Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
DETAILED ACTION
This action is in response to papers filed 10/29/2025.
Applicant's election without traverse of DDX58 CCL4 IRF1 PSMB10 KLRC2 for IM subtype and COBL EN1 MYBL1 RAD21 ROPN1 S100A1 for B1 subtype in the reply filed on 7/7/2025 is acknowledged. The requirement is still deemed proper and is therefore made FINAL. It is noted that the applicant has deleted the elected combination and as such the next species will be examined.
3. Claims 1-18, 20are pending. Claim 19 has been cancelled.
4. Claims are 5,7,9-17,20 are withdrawn as being drawn to a nonelected invention or species.
5. The following rejections for claims 1-4, 6, 8, 18 are modified necessitated by amendments or newly applied as necessitated by amendment. Response to arguments follows.
6. This action is FINAL.
Withdrawn objections and Rejections
The objection to the claims are withdrawn based upon cancellation of the claims.
The 35 USC 101 and 103(a) rejections made in the previous office action are withdrawn based upon cancelation of claim 19.
The claim rejection under 35 USC 112d made in the previous office action is withdrawn based upon amendments to the claims.
Maintained Improper Markush Grouping
7. Claims 1-4,6,8,18 are rejected under the judicially approved ‘‘improper Markush grouping’’ doctrine. (See Federal Register, Vol. 76, No. 27, Wednesday, February 9, 2011, page 7166). This rejection is appropriate when the claim contains an improper grouping of alternatively useable species. See In re Harnisch, 631 F.2d 716, 719–20 (CCPA 1980). A Markush claim contains an ‘‘improper Markush grouping’’ if: (1) the species of the Markush group do not share a ‘‘single structural similarity,’’ or (2) the species do not share a common use. Members of a Markush group share a ‘‘single structural similarity’’ when they belong to the same recognized physical or chemical class or to the same art-recognized class. Members of a Markush group share a common use when they are disclosed in the specification or known in the art to be functionally equivalent. See MPEP § 803.02.
Here each species is considered to be a method for determining the TNBC subtype from the expression of one or more genes...wherein the one or more genes are selected from the group consisting of AIM2, ALOX5Ap...and combinations therefore".
The recited alternative species in the groups set forth here do not share a single structural similarity, as each method relies on detection of different genes or gene combinations. Each gene that could be detected is itself located in a separate region of the genome and has its own structure. The nature of gene expressions is that they are differences within a population. The genes recited in the instant claims, and the methods which detect them, do not share a single structural similarity since each consists of a different location on human chromosome. The only structural similarity present is that all detected positions are part of nucleic acid molecules. The fact that the genes comprise nucleotides per se does not support a conclusion that they have a common single structural similarity because the structure of comprising a nucleotide alone is not essential to the common activity of being correlated with TNBC subtype. Accordingly, while the different genes are asserted to have the property of being indicative of TNBC subtype, they do not share a single structural similarity.
Following this analysis, the claims are rejected as containing an improper Markush grouping.
Response to Arguments
The reply traverses the rejection. A summary of the arguments is provided below with response to arguments following.
The reply asserts that the claims have been amended to limit the genes of particular subtypes (p. 10-11). The reply asserts that the members share a single structural similarity (p. 10). This argument has been reviewed but have not been found persuasive. These arguments have been considered but have not been found persuasive.
The MPEP directs that it must be clear from their very nature or from the prior art that all of them possess this property. The reply asserts that the genes are all similar based upon the particular subtypes. However, the structural argument of being a particular subtype is not clear from the very nature of the recited genes. For example CCL4 structure does not provide that it is a particular subtype and it’s not clear from the prior art that the gene has this particular property. As such the Markush rejection has been maintained.
Modified Claim Rejections - 35 USC § 112
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 1-4,6,8,18 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 detection of expression, does not reasonably provide enablement for methods of determining and treating a TNBC subtype. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make or use the invention commensurate in scope with these claims. There are many factors to be considered when determining whether there is sufficient evidence to support that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is undue. These factors have been described by the court in re Wands, 8 USPQ2d 1400 (CA FC 1988). Wands states at page 1404,
"Factors to be considered in determining whether a disclosure would require undue experimentation have been summarized by the board in the Ex parte Forman. They include (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims."
The nature of the invention and the breadth of the claims:
The claims are drawn to a method of determining and treating TNBC subtype comprising determining increased expression of CCL4 is associated with TNBC IM subtype and treating with an immune checkpoint inhibitor. Further, claim 18 is drawn to determining that TNBC subtype is not IM and then determining if the TNBC subtype is BL! By determining increased expression of ART3.
The specification does not provide guidance for the claimed method based upon the recited genes for each subtype.
Specification
The specification asserts that TNBC IM subtype is based of increases expression of one or more genes (p. 18). The specification teaches cells lines (p. 24) and humans (examples) but does not teach increased expression and association of TNBC subtype IM. Further the claims are drawn to particular genes that are not provided in the specification to be increased in expression for a particular subtype. For example, the instant specification does not teach PSMB10 is associated with TNBC IM. Further for BL1 the instant specification does not provide the genes of PGBD5 or TP53BP2.
State of the art
The art does not provide the TNBC IM or BL1 subtypes.
The level of skill in the art:
The level of skill in the art is deemed to be high.
Quantity of experimentation necessary:
In order to practice the invention as claimed, one would first have to establish that a predicative relationship exists between the increased expression of the claim genes and subtype, however, the specification does not provide support for these correlations.
Therefore, in light of the breadth of the claims, the lack of guidance in the specification, the high level of unpredictability in the associated technology, the nature of the invention, the negative teachings in the art, and the quantity of unpredictable experimentation necessary to practice the claimed invention, it would require undue experimentation to practice the invention as claimed.
Response to Arguments
The reply traverses the rejection. A summary of the arguments is provided below with response to arguments following. The reply asserts that the claims have been amened (p. 11) however the new combination of genes is not taught in the specification as being increased expression and associated with particular subtypes.
Newly Applied 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 1-4, 6, 8, 18 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 1-4, 6 and 8 are indefinite over the steps of claim 1. In particular step a requires determining expression of at least one gene, however, the wherein clauses in step e requires determination of increased expression of at least one gene associated with TNBC IM and at least one gene associated with TNBC LAR. It is unclear how to perform step e to determine subtype of IM and LAR wherein step A only requires one gene. Therefore the metes and bounds are unclear.
Claim 18 is indefinite as step a only requires the determining expression of one gene. Step d requires determining if the TNBC subtype is BL1, BL2, M or MSL, however, it is not clear how to perform this determining subtype based upon determining expression of only one gene. Therefore the metes and bounds are unclear.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KATHERINE D SALMON whose telephone number is (571)272-3316. The examiner can normally be reached 9-530.
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/KATHERINE D SALMON/Primary Examiner, Art Unit 1682