DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Continued Examination Under 37 CFR 1.114
2. A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on has been entered.
3. Applicant's arguments and amendments to the claims presented in the reply of 12 March 2026 have been fully considered but do not place the application in condition for allowance. All rejections and objections not reiterated herein are hereby withdrawn.
Claim Status
4. Claims 1-3, 9, 13-14, 18, 28- 29, 34-36, and 40-42 are pending.
In the reply of 02 August 2023, Applicant elected the species of the the combination of each of loci of BAT25, BAT26, BAT40, ABI-20A and ABI-20B and the combination of the primers of SEQ ID NO: 1-6 and 15-18.
Although claim 1 is not yet allowable, the non-elected species of the one or more of the microsatellite loci of a CAT25 locus, a NR21 locus, a NR22 locus, a NR24 locus, a NR27 locus, an ABI-19 locus, an ABI-17 locus, or an ABI-16 locus in combination with the elected combination of the microsatellite loci of each of BAT25, BAT26, BAT40, ABI-20A and ABI-20B has been rejoined with the elected species.
Claims 1-3, 9, 13-14, 18, 28- 29, 34-36, and 40-42 have been examined herein.
New Claim Rejections - 35 USC § 112(b) – Indefinite
5. 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 40-42 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.
Claims 40-42 are indefinite over the recitation of “an ABI-19 locus, an ABI-17 locus, or an ABI-16 locus.” ThermoFisher (“TrueMark MSI Assay, Easier, more comprehensive MSI testing” 17 October 2019, 4 pages; cited in the IDS) states in Table 1 that these are “MSI markers proprietary to Applied Biosystems.” The specification does not provide a limiting definition for what constitutes “ABI-16,” “ABI-17” and “ABI-19” and there is no well-accepted meaning for these MSI markers in the prior art. The specification exemplifies methods for amplifying ABI-16 using the primer pair of SEQ ID NO: 9 and 10; for amplifying ABI-17 using the primer pair of SEQ ID NO: 11 and 12; and for amplifying ABI-19 using the primer pair of SEQ ID NO: 13 and 14 in an ABI-MSI Assay as set forth in Table 1 of the specification. However, the specification does not indicate that “ABI-16,” “ABI-17” and “ABI-19” are defined by the information provided in Table 1. While Table 1 provides chromosome positions for the microsatellite markers, with respect to reference genome hg38, and provides the length of the amplification product obtained using the stated primers in the ABI-MSI assay, the claims are not limited to methods that perform the ABI-MSI Assay, using the conditions set forth in the specification, and using a primer pair consisting of SEQ ID NO: 9 and 10; a primer pair consisting of SEQ ID NO: 11 and 12; and a primer pair consisting of SEQ ID NO: 13 and 14. The specification does not indicate what constitutes the repeated sequence at the microsatellite loci and whether the primers disclosed in Table 1 amplify only the sequences listed for chromosome 12 and 1, or if the primers cross-hybridize to other sequences in the genome and can amplify other sequences under unspecified amplification conditions. While dependent claims 41 and 42 recite that the microsatellite loci are amplified using one or more of the primers of SEQ ID NO: 7-14 and 19-26, this recitation is not sufficient to define the structure of the “ABI-16,” “ABI-17” and “ABI-19”” loci since claims 41 and 42 do not necessarily require the primers used to amplify “ABI-16,” “ABI-17” and “ABI-19” (i.e., the claims include the primers used only for one or more of the recited CAT25, NR-21, NRE-22, NR-24 and NR-27 loci. Also, claim 41 encompasses methods in which only one of the primers in the primer pair is defined and this is not sufficient to define the “ABI-16,” “ABI-17” and “ABI-19” loci. Accordingly, the metes and bounds of what is encompassed by “ABI-16,” “ABI-17” and “ABI-19” are not clear.
New Claim Rejections - 35 USC § 112(a) – Enablement
6. The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 40-42 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
The following factors have been considered in formulating this rejection (In re Wands, 858F.2d 731, 8 USPQ2d 1400 (Fed. Cir. 1988): the breadth of the claims, the nature of the invention, the state of the prior art, the relative skill of those in the art, the predictability or unpredictability of the art, the amount of direction or guidance presented, the presence or absence of working examples of the invention and the quantity of experimentation necessary.
Herein, claims 40-42 are drawn to methods that further require amplifying an “ABI-16,” “ABI-17” or “ABI-19,” determining the length of the amplified fragments, and comparing the size of the fragments from each locus to that of amplified fragments in a control, wherein a difference in the size between one or more of the amplified fragments between the sample and the control indicates the presence of MSI in the sample.
However, the specification does not adequately disclose what constitutes an “ABI-16,” “ABI-17” and “ABI-19” microsatellite loci.
It is noted that ThermoFisher (“TrueMark MSI Assay, Easier, more comprehensive MSI testing” 17 October 2019, 4 pages; cited in the IDS) states in Table 1 that these are “MSI markers proprietary to Applied Biosystems.”
The specification does not provide a limiting definition for what constitutes “ABI-16,” “ABI-17” and “ABI-19” and there is no well-accepted meaning for these MSI markers in the prior art.
The specification exemplifies methods for amplifying ABI-16 using the primer pair of SEQ ID NO: 9 and 10; for amplifying ABI-17 using the primer pair of SEQ ID NO: 11 and 12; and for amplifying ABI-19 using the primer pair of SEQ ID NO: 13 and 14 in an ABI-MSI Assay as set forth in Table 1. However, the specification does not indicate that “ABI-16,” “ABI-17” and “ABI-19” are defined by the information provided in Table 1. While Table 1 provides chromosome positions for the microsatellite markers, with respect to reference genome hg38, and provides the length of the amplification product obtained using the stated primers in the ABI-MSI assay, the claims are not limited to methods that perform the ABI-MSI Assay, using the conditions set forth in the specification, and using a primer pair consisting of SEQ ID NO: 19 and 10 to amplify ABI-16, a primer pair consisting of SEQ ID NO: 11 and 12 to amplify ABI-17, or a primer pair consisting of SEQ ID NO: 13 and 14 to amplify ABI-19. The specification does not indicate what constitutes the repeated sequence at the microsatellite loci – i.e., if it is a mono repeat or dinucleotide repeat etc. and what particular nucleotide(s) are repeated. It is also unclear as to the relationship between the “Genome Position hg18” and the “Amp Length” because the “Amp Length” is shorter than the region encompassed by the “Genome Position hg18.” For example, for “ABI-16,” the listed genome positions encompass a 319bp region, but the “Amp Length” is 115 (bp), using primers of 20 and 18 nucleotides in length.
There is also no information provided as to whether the primers disclosed in Table 1 amplify only the sequences listed for chromosome 17 and 1, or if the primers cross-hybridize to other sequences in the genome and can amplify other sequences under unspecified amplification conditions. Note that the present claims do not require any particular conditions under which amplification is performed.
While dependent claims 41 and 42 recite that the microsatellite loci are amplified using one or more of the primers of SEQ ID NO: 7-14 and 19-26, this recitation is not sufficient to define the structure of the “ABI-16,” “ABI-17” and “ABI-19”” loci since claims 41 and 42 do not necessarily require the primers used to amplify “ABI-16,” “ABI-17” and “ABI-19” (i.e., the claims include the primers used to amplify one or more of the additionally recited CAT25, NR-21, NRE-22, NR-24 and NR-27 loci). Also, claim 41 encompasses methods in which only one of the primers in the primer pair is defined and this is not sufficient to define the “ABI-16,” “ABI-17” and “ABI-19” loci. However, the specification does not exemplify methods which use only 1 primer to amplify the recited microsatellite loci. It is unclear as to what would be the identity of the sequences amplified, particularly under any amplification conditions, and what would be the identity of a microsatellite repeat within the amplified region.
Without a clear and limiting definition in the specification for what constitutes the microsatellite loci “ABI-16,” “ABI-17” and “ABI-19,” the artisan cannot practice the claimed methods without undue experimentation.
Case law has established that “(t)o be enabling, the specification of a patent must teach those skilled in the art how to make and use the full scope of the claimed invention without ‘undue experimentation.” In re Wright 990 F.2d 1557, 1561. In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970) it was determined that “(t)he scope of the claims must bear a reasonable correlation to the scope of enablement provided by the specification to persons of ordinary skill in the art.” The amount of guidance needed to enable the invention is related to the amount of knowledge in the art as well as the predictability in the art. Further, the Court in Genetech Inc. v Novo Nordisk 42 USPQ2d 1001 held that “(I)t is the specification, not the knowledge of one skilled in the art that must supply the novel aspects of the invention in order to constitute adequate enablement."
Additionally, as set forth in Rasmusson v. SmithKline Beecham Co., 75 USPQ2d 1297, 1302 (CAFC 2005), enablement cannot be established unless one skilled in the art "would accept without question" an Applicant's statements regarding an invention, particularly in the absence of evidence regarding the effect of a claimed invention.
Specifically:
"As we have explained, we have required a greater measure of proof, and for good reason. If mere plausibility were the test for enablement under section 112, applicants could obtain patent rights to "inventions consisting of little more than respectable guesses as to the likelihood of their success. When one of the guesses later proved true, the "inventor" would be rewarded the spoils instead of the party who demonstrated that the method actually worked. That scenario is not consistent with the statutory requirement that the inventor enable an invention rather than merely proposing an unproved hypothesis."
Herein, although the level of skill in the art is high, given the lack of disclosure in the specification and in the prior art and the unpredictability of the art, it would require undue experimentation for one of skill in the art to make and use the invention as broadly claimed.
Maintained / Modified Claim Rejections - 35 USC § 112(a) - New Matter
7. Claims 1-3, 9, 13-14, 18, 28- 29, 34-36, and 40-42 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a New Matter rejection.
The disclosure as originally filed does not provide basis for the amendment to the claim 1 to recite “wherein the BAT25 locus is l co-amplified with primers having at least 90% identity to SEQ ID NOS. 1-2, the BAT26 locus is co-amplified with primers having at least 90% identity to SEQ ID NOS. 3-4, the BAT40 locus is co-amplified with primers having at least 90% identity to SEQ ID NOS. 5-6, the ABI-20A locus is co-amplified with primers having at least 90% identity to SEQ ID NOS. 15-16, and the ABI-20B locus is co-amplified with primers having at least 90% identity to SEQ ID NOS.17-18.”
In the remarks filed on 12 March 2026, Applicant states that support for the amendments to the claims is found in the claims and specification as filed, “e.g. at Table 1.”
However, the originally filed claims and the originally filed disclosure do not disclose primers having “at least 90% identity” to SEQ ID NOS. 1-6 and 15-18” and particularly do not disclose amplifying the ABI-20A locus and/or ABI-20B locus using a primer pair having “at least 90% identity” to SEQ ID NOS.15-16 and SEQ ID NO: 17-18, respectively or amplifying the BAT-25, Bat26 AND BAT40 loci with the primer pairs having “at least 90% identity” to SEQ ID NO: 1 and 2, SEQ ID NO: 3 and 4, and SEQ ID NO: 5 and 6, respectively. Rather, the originally filed claims and originally filed disclosure teach only amplifying the ABI-20A locus and ABI-20B using the primers of SEQ ID NO: 15-18. See for example claim 20, filed with the application on 06 November 2020:
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Further, Table 1 of the specification discloses only the particular primer pairs of SEQ ID NO: 1 and 2, SEQ ID NO: 3 and 4, SEQ ID NO: 5 and 6, SEQ ID NO: 15 and 16 and SEQ ID NO: 17 and 18. Table 1 does not provide basis for the concept of primers that have “at least 90%” and thereby 90% or 91% …up to less than 100% identity with SEQ ID NO: 1-6 and 15-18.
If Applicant maintains that the originally filed disclosure provides basis for the amended claims, Applicant should point to specific teachings (e.g., by paragraph number) in the present application to establish basis for each of the recitations set forth in the claims.
See MPEP 2163 II at “(b) New Claims, Amended Claims, or Claims Asserting Entitlement to the Benefit of an Earlier Priority Date or Filing Date under 35 U.S.C. 119, 120, 365, or 386” which states:
“To comply with the written description requirement of 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph, or to be entitled to an earlier priority date or filing date under 35 U.S.C. 119, 120, 365, or 386, each claim limitation must be expressly, implicitly, or inherently supported in the originally filed disclosure.”
Response to Remarks:
In the reply of 12 March 2026, Applicant states:
“The Examiner asserts that, because the claims recite at least 90% identity to only a single primer for each of the ABI-20A and ABI-20B loci-and not to a corresponding second primer-the claims fail to define the complete structure or the metes and bounds of the ABI-20A and ABI-20B loci.
As amended, claim 1 now recites two primers, each having at least 90% identity to specified primer sequences, for amplifying each of the ABI-20A and ABI-20B loci, and further recites primer pairs for the other claimed loci. A person of ordinary skill in the art, using the primer pairs recited in amended claim 1, would be able to generate amplified fragments comprising nucleic acid sequences from each locus as claimed, thereby enabling practice of the invention and supplying definite claim boundaries..”
However, the basis for the written description / new matter rejection is that the disclosure as originally filed does not provide basis for the amendment to the claims to recite that the primers have “at least 90% identity” to SEQ ID NO: 1-6 and 15-18. The originally filed disclosure provides support only for primers consisting of the specific nucleotide sequences of SEQ ID NO :1-6 and 15-18. The response does not point to where the originally filed disclosure teaches primers that have only 90% to less than 100% identity with SEQ ID NO: 1-6 and 15-18 and which amplify the recited microsatellite loci.
Further, it is not a question of whether the subject matter added to the claims would have been obvious based on the teachings in the prior art, but whether the specification as originally filed provided support for the amended claims. See MPEP 2163IB:
“The proscription against the introduction of new matter in a patent application (35 U.S.C. 132 and 251) serves to prevent an applicant from adding information that goes beyond the subject matter originally filed…Thus, the written description requirement prevents an applicant from claiming subject matter that was not adequately described in the specification as filed. New or amended claims which introduce elements or limitations that are not supported by the as-filed disclosure violate the written description requirement.”
MPEP 2163 II3(b) goes on to state:
“To comply with the written description requirement of 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph, or to be entitled to an earlier priority date or filing date under 35 U.S.C. 119, 120, 365, or 386, each claim limitation must be expressly, implicitly, or inherently supported in the originally filed disclosure. When an explicit limitation in a claim "is not present in the written description whose benefit is sought it must be shown that a person of ordinary skill would have understood, at the time the patent application was filed, that the description requires that limitation." Hyatt v. Boone, 146 F.3d 1348, 1353, 47 USPQ2d 1128, 1131 (Fed. Cir. 1998)… If the originally filed disclosure does not provide support for each claim limitation, or if an element which applicant describes as essential or critical is not claimed, a new or amended claim must be rejected under 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph, as lacking adequate written description…”
See also Lockwood v. American Airlines Inc., 41 USPQ2d 1961 (Fed. Cir. 1977), “Entitlement to a filing date does not extend to subject matter which is not disclosed, but would be obvious over what is expressly disclosed. It extends only to that which is disclosed. It extends only to that which is disclosed.”
The rejection is maintained for the reasons set forth above.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CARLA J MYERS whose telephone number is (571)272-0747. The examiner can normally be reached M-Th 6:30-5:00 EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Wu-Cheng (Winston) Shen can be reached on 571-272-0731. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/CARLA J MYERS/Primary Examiner, Art Unit 1682
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