DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
This application is a divisional of US application no. 16/103,516, filed 08/14/2018 (now US Patent No. 11,746,379), which is a divisional of US application no. 14/672,066, filed 03/27/2015 (now US Patent No. 10,072,298), claiming priority to US provisional applications 61/971,455, 61/993,732, 62/004,727, and 62/092,898; US application 16/672,066 is also a continuation in part of US application 14/214,300 (now abandoned), claiming priority to US provisional applications 61/813,182, 61/813,465, 61/824,253, 61/860,115, 61/907,939, 61/915,392, 61/935,650, and 61/940,226. It is noted that the elected species was first disclosed in provisional application 61/860,115, filed 07/30/2013.
Election/Restrictions
Applicant’s election of the species of SEQ ID NO: 72, breast carcinoma, and the gene fusion partner genes of RAR and HOXB3 in the reply filed on 10 December 2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)). Applicant has identified claims 1-2 and 4-20 as reading on the elected species.
Claim 3 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 10 December 2025.
Claim Rejection – Improper Markush Grouping
Claims 1-2 and 4-20 are rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
Initially, it is noted that each of independent claims 1 and 8 recite methods embracing any of SEQ ID NO: 1-328; independent claim 14 is also included in this rejection as it encompasses embodiments as set forth in dependent claims 15-19 (with claim 15 reciting methods comprising amplifying a nucleic acid comprising a sequence selected from SEQ ID NOS 1-328).
The Markush grouping of SEQ ID NOS: 1-328 is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons: each of the alternative sequences is characterized by a distinct/different nucleotide sequence/structure and associated functional characteristics (including associations with different types of cancer). The elected sequence of SEQ ID NO: 72 – which is disclosed in the specification as being a fusion of the RARA and HOXB3 genes associated with invasive breast carcinoma – is the only sequence disclosed in the specification as having such a structure and associated function (and is thus also not disclosed in the specification as being functionally equivalent and having a common use with other members of the recited group, nor was this known in the prior art). Therefore, methods requiring amplification/ detection of SEQ ID NO: 72 do not form a proper Markush grouping with methods requiring amplification of the other alternative sequences set forth in the claims.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
Claim Rejections - 35 USC § 112(b)/second paragraph
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-2 and 4-20 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Rejections applying to claim 1 and claims dependent therefrom:
Claims 1-2 and 4-7 are indefinite because: a) claim 1 recites detecting one of a group of cancer types “in a sample”, but does not reference use of a sample in the active steps of the claim (i.e., the “amplifying” and “detecting” of the claim refer to a nucleic acid, but nothing in the claim clearly connects that “nucleic acid” to the sample); and b) claim 1 concludes with the statement “wherein detecting the nucleic acid…indicates that….present in the sample”, which is confusing/unclear language (as some element of this phrase appears to be missing). While some persons of skill in the art might assume that the recited “nucleic acid” employed in the “amplifying” originates in/from the “sample”, given the lack of any actual recitation of use of the sample or materials therefrom, other such artisans could reasonably interpret the claim as embracing something broader/different. Accordingly, further clarification is required.
Claims 2 and 4 are indefinite over the recitation in claim 2 of the limitation “wherein a gene fusion from Table_____ is detected”. The requirement for a “gene fusion from” a Table/Tables renders the claims indefinite because it is unclear what elements of the Table(s) are/are not actually required to meet the claims. It is noted that MPEP 2173.05(s) states:
Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table "is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience." Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993) (citations omitted).
In the instant case, what is claimed may be defined by words (or a sequence identifier), and the reference to a Table simply creates confusion regarding what is/isn’t claimed.
Additionally, while claim 1 is unclear as noted above, that claim appears to require amplifying and detecting a specific sequence that corresponds to a fusion, and it thus also not clear how the reference to a “gene fusion from” a Table might further limit what is claimed. Clarification is therefore needed.
Claim 4 is indefinite over the recitation of the limitation “wherein a gene fusion partner is two genes chosen from…”, because it is unclear how this further limits what is claimed. While claim 2 references a “gene fusion” (in an unclear manner, as noted above), there is no prior use of the term “gene fusion partner”, and as claim 1 is directed to amplifying/detecting a recited SEQ ID NO, it is not clear how claim 4 relates to claims 1 and 2. This claim appears to potentially refer to some different/further claim element that may be required, but which is not previously mentioned. Accordingly, further clarification regarding how claim 4 relates to and further limits the claims from which it depends is needed.
Claim 7 is indefinite over the recitation of the limitation “further comprising administering to a patient with a gene fusion a drug, wherein the gene fusion is disclosed in Table ____”. First, the reliance on a Table or Tables to define what is claimed renders the claim indefinite for the same reasons given above regarding claim 2, i.e., it is unclear what elements of the Table(s) are/are not actually required to meet the claims, and the reliance on a Table/Tables creates confusion regarding the boundaries of the claim. Second, in addition to the lack of clarity regarding what type of “gene fusion” is encompassed by the claim, the language “administering to a patient with a gene fusion a drug” is unclear because it is unclear whether “a patient” does or does not refer to the previously specified patient (e.g., from whom the “patient sample” originated, or as “diagnosed” in claim 6, etc.); some persons of skill in the art would reasonably interpret the limitation “a patient” as referring to a previously mentioned patient (and potentially a patient in whom some type of fusion structure was amplified/detected), whereas others would reasonably interpret the use of “a patient” rather than “the patient” as a possible reference to any type of patient (having any “gene fusion” disclosed in a Table as recited in the claim, etc.). Accordingly, clarification is needed regarding the meaning and boundaries of claim 7.
Rejections applying to claim 8 and claims dependent therefrom:
Claims 8-13 and 20 are indefinite over the recitation in independent claim 8 of the limitation “the method comprising use of a set of probes for…”, because it is unclear whether the limitations following “use of a set of probes for” are setting forth required active steps (such that the claims are drawn to a method requiring “amplifying” and “detecting” as recited in claim 8), or simply properties of/an intended use for the “set of probes” (i.e., such that the claims embrace any “use of a set of probes” having the recited properties). As these different reasonable interpretations of the claim language impart different boundaries on what is claimed, further clarification is required. Additionally:
a) to the extent that the claims are directed to the former embodiment (i.e., a method requiring performance of the recited “amplifying” and “detecting”), it is unclear how and whether these activities relate to/require a detecting actually involving the referenced “sample”, given that the active steps of the claims never recite use of a sample, materials from a sample, etc. (but rather simply refer to amplifying “a nucleic acid” of unspecified origin); and
b) to the extent that the claims are directed to the latter embodiment (i.e., any “use of a set of probes” having the recited characteristics/intended use), the claims are also indefinite for attempting to claim a process without setting forth any steps, as the claim fails to indicate how the recited “use” is practiced (see MPEP 2173.05(q) regarding “Use” Claims, and see also the related rejection under 35 USC 101 below).
Claims 8-13 and 20 are also indefinite over the recitation in independent claim 8 of the limitation “wherein detecting the nucleic acid comprising ____ indicates that a cancer is present in the sample” because (to the extent that the claim is directed to method in which “amplifying” and “detecting” are performed) the claim as written does not clearly require any active/manipulative steps in which a sample or materials therefrom is employed. Thus, it is not clear how the activities set forth in the claim relate to actually indicating cancer presence in a/the sample, and further clarification is needed.
Claims 9-11 are also indefinite over the recitation in claim 9 “wherein detecting the nucleic acid…indicates that….is present in the sample”, because (as discussed above with regard to analogous language in independent claim 8) the claims as written do not actually require use of nucleic acids originating from a sample/the sample set forth in the claims. Thus, it is not clear how the activities set forth in the claim relate to actually indicating cancer presence in a/the sample, and further clarification is needed.
Claims 10-11 are indefinite over the recitation in claim 10 of the limitation “wherein a gene fusion from Table_____ and/or a gene variant from Table ____ is detected”. The requirement for a “gene fusion from” and/or a “gene variant from” a Table/Tables renders the claims indefinite because it is unclear what elements of the Table(s) are/are not actually required to meet the claims. It is again noted that MPEP 2173.05(s) states:
Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table "is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience." Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993) (citations omitted).
In the instant case, what is claimed may be defined by words (or a sequence identifier), and the reference to Tables simply creates confusion regarding what is/isn’t claimed.
Additionally, while claim 8 is unclear as noted above, that claim appears to (at least in some possible embodiments) require amplifying and detecting a specific sequence that corresponds to a fusion, and it thus also not clear how the reference to a “gene fusion from” (or “gene variant from”) a Table might further limit what is claimed (to the extent that the claim is directed to such an embodiment). Clarification is therefore needed.
Claim 11 is indefinite over the recitation of the limitation “wherein a gene fusion partner is two genes chosen from…”, because it is unclear how this further limits what is claimed. While claim 10 recites a “gene fusion” as an alternative, there is no prior use of the term “gene fusion partner”, and this claim appears to refer to some different/ further claim element that may be required, but which is not previously mentioned. Accordingly, further clarification is needed regarding how claim 11 relates to and further limits the claims from which it depends is needed.
Claim 13 is indefinite over the recitation of the limitation “further comprising treating the patient comprising administering to a patient with a gene fusion and/or a gene variant a drug, wherein the gene fusion from Table ____ and/or the gene variant from Table ___ is detected”. First, the reliance on a Table or Tables to define what is claimed renders the claim indefinite for the same reasons given above regarding, e.g., claims 10-11, i.e., it is unclear what elements of the Table(s) are/are not actually required to meet the claims, and the reliance on a Table/Tables creates confusion regarding the boundaries of the claim. Second, in addition to the lack of clarity regarding what type of “gene fusion”/”gene variant” is encompassed by the claim, the limitations “the gene fusion from Table __” and “the gene variant from Table __” lack clear antecedent basis (as such a type of gene fusion/gene variant has not been previously referenced). Third, the language “treating the patient comprising administering to a patient with a gene fusion and/or a gene variant a drug” is unclear because: a) the reference to “the patient” followed by “a patient” is confusing with regard to what “patient” is being indicated; and b) it is unclear whether “a patient” does or does not refer to the previously specified patient (e.g., from whom the “patient sample” originated, or as “diagnosed” in claim 12, etc.); some persons of skill in the art would reasonably interpret the limitation “a patient” as referring to a previously mentioned patient (and potentially a patient in whom some type of fusion structure was amplified/detected), whereas others would reasonably interpret the use of “a patient” rather than “the patient” as a possible reference to any type of patient (having any “gene fusion”/”gene variant” disclosed in a Table as recited in the claim, etc.). Accordingly, clarification is needed regarding the meaning and boundaries of claim 13.
Claim 20 (dependent from claim 8) is also indefinite for the reasons noted immediately above regarding analogous language in claim 13 pertaining to the reliance on Tables in the claim and the lack of clarity regarding what type of “gene fusion”/”gene variant” is encompassed by the claim, and is further indefinite because the limitation “the patient” lacks antecedent basis (as claim 8 never refers to a patient), such that it is entirely unclear how “treating the patient comprising administering to a patient” might be performed. Further clarification is required.
Rejections applying to claim 14 and claims dependent therefrom:
Claims 14-19 are indefinite over the recitation in independent claim 14 of the limitation “the method comprising use of a set of probes for…”, because it is unclear whether the limitations following “use of a set of probes for” are setting forth required active steps (such that the claims are drawn to a method requiring “amplifying” and “detecting” as recited in claim 14), or simply properties of/an intended use for the “set of probes” (i.e., such that the claims embrace any “use of a set of probes” having the recited properties). As these different reasonable interpretations of the claim language impart different boundaries on what is claimed, further clarification is required. Additionally:
a) to the extent that the claims are directed to the former embodiment (i.e., a method requiring performance of the recited “amplifying” and “detecting”), it is unclear how and whether these activities relate to/require a detecting actually involving the referenced “sample”, given that the active steps of the claims never recite use of a sample, materials from a sample, etc. (but rather simply refer to amplifying “a nucleic acid” of unspecified origin); and
b) to the extent that the claims are directed to the latter embodiment (i.e., any “use of a set of probes” having the recited characteristics/intended use), the claims are also indefinite for attempting to claim a process without setting forth any steps, as the claim fails to indicate how the recited “use” is practiced (see MPEP 2173.05(q) regarding “Use” Claims, and see also the related rejection under 35 USC 101 below).
Claims 14-19 are indefinite over the recitation in independent claim 14 of the limitation “wherein the set of probes specifically recognizes a fusion between the RARA gene and the HOXB3 gene”, because it is unclear how this further limits the set of probes of the claims. More particularly, the term “specifically recognizes” is not defined in the specification and does not have any standard meaning in the art, such that it is not clear what relationship between the “set of probes” and the fusion is required to meet the requirements of the claims. Further, this claim language is unclear with regard to whether the “set” requires multiple probes related “specifically” to target sequences including portions of both gene (i.e., overlapping the junction of the two genes), or whether, e.g., a set of probes including at least one probes targeting each gene (in some “specific” manner) would be embraced by the claims. Accordingly, the boundaries of what is claimed are not clear.
Claims 14-19 are also indefinite over the recitation in independent claim 14 of the limitation “wherein detecting the nucleic acid comprising SEQ ID NO: 272, indicates that breast carcinoma is present…” because: a) there is insufficient antecedent basis for the limitation “the nucleic acid comprising SEQ ID NO: 272”; and b) it is unclear how this limitation relates to the rest of the claim (which pertains to a either a method requiring, or use of a set of probes for, amplifying/detecting a different target sequence). While the reference to SEQ ID NO: 272 is likely a typographical error, the claim as presently written is indefinite, and clarification is required.
Claim 16 is indefinite over the recitation in the of the limitation “wherein a gene fusion from Table_____ and/or a gene variant from Table ____ is detected”. Again, the requirement for a “gene fusion from” and/or a “gene variant from” a Table/Tables renders the claims indefinite because it is unclear what elements of the Table(s) are/are not actually required to meet the claims. It is again noted that MPEP 2173.05(s) states:
Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table "is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience." Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993) (citations omitted).
In the instant case, what is claimed may be defined by words (or a sequence identifier), and the reference to Tables simply creates confusion regarding what is/isn’t claimed.
Additionally, while claim 14 is unclear as noted above, that claim appears to (at least in some possible embodiments) require amplifying and detecting a specific sequence that corresponds to a fusion, and it thus also not clear how the reference to a “gene fusion from” (or “gene variant from”) a Table might further limit what is claimed (to the extent that the claim is directed to such an embodiment). Clarification is therefore needed.
Claim 17 is indefinite over the recitation of the limitation “wherein a gene fusion partner is two genes chosen from…”, because it is unclear how this further limits what is claimed. While claim 14 recites a “fusion between the RARA gene and the HOXB3”, there is no prior use of the term “gene fusion partner”, and as RARA and HOXB3 are recited in claim 17, this claim appears to refer to some different/further claim element that may be required, but which is not previously mentioned. Accordingly, further clarification is needed regarding how claim 17 relates to and further limits the claims from which it depends is needed.
Claim Rejections - 35 USC § 112(d)/fourth paragraph
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 6-7 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. As noted above, claim 1 (from which claims 6-7 depend) is indefinite with regard to whether the claim does/does not require an amplifying and detecting practiced on nucleic acid from the previously recited sample; this rejection applies to the claim to the extent that it requires a method in which the “amplifying” and “detecting” require use of sample nucleic acid. As this possible embodiment already requires amplifying and detecting the specified sequence, claims 6-7 are not properly further limiting to the extent that they embrace embodiments in which such an amplifying/detecting is not required (as is the case with regard to at least some embodiments of claim 6, given that it includes the conditional/contingent language “diagnosing…when a nucleic acid comprising a sequence….is present in the patient sample”). In other words, if the independent claim requires amplifying/detecting a particular nucleic acid, then a dependent claim that embraces embodiments in which such an amplifying/detecting of that nucleic acid is optional/conditional is broadening, and the dependent claim fails to include all limitations of the independent claim. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claims 12-13 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. As noted above, claim 8 (from which claims 12-13 depend) is indefinite with regard to whether the claim does/does not require an amplifying and detecting practiced on nucleic acid from the previously recited sample; this rejection applies to the claim to the extent that it requires a method in which the “amplifying” and “detecting” require use of sample nucleic acid. As this possible embodiment already requires amplifying and detecting the specified sequence, claims 12-13 are not properly further limiting to the extent that they embrace embodiments in which such an amplifying/detecting is not required (as is the case with regard to at least some embodiments of claim 12, given that it includes the conditional/contingent language “diagnosing…when a nucleic acid comprising a sequence….is present in the patient sample”). ”). In other words, if the independent claim requires amplifying/ detecting a particular nucleic acid, then a dependent claim that embraces embodiments in which such an amplifying/detecting of that nucleic acid is optional/conditional is broadening, and the dependent claim fails to include all limitations of the independent claim. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim 19 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. As noted above, claim 14 (from which claim 19 depends) is indefinite; this rejection applies to the claim to the extent that it requires a method in which the “amplifying” and “detecting” of SEQ ID NO: 72 referenced in the claim are actually performed. As this possible embodiment requires amplifying and detecting the specified sequence, claim 19 is not properly further limiting to the extent that it embraces embodiments in which such an amplifying/detecting is not required (as is the case with regard to at least some embodiments of claim 19, given that it includes the conditional/contingent language “diagnosing…when a nucleic acid comprising a sequence….is present in the patient sample”). ”). In other words, if the independent claim requires amplifying/detecting a particular nucleic acid, then a dependent claim that embraces embodiments in which such an amplifying/detecting of that nucleic acid is optional/conditional is broadening, and the dependent claim fails to include all limitations of the independent claim. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 112(a)/first paragraph – Scope of Enablement
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-2 and 4-20 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for methods in which a nucleic acid comprising SEQ ID NO: 72 is detected as an indicator of the presence of breast carcinoma in a sample, does not reasonably provide enablement for methods in which a nucleic acid comprising SEQ ID NO: 72 is detected as an indicator of any of the other cancer types recited in the claims (see independent claim 1 as well as dependent claims 6, 9, 12, 15, and 19), or (with particular regard to independent claims 8 and 14 and claims dependent therefrom) for methods comprising any “use of a set of probes” having properties as recited in the claims (which is one embodiment that appears to be embraced by the claims) to achieve “detecting a cancer” (claim 8 and claims dependent therefrom) or “detecting breast carcinoma” (claim 14 and claims dependent therefrom). The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
There are many factors to be considered when determining compliance with the enablement requirement of 35 USC 112(a), including, but not limited to: (A) the breadth of the claims; (B) the nature of the invention; (C) the state of the prior art; (D) the level of one of ordinary skill; (E) the level of predictability in the art; (F) the amount of direction provided by the inventor; (G) the existence of working examples; and (H) the quantity of experimentation needed to make or use the invention based on the content of the disclosure. In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988). All evidence related to each of these factors has been considered, and the conclusion that enablement is lacking, as set forth below, is based on the evidence as a whole. (MPEP 2164.01(a)).
Initially, it is reiterated that the elected invention under consideration herein is methods employing/related to SEQ ID NO: 72, the detection of breast carcinoma, and the gene fusion partners RARA and HOXB3 (with SEQ ID NO: 72 being disclosed as a specific example of such a fusion). However, regarding claim 1 and claims dependent thereof, the claims as presently written embrace methods in which SEQ ID NO: 72 is amplified and detected as an indicator of any of a variety of different cancers. Independent claims 8 and 14 and claims dependent therefrom (as discussed above) do not clearly require methods in which SEQ ID NO: 72 is actually amplified and detected, but also appear to embrace methods comprising any “use of a set of probes” that may function in such activities (but without clearly requiring the performance of steps resulting in detection of SEQ ID NO: 72). Further, claim 8 embraces detection of any “cancer”, while claim 14 also encompasses at least some embodiments (as evidenced by its dependent claims 15-19) in which SEQ ID NO: 72 may be used as an indicator of any of a variety of different cancers.
It is unpredictable as to whether one of skill in the art could use Applicant’s invention in a manner commensurate in scope with the present claims. The specification discloses instant SEQ ID NO: 72 as a single example of a RARA/HOXB3 fusion, associated with a single type of cancer (invasive breast carcinoma) (see in particular Table 1 and Table 4). The specification provides no other examples of this nucleic acid, or other similar nucleic acids (e.g., other RARA/HOXB3 fusions) occurring in association with any other cancer, including any of the other preferred cancer types recited in the claims; rather, the specification discloses detecting different gene fusions as indicators of the various other cancer types embraced by the claims (corresponding to different methods recited in the alternative throughout the claims). Additionally, while the disclosure teaches that active steps of amplifying and detecting SEQ ID NO: 72 could be employed in breast carcinoma detection, the specification does not disclose/exemplify other types of “uses” of probes sets capable of functioning in amplification/detection of SEQ ID NO: 72 – with such “uses” not requiring the actual performance of any active/manipulative steps (as appear to also be potentially embraced by the claims) – in achieving detection of breast carcinoma. Lacking guidance from the specification, one of skill in the relevant art may look to the teachings of the prior art for further enabling guidance regarding a claimed invention. However, in the present case, while the prior art does provide another example of a RARA fusion associated with breast cancer - a RARA-PKIA fusion, as exemplified by Edgren et al (Genome Biology 12:R6 [2011]; cited herein), in particular at Table 1 and Figure 2 – the prior art is silent with regard to any other RARA-HOXB3 gene fusions known to be associated with breast cancer or any of the other cancer types of the claims (such that the prior art cannot be relied upon to supply guidance with regard to what is missing from Applicant’s disclosure). Further, neither the specification nor the prior art provide any teachings related to successful use of a “set of probes” as specified in claims 8 and 14 in performing cancer detection without the performance of any active method steps (and particularly without the actual successful detection of SEQ ID NO: 72). Given the high skill level of one skilled in the relevant art, it is clearly within the ability of such an artisan to conduct further experimentation aimed at determining, e.g., whether nucleic acids specified in the claims (in this case SEQ ID NO: 72) occur in association with other cancer types, and at identifying other “uses” of probes sets of the claims that may relate to cancer detection; however, the outcome of such experimentation is unknown and unpredictable. Further, based on the actual teachings of the specification and the most closely related prior art (Edgren et al), one skilled in the relevant art would not have had any expectation that instant SEQ ID NO: 72 would be found in association with other cancer types; thus, there would have been no expectation before Applicant’s effective filing date that any embodiment other than that disclosed in the specification – i.e., the performance of amplification/detection of SEQ ID NO: 72 as an indicator of breast carcinoma – was enabled. Accordingly, given the lack of guidance and direction in the specification and prior art, and the unpredictability of the art, it would have required undue experimentation to use Applicant’s invention in a manner reasonably commensurate with the instant claims. With further regard to those dependent claims reciting lists of gene fusions/variants and referencing gene fusions/variants in Tables (see claims 2, 4, 7, 10-11, 13, 16-17, and 20), it is noted that each of these claims recites (in an unclear manner) a variety of possible different fusion molecules associated with different cancer types, but lacking, e.g., any required specific associations between such different structures and particular cancers (and furthermore the invention under consideration is that corresponding to instant SEQ ID NO: 72; nothing in these dependent claims contributes anything further related to the enablement of the invention under consideration). Dependent claims 6-7, 9, 12-13, and 15-19 embrace a variety of different possible cancers that, based on the present wording of the claims, might be “indicated” by SEQ ID NO: 72 (whereas the guidance provided in the specification discloses SEQ ID NO: 72 as a specific indicator of one particular cancer, breast carcinoma). Accordingly, all of the claims presently under consideration lack enablement for reasons given above.
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 1-2 and 4-20 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural phenomenon/law of nature, and/or an abstract idea, without significantly more.
Initially, it is noted that some claims (claims 8 and 14 and claims dependent therefrom) are also rejected as non-statutory for the reasons given below (see paragraph 16); this rejection applies to those claims to the extent that they may require performing steps such as amplifying and detecting elected SEQ ID NO: 72 as an indicator of cancer/breast carcinoma (which is another embodiment that also appears to be encompassed by these claims).
Regarding claim 1 and claims dependent therefrom (claims 2 and 4-7), independent claim 1 as directed to the elected invention recites “detecting” breast carcinoma, “detecting the presence of” a nucleic acid (specifically SEQ ID NO: 72), and “wherein detecting the nucleic acid indicates that….breast carcinoma…present in the sample [sic]”; the presence of SEQ ID NO: 72 in association with breast cancer is a natural phenomenon/law of nature, and “detecting” as recited in the claims encompasses activities that may be performed entirely in the human mind – e.g., forming a conclusion regarding what is indicated by the result of a nucleic acid amplification, as well as regarding what is indicated with respect to breast cancer based on the presence of a naturally occurring nucleic acid – i.e., abstract ideas. Regarding claims 8-13 and 20, independent claim 8 similar recites “detecting” cancer and a nucleic acid, “wherein detecting…indicates that a cancer is present in” a sample; again, the occurrence of SEQ ID NO: 72 in association with cancer is a natural phenomenon, while such “detecting” embraces thinking about what test results indicate, i.e., abstract ideas. Regarding claims 14-19, independent claim 14 also recites “detecting” of the type specified above and with regard to nucleic acid that occurs naturally in cancer, such that both a natural phenomenon/law of nature and abstract ideas are recited.
This judicial exceptions identified above are not integrated into a practical application because: a) with regard to claim 1 and claims dependent therefrom, the only required active method step of the claim – of “amplifying a nucleic acid” – is a data gathering step that does not add a meaningful limitation to the method as it is insignificant extra-solution activity. Regarding claim 8 and claim 14 and claims dependent therefrom, even to the extent that those claims do require an active step of “amplifying” a nucleic acid, this similarly constitutes a data gathering step (i.e., insignificant extra-solution activity). It is noted that the recited “set of probes” that “specifically recognizes a fusion” of claim 14 is an unclear/indefinite limitation as discussed above, and that the claim as written does not clearly recite/require use of such probes in the “amplifying” and/or “detecting”, such that this limitation does not clearly further limit the actions performed as part of the claimed method. Thus, none of these claims add anything that constitutes a practical application/implementation of a JE. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the activity of amplifying/detecting nucleic acid (which is broadly recited in the present claims) has been recognized by the courts as well-understood, routine, and conventional activity in the life science arts when claimed at a high level of generality (as is the case here); see MPEP 2106.05(d)(II), and particularly Genetic Techs. Ltd. v. Merial LLC, 818 F.3d 1369, 1376, 118 USPQ2d 1541, 1546 (Fed. Cir. 2016); Ariosa Diagnostics, Inc. v. Sequenom, Inc., 788 F.3d 1371, 1377, 115 USPQ2d 1152, 1157 (Fed. Cir. 2015). Additionally, it is reiterated that the set of probes referenced in claim 14 is not clearly indicated as being employed in either the recited “amplifying” and/or “detecting” of the claim. While it is noted that the association between instant SEQ ID NO: 72 and breast carcinoma was not known in the prior art as of Applicant’s effective filing date, this association is itself a natural phenomenon/law of nature, rather than something more than a judicial exception. An inventive concept cannot be furnished by a judicial exception (i.e., a law of nature/natural phenomenon/abstract idea) itself (see MPEP 2106.05(I)). Thus, the requirement to amplify and detect a nucleic acid comprising SEQ ID NO: 72 - even to the extent that the claim may encompass amplification in combination with broadly/generally recited wet/manipulative types of “detecting” – cannot be considered as amounting to something “significantly more” than a JE.
With further regard to dependent claims 2 and 4, these claims reference further gene fusions without clearly adding any further requirements with regard to actions/steps that must be performed (even with regard to the gathering of data/information); thus, the claims do not integrate any JE into a practical application or add anything more than a JE. Claims 5-7 require a “patient sample” but no such sample is necessarily employed in the active steps of claim 1; the “diagnosing” of claims 6-7 is a further type of activity that may be performed in the human mind (i.e., another JE) that is also continent/conditional in nature (rather than required), and claim 7 does not recite an “administering” that is necessarily/required to be performed (and also recites gene fusions in Tables in manner analogous to claims 2 and 4). Thus, none of claim 5-7 integrates any JE into a practical application or requires anything “significantly more’ than a JE. With further regard to conditional language as set forth in claim 6, it is also noted that the broadest reasonable interpretation (BRI) of a method claim having contingent limitations requires only those steps that must be performed and does not include steps that are not required to be performed because the condition(s) precedent are not met” (MPEP 2111.04(II)); further, “A claim whose BRI covers both statutory and non-statutory embodiments embraces subject matter that is not eligible for patent protection and therefore is directed to non-statutory subject matter” (MPEP 2106.03(II)). Regarding dependent claims 9-11, claim 9 simply provides a further recitation of what a result of detecting “indicates”; this is a recitation of a further type of JE, rather than something “more” or an application of a JE. Claims 10-11 (like claims 2 and 4) reference further gene fusions without clearly adding any further requirements with regard to actions/steps that must be performed (even with regard to the gathering of data/information); thus, the claims do not integrate any JE into a practical application or add anything more than a JE. Dependent claims 12-13 require a “patient sample” but no such sample is necessarily employed in the active steps of claim 8, and the “diagnosing” of claim 12 and further requirements (of administering with regard to a gene fusion/gene variant) of claim 13 are analogous to the further limitations of claims 6-7 (and fail to render the claims patent eligible for the same reasons noted above regarding claims 6-7). Regarding dependent claim 15 and claims dependent therefrom, the ”amplifying” and “detecting” as recited in the claim are addressed above, and the further “detecting…indicates” language is (as discussed above) a further judicial exception. The recitation of fusions/fusion partners in claims 16-17 does not alter the analysis as to the patent eligibility of claim 14, for the same reasons indicated above regarding analogous language in claims 2/4 and 10-11, and the recitation of a sample and “diagnosing” in dependent claims 18-19 similarly does not alter this analysis, for the same reasons indicated above regarding claims 5-7 and 12-13. Finally, claim 20 (which depends from claim 8) recites “treating the patient”, however claim 8 does not recite/require any “patient”; further, the “administering” of the claim, and the reference to a gene fusion/variant fail to render the claims patent eligible, for the same reasons noted above regarding such limitations in claims 7 and 13.
Accordingly, none of claims 1-2 and 4-20 is current directed to patent eligible subject matter.
Claims 8-20 are also rejected under 35 USC 101 because to the extent that the (indefinite) claims are directed to the embodiments noted above that merely require “use of a set of probes” without any required actions/steps (see the language of each of independent claims 8 and 14), the claimed invention is directed to non-statutory subject matter. The claim(s) does/do not fall within at least one of the four categories of patent eligible subject matter because such a claim is not any of a process, machine, manufacture, or composition of matter (and more particularly, the claims cannot be considered as drawn to a method/process without setting forth any steps; see again MPEP 2173.05(q) regarding “use” claims).
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.
While it is noted that the elected species of methods targeting SEQ ID NO: 72, breast carcinoma, and a gene fusion involving partner genes RARA/HOXB3 are under consideration herein, given that some claims presently under consideration also recite additional embodiments – specifically the alternative species of SEQ ID NO: 17, a CEP85L-ROS1 fusion, and glioblastoma – the rejection below is included herein in the interest of compact prosecution.
Claims 1-2, 4-13, and 20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-9 of U.S. Patent No. 10,072,298 (11 Sept 2018; cited herein). Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘298 claims anticipate and/or render obvious embodiments of the instant claims directed to amplifying and detecting a CEP85L-ROS1 fusion of SEQ ID NO: 17; note the recitation in each of independent claims 1 and 8 of the group of sequences of SEQ ID NOS 1-328 as alternatives, as well as the recitation of “CEP85L and ROS1” as gene fusion partners in dependent claims 4 and 11). The embodiment of glioblastoma detection is also embraced by the instant claims (see independent claim 1, 6, 9, and 12), such that both the instant claims and the issued ‘298 claims embrace detection/diagnosis of glioblastoma via the amplifying and detecting of SEQ ID NO: 17. Regarding instant dependent claims 2, 7, 10, and 13, the references to Tables in these claims does not meaningfully further limit what is claimed, and it is noted that the ‘298 claims reciting the use of patient samples as well the treating of patients. Thus, the instant claims (again, as directed to a presently non-elected species) are not patentably distinct from the ‘298 claims.
Conclusion
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/DIANA B JOHANNSEN/Primary Examiner, Art Unit 1682