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
Status of the Claims
Claims 1-13 are pending and the subject of this NON-FINAL Office Action. This is the first action on the merits.
Claim Rejection - 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 1-8 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more.
Specifically, the claims are directed to the natural sequences of HLA genes which are not markedly different from products of nature.
First, under Step 1, the claims are directed to a primer product. Thus, the claims are directed to statutory methods.
However, under markedly different analysis, the primers are natural sequences. See MPEP §§ 2106.04(b)(II) & (c). The primers directed to HLA genes are not markedly different from a natural sequence because no other additional elements are recited (e.g. label). Natural sequence perform the same functions in nature as they do in primers. Moreover, the molar ratios do not change the sequences themselves, or the functions thereof. Nor does the inclusion of other generic natural components (PCR amplification reagent such as water, polymerase etc.; sequencing library construction reagent such as generic sequence of adaptor that reads on a natural sequence, ligase, etc.; or gene purification reagent such as natural buffers, water, etc.) into a kit of parts, separately packaged.
Claim Rejections - 35 USC § 112- Indefiniteness
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.
Claims 1-13 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
The metes and bounds of the claims are so unclear and confusing that the Office cannot determine if the instant claims are patentable because it would require the Office to speculate as to the metes and bounds of the instant claims. See MPEP § 2173.06 (“Second, where there is a great deal of confusion and uncertainty as to the proper interpretation of the limitations of a claim, it would not be proper to reject such a claim on the basis of prior art. As stated in In re Steele, 305 F.2d 859, 134 USPQ 292 (CCPA 1962), a rejection under 35 U.S.C. 103 should not be based on considerable speculation about the meaning of terms employed in a claim or assumptions that must be made as to the scope of the claims.”). Specifically, it is not clear how many primers are required in the claims. Claim 1, upon which all other claims depend, recites “HLA gene amplifying primers, comprising primers in any one or more of the following nine primer sets.” It is not clear if this means a primer set is required (e.g. SEQ ID NOS: 1 and 2), or just any primers (e.g. SEQ ID NOS: 1 and 7). Moreover, “comprising . . . in any one or more of the following” is not recognized Markush or SuperGuide language. See MPEP § 2117; SuperGuide Corp. v. DirecTV Enters., Inc., 358 F.3d 870 (Fed. Cir. 2004). The same rationale applies to claims 2-3.
In claims 3-4, it is not clear how a molar ratio is possible among primers themselves. This is not a composition; rather, a mere collection of primers.
Claim 8 is confusing because it recites, in a kit/product, “based on a 3.5 μL system, the adaptor ligation reaction reagent is a mixture of the following reaction reagents.” First, it is not clear what is this “3.5 μL system” because it is entirely generic. Second, it is not clear how this intended use affects the contents of the kit, or if what follows (specific amounts of reagents) are required in the kit, or in use.
In claim 10, the use of “~” is confusing because this means about or approximately, which is not defined.
In claim 13, Applicants use the trademark “PacBio[tm]” which fails to identify the structure, composition, etc. of anything, rather only a source. See MPEP § 2173.05(u).
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. § 102 that form the basis for the rejections under this section made in this Office action:
(A) A person shall be entitled to a patent unless –
(1)the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention; or
(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-3, 5-7 and 9-13 are rejected under 35 U.S.C. § 102(a)(1) as being anticipated by WO2014065410.
As to claim 1, WO2014065410 teaches primers SEQ ID NOS: 3-4 and 9 (R= G or A) in SEQ ID NOS: 1, 11 and 12:
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As to claim 3, WO2014065410 teaches a molar ratio of the primers in each primer set is as follows:
the molar ratio of SEQ ID NO: 1 to SEQ ID NO: 2 is 1:(0.9˜1.1);
the molar ratio of SEQ ID NO: 3 to SEQ ID NO: 4 is 1:(0.9˜1.1);
the molar ratio of SEQ ID NO: 5 to SEQ ID NO: 6 is 1:(0.9˜1.1);
the molar ratio of SEQ ID NO: 7 to SEQ ID NO: 8 is 1:(0.9˜1.1);
the molar ratio of SEQ ID NO: 9 to SEQ ID NO: 10 is 1:(0.9˜1.1);
the molar ratio of SEQ ID NO: 11 to SEQ ID NO: 12 is 1:(0.9˜1.1);
the molar ratio of SEQ ID NO: 12 to SEQ ID NO: 13 is 1:(0.9˜1.1);
the molar ratio of SEQ ID NO: 14 to SEQ ID NO: 15 is 1:(0.9˜1.1);
the molar ratio of SEQ ID NO: 16 to SEQ ID NO: 17 is 18: (1.9˜2.1):(0.9˜1.1): (0.9˜1.1) (Example 1).
As to claim 5, WO2014065410 teaches kit for HLA gene sequencing, comprising HLA gene amplifying primers of claim 1 (Abstract).
As to claim 6, WO2014065410 teaches kit comprising any one or more of a PCR amplification reagent, a sequencing library construction reagent, and a gene purification reagent (Abstract).
As to claim 7, WO2014065410 teaches sequencing library construction reagent comprises any one or more of an adaptor, an adaptor ligation reaction reagent, and an exonuclease (“For example, a DNA library is prepared using a Nextera ™ DNA sample preparation kit manufactured by Illumina and sequenced using a genome sequencer MiSeq system (Illumina).
In this method, since DNA fragmentation and adapter binding via transposome are simultaneously performed, the library can be prepared in a short time of about 90 minutes or less. Paired end analysis is preferably used for sequencing the resulting sample.”).
As to claim 9, WO2014065410 teaches a method of constructing an HLA gene sequencing library, comprising the steps of:
subjecting a test sample to amplification using HLA gene amplifying primers of claim 1 to obtain an amplification product;
performing a ligation reaction between the amplification product and an adaptor to construct a library; and
purifying the library (id.)
As to claim 10, WO2014065410 teaches reaction conditions for the amplification are as follows:
2 min to 3 min holding at 93° C.˜95° C.;
30 cycles, each cycle including 10 seconds at 98° C.; 11 min to 13 min at 68° C. in each cycle from cycle 1 to cycle 10, with addition of 30 seconds per cycle starting from cycle 11; and
10 min holding at 68° C (Example 1).
As to claim 11, WO2014065410 teaches reaction conditions for the ligation reaction are as follows: 20 min to 30 min holding at 37° C.; 20 min to 30 min holding at 16° C. to 25° C.; and 10 min holding at 65° C (Example 1).
As to claim 12, WO2014065410 teaches constructing an HLA gene sequencing library using a method of claim 9, and then sequencing the library (“For example, a DNA library is prepared using a Nextera ™ DNA sample preparation kit manufactured by Illumina and sequenced using a genome sequencer MiSeq system (Illumina).
In this method, since DNA fragmentation and adapter binding via transposome are simultaneously performed, the library can be prepared in a short time of about 90 minutes or less. Paired end analysis is preferably used for sequencing the resulting sample.”).
As to claim 13, WO2014065410 teaches the sequencing is performed based on a PacBio sequencing platform (“For example, a DNA library is prepared using a Nextera ™ DNA sample preparation kit manufactured by Illumina and sequenced using a genome sequencer MiSeq system (Illumina).
In this method, since DNA fragmentation and adapter binding via transposome are simultaneously performed, the library can be prepared in a short time of about 90 minutes or less. Paired end analysis is preferably used for sequencing the resulting sample.”).
Claims 1, 3, and 5-6 are rejected under 35 U.S.C. § 102(a)(1) as being anticipated by WO2018147438.
As to claim 1, WO2018147438 teaches primers SEQ ID NOS: 9-10 in SEQ ID NOS: 17 and 18:
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As to claim 3, WO2018147438 teaches a molar ratio of the primers in each primer set is as follows:
the molar ratio of SEQ ID NO: 1 to SEQ ID NO: 2 is 1:(0.9˜1.1);
the molar ratio of SEQ ID NO: 3 to SEQ ID NO: 4 is 1:(0.9˜1.1);
the molar ratio of SEQ ID NO: 5 to SEQ ID NO: 6 is 1:(0.9˜1.1);
the molar ratio of SEQ ID NO: 7 to SEQ ID NO: 8 is 1:(0.9˜1.1);
the molar ratio of SEQ ID NO: 9 to SEQ ID NO: 10 is 1:(0.9˜1.1);
the molar ratio of SEQ ID NO: 11 to SEQ ID NO: 12 is 1:(0.9˜1.1);
the molar ratio of SEQ ID NO: 12 to SEQ ID NO: 13 is 1:(0.9˜1.1);
the molar ratio of SEQ ID NO: 14 to SEQ ID NO: 15 is 1:(0.9˜1.1);
the molar ratio of SEQ ID NO: 16 to SEQ ID NO: 17 is 18: (1.9˜2.1):(0.9˜1.1): (0.9˜1.1) (Examples ).
As to claim 5, WO2018147438 teaches kit for HLA gene sequencing, comprising HLA gene amplifying primers of claim 1 (Abstract; claims).
As to claim 6, WO2018147438 teaches kit comprising any one or more of a PCR amplification reagent, a sequencing library construction reagent, and a gene purification reagent (Abstract; claims; examples).
Claim Rejection - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 7-13 is rejected under 35 U.S.C. § 103 as being unpatentable over WO2014065410 or WO2018147438, in view of US 20200393472 and MAYOR, N.P. et al. "HLA Typing for the Next Generation." PLOS ONE., Vol. 10, No. 5, 27 May 2015 (2015-05-27), article no. e0127153, and pages 1-12.
This rejection is presented in the interest of compact prosecution to the extent the claims attempt to recite SMRTbell™ sequencing technique applied to the HLA typing of the prior art
It would have been prima facie obvious to a person of ordinary skill in the HLA typing art to apply familiar SMRTbell™ sequencing technique to HLA typing with a reasonable expectation of success.
Neither WO2014065410 or WO2018147438 explicitly teach SMRTbell™ sequencing technique and its amplification and ligation protocols.
However, this technique was routinely applied to HLA typing. For example, US 20140329282 teaches to use SMRTbell™ sequencing technique for familiar HLA typing (paras. 0002, 0113, 0357, 0361, 0368); and temperature and time optimization for amplification and ligation (paras. 0222, 0342ff, Examples). As does US 20200123532 (paras. 0037, 0068, 0170-71, 0198). As does MAYOR, N.P. et al. "HLA Typing for the Next Generation." PLOS ONE., Vol. 10, No. 5, 27 May 2015 (2015-05-27), article no. e0127153, and pages 1-12.
In sum, a skilled artisan would have been motivated to apply familiar SMRTbell™ sequencing technique to familiar HLA typing to achieve familiar results.
Prior Art
The following prior art teaches primers claimed here: WO2021191634; WO2017135396.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MELODY TSUI whose telephone number is (571)272-1846. The examiner can normally be reached Monday - Friday, 9am - 5pm.
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/YUNG-SHENG M TSUI/ Primary Examiner, Art Unit 1684
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