an immune cell receptor J gene; b) hybridizing and extending the J gene specific primers to form a plurality of first primer extension products; c) removing unhybridized J gene specific primers from the first primer extension products; d) contacting the first primer extension products with a plurality of immune cell receptor V gene specific primers, wherein the immune cell receptor V gene specific primers comprise from 5′ to 3′: [SPLINT2], and [J V], wherein: [SPLINT2] is a second adaptor sequence; and [V] is a sequence capable of hybridizing to an immune cell receptor V gene; e) hybridizing and extending the V gene specific primers to form a plurality of second primer extension products; f) removing unhybridized V gene specific primers from the second primer extension products; g) contacting the sample with first and second universal primers that hybridize to the first and second adaptor sequences; h) amplifying the plurality of first and second primer extension products with the first and second universal primers, thereby enriching the plurality of structurally different target polynucleotides comprising an immune gene sequence.
Therefore, the present claims are obvious in view of the claims of U.S. Patent Number 12043919.
Claims 1-4 are provisionally rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-38 of copending Application Number 18449216.
Although the conflicting claims are not identical, they are not patentably distinct from each other because the present claim 1 is drawn to a method of quantifying immune specific genes in a pregnant woman carrying a fetus encoding an HPA-1a antigen, wherein the pregnant woman lacks the HPA-1a antigen, the method comprising, a) providing a reaction mixture comprising: i) a plurality of structurally different target polynucleotides from the pregnant woman, wherein individual target polynucleotides of the plurality comprise immune cell receptor V, J, and optionally C or D gene regions; and ii) a plurality of immune cell receptor V gene specific primers, wherein the immune cell receptor V gene specific primers comprise at least 10 structurally distinct primers having the following regions from 5′ to 3′: [5′-Phos], [SPLINT], [BARCODE], and [FW], wherein: [5′-Phos] comprises a 5′ phosphate; [SPLINT] comprises an adaptor hybridization site of 2-8 nucleotides in length; [BARCODE] comprises a barcode region of at least 6 nucleotides in length, wherein each nucleotide of the barcode region is independently selected from the group consisting of N and W; and [FW] of each immune cell receptor V gene specific primer comprises a structurally distinct region that specifically hybridizes to a framework 1, framework 2, or framework 3 region of an immune cell receptor V gene, wherein the immune cell receptor V gene specific primers are hybridized to the V gene regions of the target polynucleotides; b) extending the hybridized immune cell receptor V gene specific primers with a polymerase, and then removing un-extended immune cell receptor V gene specific primers, if present, wherein the extended immune cell receptor V gene specific primers comprise at least a portion of the immune cell receptor V region, optionally the immune cell receptor D region, at least a portion of the immune cell receptor C region, and at least a portion of the immune cell receptor J region; c) hybridizing a first universal adaptor to the [SPLINT] adaptor hybridization site of the extended immune cell receptor V gene specific primers, wherein said universal adaptor is a double-stranded adaptor, comprising: a 5′ single-stranded overhang region which can be hybridized to the SPLINT adaptor hybridization site of said extended primers; d) ligating the hybridized first universal adapters to the extended immune cell receptor V gene specific primers, and then removing un-ligated adapters, if present; e) hybridizing a plurality of immune cell receptor J gene specific primers to the J region portions of the extended immune cell receptor V gene specific primers, wherein the immune cell receptor J gene specific primers comprise a 3′ J gene hybridizing region and a 5′ second universal adapter region or hybridizing a plurality of immune cell receptor C gene specific primers to the C region portions of the extended immune cell receptor V gene specific primers, wherein the immune cell receptor C gene specific primers comprise a 3′ C gene hybridizing region and a 5′ second universal adapter region; and f) extending the hybridized immune cell receptor J gene specific primers or C gene specific primers with a polymerase, thereby forming a plurality of structurally different double-stranded products, each comprising at least a portion of the immune cell receptor V region, optionally the immune cell receptor D region, and at least a portion of the immune cell receptor J region or C region flanked by a first and second universal adapter sequence; g) amplifying the plurality of structurally different double-stranded products with thereby enriching the plurality of structurally different target polynucleotides comprising immune gene sequences; and h) determining nucleotide sequences of the plurality of structurally different target polynucleotides comprising the immune specific gene sequences from the products and claim 1 in copending Application Number 18449216 is drawn to a method for enriching a sample for a plurality of structurally different target polynucleotides comprising an immune gene sequence the method comprising: a) contacting a sample with a plurality of immune cell receptor V gene specific primers, each primer including from 5′ to 3′: [5′-Phos], [SPLINT1], [BARCODE], and [V], wherein: [5′-Phos] is a 5′ phosphate; [SPLINT] is a first adaptor sequence; [BARCODE] is a unique molecular identifier barcode; and [V] is a sequence capable of hybridizing to an immune cell receptor V gene; b) hybridizing and extending the V gene specific primers to form a plurality of first double-stranded primer extension products; c) contacting the sample with an exonuclease to remove unhybridized V gene specific primers from the first double stranded primer extension products; d) contacting the sample with a plurality of immune cell receptor J gene specific primers, each primer including from 5′ to 3′: [5′-Phos], [SPLINT2], and [J], wherein: [5′-Phos] is a 5′ phosphate; [SPLINT2] is a second adaptor sequence; and [J] is a sequence capable of hybridizing to an immune cell receptor J gene; and further contacting the sample with a first universal primer capable of hybridizing to the first adaptor sequence; e) hybridizing and extending the J gene specific primers and the first universal primer to form a plurality of second double-stranded primer extension products; f) contacting the sample with an exonuclease to remove unhybridized J gene specific primers and first universal primer from the second double-stranded primer extension products; g) contacting the sample with first and second universal primers capable of hybridizing to the first and second adaptor sequences; h) amplifying the plurality of second double-stranded primer extension products thereby enriching the plurality of structurally different target polynucleotides comprising an immune gene sequence.
Therefore, the present claims are obvious in view of the claims of the copending Application Number 18449216.
This is a provisional obviousness-type double patenting rejection because the conflicting claims have not in fact been patented.
Claims 1-4 are provisionally rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 11-19 of copending Application Number 18215555.
Although the conflicting claims are not identical, they are not patentably distinct from each other because the present claim 1 is drawn to a method of quantifying immune specific genes in a pregnant woman carrying a fetus encoding an HPA-1a antigen, wherein the pregnant woman lacks the HPA-1a antigen, the method comprising, a) providing a reaction mixture comprising: i) a plurality of structurally different target polynucleotides from the pregnant woman, wherein individual target polynucleotides of the plurality comprise immune cell receptor V, J, and optionally C or D gene regions; and ii) a plurality of immune cell receptor V gene specific primers, wherein the immune cell receptor V gene specific primers comprise at least 10 structurally distinct primers having the following regions from 5′ to 3′: [5′-Phos], [SPLINT], [BARCODE], and [FW], wherein: [5′-Phos] comprises a 5′ phosphate; [SPLINT] comprises an adaptor hybridization site of 2-8 nucleotides in length; [BARCODE] comprises a barcode region of at least 6 nucleotides in length, wherein each nucleotide of the barcode region is independently selected from the group consisting of N and W; and [FW] of each immune cell receptor V gene specific primer comprises a structurally distinct region that specifically hybridizes to a framework 1, framework 2, or framework 3 region of an immune cell receptor V gene, wherein the immune cell receptor V gene specific primers are hybridized to the V gene regions of the target polynucleotides; b) extending the hybridized immune cell receptor V gene specific primers with a polymerase, and then removing un-extended immune cell receptor V gene specific primers, if present, wherein the extended immune cell receptor V gene specific primers comprise at least a portion of the immune cell receptor V region, optionally the immune cell receptor D region, at least a portion of the immune cell receptor C region, and at least a portion of the immune cell receptor J region; c) hybridizing a first universal adaptor to the [SPLINT] adaptor hybridization site of the extended immune cell receptor V gene specific primers, wherein said universal adaptor is a double-stranded adaptor, comprising: a 5′ single-stranded overhang region which can be hybridized to the SPLINT adaptor hybridization site of said extended primers; d) ligating the hybridized first universal adapters to the extended immune cell receptor V gene specific primers, and then removing un-ligated adapters, if present; e) hybridizing a plurality of immune cell receptor J gene specific primers to the J region portions of the extended immune cell receptor V gene specific primers, wherein the immune cell receptor J gene specific primers comprise a 3′ J gene hybridizing region and a 5′ second universal adapter region or hybridizing a plurality of immune cell receptor C gene specific primers to the C region portions of the extended immune cell receptor V gene specific primers, wherein the immune cell receptor C gene specific primers comprise a 3′ C gene hybridizing region and a 5′ second universal adapter region; and f) extending the hybridized immune cell receptor J gene specific primers or C gene specific primers with a polymerase, thereby forming a plurality of structurally different double-stranded products, each comprising at least a portion of the immune cell receptor V region, optionally the immune cell receptor D region, and at least a portion of the immune cell receptor J region or C region flanked by a first and second universal adapter sequence; g) amplifying the plurality of structurally different double-stranded products with thereby enriching the plurality of structurally different target polynucleotides comprising immune gene sequences; and h) determining nucleotide sequences of the plurality of structurally different target polynucleotides comprising the immune specific gene sequences from the products and claim 11 in copending Application Number 18215555 is drawn to a method for enriching from a sample a plurality of structurally different target polynucleotides, wherein individual target polynucleotides of the plurality comprise immune cell receptor V, and J gene regions, the method comprising: a) providing a reaction mixture comprising: i) the plurality of structurally different target polynucleotides; and ii) a plurality of immune cell receptor J gene specific primers, wherein the plurality of immune cell receptor J gene specific primers having the following regions from 5′ to 3′: [5′-Phos], [SPLINT], [BARCODE], and [FW], wherein: [5′-Phos] comprises a 5′ phosphate; [SPLINT] comprises an adaptor hybridization site of 2-8 nucleotides in length; [BARCODE] comprises a barcode region of at least 6 nucleotides in length, wherein each nucleotide of the barcode region is independently selected from the group consisting of N and W; and [FW] of each immune cell receptor J gene specific primer comprises a structurally distinct region that specifically hybridizes to an immune cell receptor J gene, wherein the immune cell receptor J gene specific primers are hybridized to the J gene regions of the target polynucleotides; b) extending the hybridized immune cell receptor J gene specific primers with a polymerase, and then removing un-extended immune cell receptor J gene specific primers, if present, wherein the extended immune cell receptor J gene specific primers comprise at least a portion of the immune cell receptor J region and at least a portion of the immune cell receptor V region; c) hybridizing a first universal adaptor to the [SPLINT] adaptor hybridization site of the extended immune cell receptor J gene specific primers, wherein said first universal adaptor is a double-stranded adaptor comprising a single-stranded overhang region that hybridizes to the [SPLINT] adaptor hybridization site of said extended primers; d) ligating the hybridized first universal adapters to the extended immune cell receptor J gene specific primers, and then removing un-ligated adapters, if present; e) hybridizing a plurality of immune cell receptor V gene specific primers to the V region portions of the extended immune cell receptor C gene specific primers, wherein the immune cell receptor V gene specific primers comprise a 3′ V gene hybridizing region and a 5′ second universal adapter region; and f) extending the hybridized immune cell receptor V gene specific primers with a polymerase, thereby forming a plurality of structurally different double-stranded products, each comprising at least a portion of the immune cell receptor V region and at least a portion of the immune cell J region flanked by a first and second universal adapter sequence.
Therefore, the present claims are obvious in view of the claims of the copending Application Number 18215555.
This is a provisional obviousness-type double patenting rejection because the conflicting claims have not in fact been patented.
Claims 1-4 are provisionally rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 39-55 of copending Application Number 18741007.
Although the conflicting claims are not identical, they are not patentably distinct from each other because the present claim 1 is drawn to a method of quantifying immune specific genes in a pregnant woman carrying a fetus encoding an HPA-1a antigen, wherein the pregnant woman lacks the HPA-1a antigen, the method comprising, a) providing a reaction mixture comprising: i) a plurality of structurally different target polynucleotides from the pregnant woman, wherein individual target polynucleotides of the plurality comprise immune cell receptor V, J, and optionally C or D gene regions; and ii) a plurality of immune cell receptor V gene specific primers, wherein the immune cell receptor V gene specific primers comprise at least 10 structurally distinct primers having the following regions from 5′ to 3′: [5′-Phos], [SPLINT], [BARCODE], and [FW], wherein: [5′-Phos] comprises a 5′ phosphate; [SPLINT] comprises an adaptor hybridization site of 2-8 nucleotides in length; [BARCODE] comprises a barcode region of at least 6 nucleotides in length, wherein each nucleotide of the barcode region is independently selected from the group consisting of N and W; and [FW] of each immune cell receptor V gene specific primer comprises a structurally distinct region that specifically hybridizes to a framework 1, framework 2, or framework 3 region of an immune cell receptor V gene, wherein the immune cell receptor V gene specific primers are hybridized to the V gene regions of the target polynucleotides; b) extending the hybridized immune cell receptor V gene specific primers with a polymerase, and then removing un-extended immune cell receptor V gene specific primers, if present, wherein the extended immune cell receptor V gene specific primers comprise at least a portion of the immune cell receptor V region, optionally the immune cell receptor D region, at least a portion of the immune cell receptor C region, and at least a portion of the immune cell receptor J region; c) hybridizing a first universal adaptor to the [SPLINT] adaptor hybridization site of the extended immune cell receptor V gene specific primers, wherein said universal adaptor is a double-stranded adaptor, comprising: a 5′ single-stranded overhang region which can be hybridized to the SPLINT adaptor hybridization site of said extended primers; d) ligating the hybridized first universal adapters to the extended immune cell receptor V gene specific primers, and then removing un-ligated adapters, if present; e) hybridizing a plurality of immune cell receptor J gene specific primers to the J region portions of the extended immune cell receptor V gene specific primers, wherein the immune cell receptor J gene specific primers comprise a 3′ J gene hybridizing region and a 5′ second universal adapter region or hybridizing a plurality of immune cell receptor C gene specific primers to the C region portions of the extended immune cell receptor V gene specific primers, wherein the immune cell receptor C gene specific primers comprise a 3′ C gene hybridizing region and a 5′ second universal adapter region; and f) extending the hybridized immune cell receptor J gene specific primers or C gene specific primers with a polymerase, thereby forming a plurality of structurally different double-stranded products, each comprising at least a portion of the immune cell receptor V region, optionally the immune cell receptor D region, and at least a portion of the immune cell receptor J region or C region flanked by a first and second universal adapter sequence; g) amplifying the plurality of structurally different double-stranded products with thereby enriching the plurality of structurally different target polynucleotides comprising immune gene sequences; and h) determining nucleotide sequences of the plurality of structurally different target polynucleotides comprising the immune specific gene sequences from the products and claim 39 in copending Application Number 18741007 is drawn to a method for enriching a sample for a plurality of structurally different target polynucleotides comprising an immune gene sequence, the method comprising: a) contacting a sample with a plurality of immune cell receptor C gene specific primers, the immune cell receptor C gene specific primers comprising from 5′ to 3′: [SPLINT1], [BARCODE], and [C], wherein: [SPLINT1] is a first adaptor sequence; [BARCODE] is a unique molecular identifier barcode; and [C] is a sequence capable of hybridizing to an immune cell receptor C gene; b) hybridizing and extending the C gene specific primers to form a plurality of first primer extension products; c) contacting the first primer extension products with a plurality of immune cell receptor V gene specific primers, wherein the immune cell receptor V gene specific primers comprise from 5′ to 3′: [SPLINT2], and [V], wherein: [SPLINT2] is a second adaptor sequence; and [V] is a sequence capable of hybridizing to an immune cell receptor V gene; d) hybridizing and extending the V gene specific primers to form a plurality of second primer extension products; e) removing unhybridized V gene specific primers from the second primer extension products; f) contacting the sample with first and second universal primers that hybridize to the first and second adaptor sequences; g) amplifying the plurality of first and second primer extension products with the first and second universal primers, thereby enriching the plurality of structurally different target polynucleotides comprising an immune gene sequence.
Therefore, the present claims are obvious in view of the claims of the copending Application Number 18741007.
This is a provisional obviousness-type double patenting rejection because the conflicting claims have not in fact been patented.
Conclusion
No claim is allowed.
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/CHRISTIAN C BOESEN/Primary Examiner, Art Unit 1684