Status of the Claims
Claim 1-15 are currently pending and examined herein.
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Interpretation
The recitation of “during the preparation of a target capture region” of the instant claim 1 (lines 3-4, 6-7, 9-10, and 12-13) is a recitation of intended use of the instant claimed blocker and a recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. Furthermore, as per MPEP § 2115, “[i]nclusion of material or article worked upon by a structure being claimed does not impart patentability to the claims.” In re Young, 75 F.2d 996, 25 USPQ 69 (CCPA 1935) (as restated in In re Otto, 312 F.2d 937, 136 USPQ 458, 459 (CCPA 1963)), and that the manner or method in which a machine is to be utilized is not germane to the issue of patentability of the machine itself.
The preamble of claim 6 recites a “kit.” The specification, however, does not define this term, and so it is being interpreted to encompass any collection of reagents that includes all of the elements of the claims. Any further interpretation of the word is considered an “intended use” and does not impart any further structural limitation of on the claimed subject matter. Furthermore, the recited components of the “kit” only include the blocker of claim 1. Therefore, a collection of reagents that includes, at a minimum, the blocker of claim 1, would meet claim 6.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 8-13 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 8 recites the limitation "the sample". There is insufficient antecedent basis for this limitation in the claim. Claims 9 and 10 are similarly rejected as they depend on claim 8.
Claim 11 recites the limitation “fragmenting sequences of a sample”. The term “sequences” here is unclear as a sequence is an abstraction and a “sequence of a sample” is so broad as to where the metes and bounds of the limitation cannot be determined. Claims 12 and 13 are similarly rejected as they depend on claim 11. For purposes of examination, this limitation will be interpreted as “fragmenting nucleic acids of a sample”. This rejection may be overcome by replacing “sequences” with a term such as “nucleic acids” or the like. Other solutions are possible.
Claim 12 recites the limitation “the capture kit”. There is insufficient antecedent basis for this limitation in the claim because “a capture kit” is not recited in claim 12 nor in claim 11, upon which claim 12 depends.
Claim 13 recites the limitation “the molar ratio of the blockers to the sequences”. As “blocker” refers to both the individual blockers 1-4 and the set of blockers 1-4, it is unclear whether the recited molar ratios are ratios of each blocker to the sequences, or the ratio of all blockers to the sequences. In other words, whether the ratio is (150 moles blocker 1: 1 mole sequences) or (150 moles of blockers 1-4: 1 mole of sequences).
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1 and 3-15 are rejected under 35 U.S.C. 103 as being unpatentable over Gunning (PGPub No: US 2022/0282398).
Regarding claims 1 and 6, Gunning discloses a blocker (Fig. 3) comprising blocker 1 (“E”) that is complementary to a sequence of sequencing adapter P5 (“1st extension primer-binding site”), blocker 2 (“G”) that is complementary to a sequence of Rsp1’ (“C of 1st sequencing primer-binding site”), blocker 3 (“I”) that is partially complementary to a sequence of Rsp2 (“2nd sequencing primer-binding site”), and blocker 4 (“F”) that is complementary to a sequence of sequencing adapter P7’ (C of 2nd extension primer-binding site”). Additionally, blockers 1 and 3 block the first strand while blockers 2 and 4 block the second strand. Gunning further discloses the inverse of this arrangement (p. 17, ¶[0136]) where blockers 1 and 3 block the second strand while blockers 2 and 4 block the first strand. Therefore, blockers 1-4 as described in the instant claim are all disclosed by Gunning.
However, Gunning does not disclose a set of blockers where blockers 1 and 2 block the first strand and blockers 3 and 4 block the second strand. In other words, though Gunning discloses blockers 1-4, it does not disclose a blocker comprising blockers 1-4 in a coherent set. Therefore, the difference between Gunning and the instant claim is a matter of the arrangement of the blockers in terms of which strands they are configured to block.
According to MPEP 2144.04(VI)(C), the courts have ruled that rearrangement of parts is considered a routine expedience available to one of ordinary skill in the art (In re Japikse, 181 F.2d 1019, 86 USPQ 70 (CCPA 1950); In re Kuhle, 526 F.2d 553, 188 USPQ 7 (CCPA 1975)). Based on this rationale and because Gunning teaches each of blockers 1-4, it would have been obvious to one of ordinary skill in the art by the effective filing date to rearrange the set of blockers to include blockers 1-4 in a single set.
Regarding claims 3-5, Gunning discloses (Table I; p. 19, ¶[0139]) that blocker 1 is 29 bases in length and comprises the sequence set forth in SEQ ID No. 1 (Table I, SEQ ID NO: 6); blocker 2 is 32 bases in length and comprises all but one nucleotide of the sequence set forth in SEQ ID No. 2 (Table I, SEQ ID NO: 8); blocker 3 is complementary to the Rsp2’ sequence from the first base at the 5’ end, to the 27th base at the 3’ end, is 33 bases in length and comprises the sequences set forth in SEQ ID Nos. 3 and 43 (Table I, SEQ ID NO: 4); and blocker 4 is 24 bases in length and comprises the sequence set forth in SEQ ID No. 4 (Table I, SEQ ID NO: 2). The differences between Gunning and the instant claims are that, in the disclosure of Gunning, blocker 1 is one nucleotide longer, blocker 2 is one nucleotide shorter, and blocker 3 is 6 nucleotides longer.
Regarding blockers 1 and 2, a difference of one nucleotide is close to the claimed length of these blockers. According to MPEP 2144.05(I): “a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close.” Therefore, the lengths of blockers 1 and 2 and the sequence of blocker 2 are rendered obvious by the disclosure of Gunning.
Regarding blocker 3, Gunning also teaches that the length of the blocker is not required to be the same length as its target sequence, and only must have a length sufficient to block the target sequence when hybridized (p. 8. ¶[0053]). Additionally, Gunning teaches that a blocker can be a nucleotide having a length from 5 to 60 bases (p. 7, ¶[0049]). Similar to the above discussion, MPEP 2144.05(I) also states that ranges or amounts that “lie inside ranges disclosed by the prior art” are also prima facie obvious. As a length of 27 bases lies within the range disclosed by Gunning, it would have been obvious to one of ordinary skill in the art by the effective filing date to decrease the length of blocker 3 of Gunning to that of the instant claim.
Regarding claims 7, 11, 14, and 15, Gunning discloses a method for constructing a target region capture library comprising fragmenting sequences of a sample (p. 13, ¶[0101]); preparing a pre-library (p.13, ¶[0102]); preparing/capturing the target region capture library from the pre-library using the blocker/capture kit (p. 21, ¶[0163]); and performing PCR on the target region capture library to obtain a sequencing library (p. 21, ¶[0172, 5]).
Regarding claims 8, Gunning discloses the limitations of claim 7 and fragmenting the sample, as discussed above. Additionally, Gunning discloses that the fragments have a size typically in the range of 200 to 500 base pairs and that the fragment size can be adjusted for the sequencing platform being used (p. 13, ¶[0101]). Gunning does not disclose that the fragments have an average length ranging from 200 to 250 base pairs, but this range of the instant claim lies within the range provided by Gunning, rendering the average fragment length obvious per MPEP 2144.05(I) as discussed previously.
Regarding claims 9 and 10, Gunning further discloses subjecting the fragments to pre-library preparation (p. 13, ¶[0101]: “the fragments can be treated…”) and adding an index sequence to the fragments (p. 13, ¶[0102]).
Regarding claim 12, Gunning discloses the limitations of claim 11 as discussed above and fragmenting to an average length of 200 to 250 base pairs is obvious as discussed regarding claim 8. Gunning additionally discloses adding an index (p. 13, ¶[0102); blocking the fragments using the blockers (p. 21, ¶[0160]); and performing PCR on the sequences blocked to obtain the sequencing library (p. 21, ¶[0172, 5]).
Regarding claim 13, Gunning discloses that the molar ratio of the blockers to the sequences in the pre-library can be (25:1) or greater and that the ratio of blocker to target is chosen to reduce off-target capture (p. 12, ¶[0090]). Gunning does not teach that the molar ratio is (150:1) to (160:1). However, MPEP 2144.05(II)(A) states that: “differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical.” See also In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955); Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382; In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969); Merck & Co. Inc. v. Biocraft Lab. Inc., 874 F.2d 804, 809, 10 USPQ2d 1843, 1848 (Fed. Cir. 1989), cert. denied, 493 U.S. 975 (1989) and In re Williams, 36 F.2d 436, 438, 4 USPQ 237 (CCPA 1929). In the absence of evidence of criticality, changes in concentration such as a change in molar ratio of components is prima facie obvious, rendering claim 13 obvious over the teachings of Gunning.
Claim 2 is rejected under 35 U.S.C. 103 as being unpatentable over Gunning in view of Slatter et al. (PGPub No: US 2021/0164027).
Regarding claim 2, Gunning discloses (Table I; p. 19, ¶[0139]) that blockers 1 (SEQ ID NO: 6) and 4 (SEQ ID NO: 2) comprise locked nucleic acids. Gunning does not disclose that the locked nucleic acids are at position 25 from the 5’ end for blocker 1 and position 22 from the 5’ end for blocker 4. However, Gunning does teach that blockers may comprise locked nucleic acids to increase the Tm of the blocker-adapter duplex (p. 10, ¶[0070-2], that the Tm of this interaction is ideally higher than the annealing temperature (p. 12, ¶[0089], lines 14-18), and that the annealing temperature depends on several factors (p. 12, ¶[0089], lines 1-9). These teachings indicate that the Tm of the blocker-adapter duplex may need to be adjusted based on the experimental conditions, and that one way to do so is by incorporating locked nucleic acids, making the incorporation of locked nucleic acids into a sequence a result-effective variable. Adjusting a result-effective variable is routine optimization and therefore obvious to one of ordinary skill in the art in the absence of evidence of criticality (see MPEP 2144.05(II)). As such, it would have been obvious to one of ordinary skill in the art before the effective filing date to incorporate a locked nucleic acid in position 25 of blocker 1 and positions 20 and 22 of blocker 4 by routine optimization.
Gunning also does not disclose that blockers 2 and 3 comprise reverse dT modifications at the 3’ end. However, Gunning teaches that the 3’ ends of the blockers can be modified in order to prevent polymerase extension from this end during a later PCR step, and that 3’ end modifications are known in the art (p. 11, ¶[0080]). Slatter teaches that a reverse dT modification is a 3’ terminal group that prevents polymerase extension (p. 8, ¶[0074]). Therefore, it would have been obvious to one of ordinary skill in the art by the effective filing date to incorporate the reverse dT modification taught by Slatter into the blockers of Gunning, based on the motivation to prevent polymerase extension from the blockers during downstream steps. Additionally, there would have been a reasonable expectation of success in doing so because Slatter teaches that these reverse dT modifications can be incorporated into blockers (p. 8, ¶[0074]).
Conclusion
No claims are allowed.
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/ALEXANDRA OLSON/Examiner, Art Unit 1684
/JEREMY C FLINDERS/Primary Examiner, Art Unit 1684
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