DETAILED ACTION
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 .
Continued Examination Under 37 CFR 1.114
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 12/29/2025 has been entered.
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, 14-25, 34-38, 81 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 claimed invention is not supported by an enabling disclosure taking into account the Wands factors. In re Wands, 858/F.2d 731, 8 USPQ2d 1400 (Fed. Cir. 1988). In re Wands lists a number of factors for determining whether or not undue experimentation would be required by one skilled in the art to make and/or use the invention. These factors are: the quantity of experimentation necessary, the amount of direction or guidance presented, the presence or absence of working examples of the invention, 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, and the breadth of the claim.
Claims are broadly drawn to methods of treating a subject having decreased bone mineral density, osteopenia or osteoporosis or decreasing KREMEN1 expression in a human subject by administering an inhibitor of Kringle Containing Transmembrane Protein 1 (KREMEN1) to a subject, wherein such inhibitor comprises antisense oligonucleotide, siRNA or shRNA targeting KREMEN1.
Instant claims encompass administration of an inhibitor of KREMEN1 to subjects for treatment of decreased bone mineral density, osteopenia or osteoporosis, wherein such inhibitor comprises antisense oligonucleotide, siRNA or shRNA targeting KREMEN1.
Instant specification, however, does not provide any working examples to treat any of the diseases claimed or to decrease KREMEN1 expression in a human subject with any possible inhibitor of KREMEN1. There is nothing in specification concerning activity of any antisense oligonucleotide, siRNA or shRNA targeting KREMEN1 in any type of cells or any organisms. Specification does not provide any specific examples of any antisense oligonucleotides, siRNAs or shRNAs targeting KREMEN1.
The specification fails to provide guidance on actual treatment of the diseases claimed by an inhibitor of KREMEN1.
The only relevant information related to potential disease treatment is provided in Example 2 showing that subjects with loss-of-function of KREMEN1 have higher bone mineral density. It is noted though that loss of function of a gene is very different from gene inhibition and specification does not provide enough information to find out if the inhibitor of the same gene provides the same effect as the loss of function of the gene. An organism with loss of function of the gene does not produce any such gene products at all such as mRNAs. Antisense oligonucleotides, siRNA or shRNA on the other hand target specific mRNAs and destroy them, so their mechanism of action significantly differs from genetic loss-of-function.
Prior art shows unpredictability in disruption of KREMEN1 to increase bone density. Ellwanger et al (MOLECULAR AND CELLULAR BIOLOGY, 2008, vol.28, no.15, pages 4875–4882, cited from IDS) teach that mice lacking KREMEN1 gene do not show any increase in bone density (see second column on page 4879). Thus, the inhibition of KREMEN1 by antisense oligonucleotides, siRNAs or shRNAs would not be expected to increase bone density.
The guidance provided in the specification is not sufficient and fails to address the issue of how specific inhibitors can be used for treatment of the diseases claimed. There is no prior art teaching any KREMEN1 inhibitors for treatment of the diseases claimed or even simple administration of KREMEN1 inhibitors to human subjects.
In the absence of guidance, undue trial and error experimentation would have been required by one skilled in the art at the time invention was made to identify and administer antisense oligonucleotide, siRNA or shRNA targeting KREMEN1 for treatment of diseases as instantly claimed. Given the breadth of the claims, unpredictability of the art and lack of guidance of the specification, as discussed above, undue experimentation would be required by one skilled in the art to make and use the claimed invention commensurate in scope with the claims.
Response to Arguments
Applicant did not present any specific arguments in the response filed on 11/29/2025.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to EKATERINA POLIAKOVA whose telephone number is (571)270-5257. The examiner can normally be reached Mon-Fri 8-5.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jennifer Dunston can be reached at (571)272-2916. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/EKATERINA POLIAKOVA-GEORGANTAS/Primary Examiner, Art Unit 1637