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 .
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
DETAILED ACTION
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 Dec. 26, 2026 has been entered. All arguments have been fully considered.
Status of the Claims
Claims 9, 10 and 23 are currently pending.
Claims 9, 10 and 23 are amended.
Claims 1-8 and 11-22 are cancelled.
Claims 9, 10 and 23 have been considered on the merits.
Claim Rejections - 35 USC § 112
The claim rejections under 35 USC § 112, (a) or first paragraph (pre-AIA ) for written description and enablement are withdrawn due to amendment.
New claim rejections under 35 USC § 112, (a) or first paragraph (pre-AIA ) for written description and enablement have been added to address the claim amendments.
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 9, 10 and 23 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 claims 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 pre-AIA the inventors, at the time the application was filed, had possession of the claimed invention.
The instant claims are drawn to a method of inhibiting osteoclast differentiation activity and a method for promoting expression of osteoarthritis inducing factors by administering a composition comprising an inhibitor of a COTL1 protein or an inhibitor of a gene encoding the same as an active ingredient to a subject, both of which have a wide array of activities and/or effects. Thus, the claims are broadly drawn to any compound or molecule which acts as an inhibitor of the protein or the gene of COTL1. Therefore, the claims are considered genus claims that encompass a wide array of compounds. The claims encompass any inhibitor of the COTL1 protein or any inhibitor of the gene encoding COTL1 which are not described by their function, structure or relation thereto. The genus for an inhibitor of the COTL1 protein or an inhibitor of the gene encoding COTL1 is highly variant, inclusive to numerous structural variants because a significant number of structural differences between genus members is permitted.
The specification describes:
“the COTL1 inhibitor is an agent that inhibits the expression or activity of the COTL1 protein or the gene encoding the same” (0087 of published application) and
“inhibitor may be selected from the group consisting of antisense nucleotides complementarily binding to COTL1 mRNA, small interfering RNA (siRNA), and
short hairpin RNA (shRNA), or may be selected from the group consisting of antibodies, peptides, aptamers, compounds, and natural products specifically binding to COTL1, but is not limited thereto” (0088 of published application).
The specification does not disclose the diverse genus for an inhibitor of the COTL1 protein or an inhibitor of the gene encoding COTL1. Additionally, the specification does not place any structure, chemical or functional limitations on the embraced by genera of “an inhibitor of the COTL1 protein or an inhibitor of the gene encoding COTL1”. The specification instead states the “COTL1 inhibitor is an agent that inhibits the expression or activity of the COTL1 protein or the gene encoding the same” (0087 of published application). This description does not convey a common structure or function. In sum, specification and the claims do not provide any guidance on the structure of either an “an inhibitor of the COTL1 protein or an inhibitor of the gene encoding COTL1”.
The MPEP states that written description for a genus can be achieved by a representative number of species within a broad generic. It is unquestionable that the claims are broad generics, with respect to all of the potential species of inhibitors that may exhibit one, all, of or any of the claimed activity. The possible variations of compounds are limitless with potentially thousands of compounds that may exhibit the claimed activities. The purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter claimed by them. A patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that the inventor invented the claimed invention. Thus, an applicant complies with the written description requirement "by describing the invention, with all its claimed limitations," and by using "such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention."
The specification lacks sufficient variety of species of compounds to reflect this variance in the genus since the specification does not provide any examples of such a genus of compounds. Accordingly, the specification fails to provide adequate written description for the genera of “an inhibitor of the COTL1 protein or an inhibitor of the gene encoding COTL1” and does not reasonably convey to one skilled in the relevant art that the inventors, at the time the application was filed had possession of the entire scope of the claimed invention. Moreover, the specification neither describes the complete structure of a representative number of species, nor describes a representative number of species in terms of partial structure and relevant identifying characteristics. Absent of such teachings and guidance as to the structure and function of these compounds, the specification does not describe the claimed antagonist in such full, clear, concise and exact terms so as to indicate that Applicant had possession of all substances capable of being an expression promotor or activator of COTL1 at the time of filing of the present application. Thus, the written description requirement has not been satisfied.
Claims 9, 10 and 23 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 claims 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 specification describes that osteoclast differentiation activity is inhibited in osteoclasts isolated from COTL1 knock-out mice compared to normal mice, that the COTL1 knock-out mice had differences in bone structure compared to normal mice (Examples 1 and 2). The specification also describes that inhibiting COTL1 expression in isolated chondrocytes from cartilage increases the expression COX-2, MMP-3 and MMP-13, osteoarthritis inducing factors (Example 3). The specification does not reasonably provide enablement for a method of treating a subject to inhibit osteoclast differentiation activity or to promote the expression of the osteoarthritis inducing factors, COX-2, MMP-3 and MMP-13 by administering a composition comprising an inhibitor of a COTL1 protein or gene encoding the same as an active ingredient to the subject in need of inhibiting osteoclast differentiation activity, or promoting the expression of the osteoarthritis inducing factors, COX-2, MMP-3 and MMP-13, respectively.
The factors to be considered in determining whether a disclosure meets the enablement requirements of 35 U.S.C. 112, first paragraph, have been described in In re Wands, 858 F.2d 731, 8 USPQ2d 1400 (Fed. Cir., 1988). The court in Wands states, “Enablement is not precluded by the necessity for some experimentation, such as routine screening. However, experimentation needed to practice the invention must not be undue experimentation. The key word is ‘undue’, not ‘experimentation’” (Wands, 8 USPQ2sd 1404). Clearly, the enablement of a claimed invention cannot be predicated on the basis of quantity of experimentation required to make or use the invention. “Whether undue experimentation is needed is not a single, simple factual determination, but rather is a conclusion reached by weighing many factual considerations” (Wands, 8 USPQ2d 1404). Among these factors are: (1) the nature of the invention; (2) the breadth of the claims; (3) the state of the prior art; (4) the predictability or unpredictability of the art; (5) the relative skill of those in the art; (6) the amount of direction or guidance presented; (7) the presence or absence of working examples; and (8) the quantity of experimentation necessary.
While all of these factors are considered, a sufficient amount for a prima facie case is discussed below.
(1) The nature of the invention and (2) the breadth of the claims:
The claims are drawn to methods of inhibiting osteoclast differentiation activity or promoting the expression of the osteoarthritis inducing factors, COX-2, MMP-3 and MMP-13 by administering a composition comprising inhibitor of COTL1 protein or a gene encoding COTL1 as an active ingredient to a subject in need of one of the conditions. Thus, the claims taken together with the specification imply that osteoclast differentiation activity can be inhibited or the expression of the osteoarthritis inducing factors, COX-2, MMP-3 and MMP-13 can be promoted in any subject in need thereof by administering in any amount or dosage a composition containing any concentration and formulation of any inhibitor of the COTL1 protein or any gene encoding COTL1.
(3) The state of the prior art and (4) the predictability or unpredictability of the art:
There appears to be no description in the prior art for the claimed methods. Ouyang et al. (CN 110066866) (ref. of record) reports that elevated COTL1 suggests osteoarthritis of a certain type and that COTL1 levels can be used for diagnosing the type of osteoarthritis (background and summary of invention of EPO translation). Jeong et al. (KR 10-197076 B1) (ref. of record) discloses a method of treating blood diseases by administering COTL1 protein or gene encoding for it (abstract and summary of invention). Xia et al. (Oncogene, 2018) reports that COTL1 expression sensitizes breast cancer cells to chemotherapeutic drugs (abstract). Thus, as the state of the art stands, the method would be unpredictable depending on the subject and their condition and the substance being used to act as an expression promoter or activator of COTL1.
(5) The relative skill of those in the art:
The relative skill of those in the art is high.
(6) The amount of direction or guidance presented and (7) the presence or absence of working examples:
The instant specification does not provide any working examples or animal models and does not provide any guidance for the instantly claimed method other than suggesting that osteosclerosis or osteoarthritis can be prevented or treated in a subject by administering a pharmaceutical composition or a health functional food containing a COTL1 protein or gene encoding the same or an expression promoter or activator of COTL1, based on observations made in COTL1 knockout mice and the expression of osteoarthritis inducing factors when COTL1 is inhibited in isolated chondrocytes (0038 and 0083-0085 of published application). The specification provides evidence that the down regulation of the COTL1 protein inhibits the differentiation activity of osteoclasts which reinforces bone density and increases the factors, COX-2, MMP-3 and MMP-13, that induce articular inflammation and cartilage degeneration (abstract and Examples 1-3). In addition, the specification reports that the differentiation activity of osteoclasts is reduced when the expression of the COTL1 protein or gene is reduced which results in increase bone density and the expression of Cox-2, MMP-3 and MMP-13 (0060).
Specifically, Example 1 discloses that osteoclast differentiation activity is inhibited in COTL1 knock-out mice as shown by reduced TRAP activity in osteoclasts isolated from the COTL1 knock-out mice compared to normal mice. Example 2 discloses that the bone density of COTL1 knock-out mice had higher bone mineral density and increased density of bone microstructures compared to normal mice. In addition, the COTL1 knock-out mice had increased % bone volume and trabecular number compared to normal mice, and low trabecular spacing compared to normal mice. Example 3 discloses that inhibiting COTL1 expression in isolated chondrocytes from cartilage increases the expression of COX-2, MMP-3 and MMP-13, osteoarthritis inducing factors.
Based on these observations, it appears that applicant is speculating that osteoclast differentiation activity can be decreased in a subject, and the osteoarthritis inducing factors, COX-2, MMP-3 and MMP-13, can be increased in a subject by inhibiting COTL1 protein or COTL1 gene expression in the subject (0110-0118 of published specification). This does not prove enablement for inhibiting of osteoclast differentiation activity or the increasing of the expression of COX-2, MMP-3 and MMP-13 in a subject. Observations in a COTL1 knockout mouse and a chondrocyte cell culture does not reasonably predict that the claimed method would be effective, since there is nothing in the disclosure that shows that by inhibiting COTL1 protein or COTL1 gene expression in a subject results in inhibition of osteoclast differentiation activity, and the promotion of the expression of COX-2, MMP-3 and MMP-13. There is nothing of record that shows inhibiting COTL1 in the subject would actually result in any of these claimed effects.
The specification does not describe what amount of the pharmaceutical composition would be required for achieving the claimed results. There general directions on determining the effective dose and a description of factors that would change the effective dose such as the purpose of use, the age, sex, weight, health status of the patient, etc., but no clear suggested dosages or working examples for inhibiting osteoclast differentiation activity or promoting COX-2, MMP-3 and MMP-13 expression with the claimed substances (0097-0098 of published application).
There is no detailed description or examples in the specification for the administration of a pharmaceutical composition comprising an inhibitor of the COTL1 protein or the gene encoding COTL1 for inhibiting osteoclast differentiation activity or promoting COX-2, MMP-3 and MMP-13 expression in a subject. There is no description of the required dosage or amount of the pharmaceutical composition to be administered and no description of the mode of administration of the pharmaceutical composition.
Therefore, there is no conclusive evidence in the instant disclosure to indicate that the instantly claimed methods can be used to inhibit osteoclast differentiation activity or promote COX-2, MMP-3 and MMP-13 expression in a subject.
(8) The quantity of experimentation necessary:
Considering the state of the art as discussed above and the high unpredictability and the lack of guidance provided in the specification, one of ordinary skill in the art would be burdened with undue experimentation to use the claimed invention as instantly claimed. Therefore, the claims are rejected under 35 U.S.C. 112, first paragraph, for a lack of enablement.
Response to Arguments
Applicant's arguments filed Dec. 10, 2026 have been fully considered but they are not persuasive.
With respect to the rejections under 35 U.S.C. § 112 (a) written description, Applicant argues that the claim 9 has been amended to subject matter which sufficiently described and enabled in the specification on pgs. 1, 4-5, 16, 21-23 and in Examples 1-3 (Remarks pg. 4 para. 2-3 and 5). The previous rejections under 35 U.S.C. § 112 (a) written description have been withdrawn due to amendment.
Applicant argues that sufficient description has been provided defining COTL1 inhibitors (Remarks pg. 4 para. 4). However, this argument was not found to be persuasive, and new rejections under 35 U.S.C. § 112 (a) written description have been added due to amendment. Briefly, as explained the new rejection, there is no adequate description for what is encompassed by the genus of an inhibitor of a COTL1 protein or a gene encoding a COTL1 protein.
With respect to the rejections under 35 U.S.C. § 112 (a) enablement, Applicant argues that the claims have been amended to subject matter which sufficiently described and enabled in the specification and that there is detailed guidance on COTL1 inhibitors (Remarks pg. 5 last para.). Specifically, Applicant argues that Examples 1-3 provide clear working models of knockout mice and isolated cells demonstrating that inhibiting COTL1 inhibits osteoclast differentiation and increases bone density and promotes osteoarthritis inducing factor expression (Remarks pg. 6 para. 1). In addition, Applicant argues that these models provide a reasonable expectation of success of the claimed invention and that the art is not unpredictable for using inhibitors to mimic knockout effects (Remarks pg. 6 para. 2). However, these arguments were not found to be persuasive, as explained in the new rejections under 35 U.S.C. § 112 (a). The Applicant’s amendments changing the methods of claims 9, 10 and 23 necessitated the withdrawal of previous rejections and new rejections 35 U.S.C. § 112 (a).
Conclusion
No claims are allowed.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to EMILY ANN CORDAS whose telephone number is (571)272-2905. The examiner can normally be reached on M-F 9:00-5:30 EST.
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/EMILY A CORDAS/Primary Examiner, Art Unit 1632