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 .
Claim Rejections - 35 USC § 112- 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 and 121-127 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 instant claims set forth treating clonal hematopoiesis (CH) with a KNTC1 antagonist that is an antisense, RNAi, or shRNA and hybridizes to a KNTC1 nucleic acid molecule.
Although the specification teaches an association between a single mutation in KNTC1 and mosaic loss of human Y chromosome (mLOY), there is no evidence that the mutation itself is causative of the observed decreased risk for mLOY, and furthermore, mLOY is associated with CH but is not the same as CH. The specification teaches that it is “plausible” that the observed association is related to a loss of function of KNTC1, but provides no evidence to demonstrate that this is so. It is also “plausible” that the polymorphism is simply linked to another polymorphism near or far from it, within KNTC1 or outside KNTCT which is in some way functioning to protect from mLOY. Therefore, it is highly unpredictable, based on the evidence of record whether treatment with a KNTC1 antagonist, even if one were discovered, would prevent or treat mLOY or CH.
Regarding treating CH in general, with any agent, at the time the invention was made, there was no known treatment for CH and no known way to prevent developing CH. There were no known antagonists against KNTC1 available for administration. Wang recognized KNTC1 as having a promotional effect on cervical cancer, and teaches "KNTC1 is a highly potent candidate for becoming a therapeutic target (p. 9505). Even post-filing, Sloan Kettering teaches that there are no known treatments for CH, and Weeks teaches that the field is "primed" for investigations to identify therapeutic interventions that counter the risk of malignant and nonmalignant outcomes of CH.
Developing evidence of a causal relationship between KNTC1 and CH such to support that a KNTC1 antagonist would be functional to treat CH would be highly unpredictable work, and would take an enormous amount of experimentation. There would be no guarantee of success. Likewise, developing any treatment for CH to prevent it or to mitigate outcomes would be an enormous and unpredictable endeavor, noting that even after filing such treatments have not been developed.
Furthermore, with regard to detecting variants that are associated with decreased risk of CH, the specification demonstrates that it is highly unpredictable work which must be undertaken empirically. The specification teaches a single variant with is predictive of mLOY, and does not teach any variant predictive of CH, nor does it provide any guidance of additional variants that could be identified in subjects. The screening for and identifying additional variants would taken an enormous amount of experimentation in a highly unpredictable area where it is unknown if additional associated variants in the gene even exist.
Therefore, having considered all of this, it is concluded that it would require undue experimentation, which is well beyond routine to practice the instantly claimed invention.
Response to Remarks
Rejections which were withdrawn were overcome by amendment of the claims.
Applicant traverses the enablement rejection.
Applicant argues that the claims are sufficiently enabled. Applicant argues that the specification does not need to disclose a causal relationship between KNTC1 and CH. The specification postulates that since a single mutation was observed as being associated with mLOY (not CH), that the mutation may cause decreased risk of mLOY, and then following that inhibition of KNTC1 may prevent clonal hematopoiesis. So, it is entirely relevant whether or not the observed mutation is causative of the observed decreased risk of mLOY, since whether or not it is causative underlies whether or not there is any predictability with regard to the ability to treat, prevent, or reduce clonal hematopoiesis in a human subject. The state of the art at the time of the invention, and even after it did not include any known treatments for CH and no known way to prevent it. Therefore, it is highly unpredictable whether the claimed treatments would function, and there is no evidence of record to support that they will.
Applicant’s remarks regarding inhibitory nucleic acids are not disputed. The rejection regarding the type of inhibitor is withdrawn. However, there remains insufficient evidence to support that such a treatment could treat or prevent CH.
The instant assay is presented in a context where the was no known treatment for clonal hematopoiesis (CH) in a human subject, nor any way known to prevent it.
The instant specification does not provide any evidence to suggest that antagonizing KNTC1 would prevent or treat CH.
The specification provides evidence of a single SNP in CH that is associated with mLOY, and not CH.
The specification does not even assert that the observed SNP causes loss of function, only that it “is plausible”. The examiner’s position in view of this possibility is that it also is possible that it is not the case and it is highly unpredictable which is accurate.
The rejection is maintained and applied to the newly added claims.
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 Juliet Switzer whose telephone number is (571)272-0753. The examiner can normally be reached Monday to Thursday, 8:00 AM-3:30 PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Winston Shen can be reached at (571)-272-3157. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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Juliet Switzer
Primary Examiner
Art Unit 1682
/JULIET C SWITZER/Primary Examiner, Art Unit 1682
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