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 .
The finality of the action mailed 7/8/2026 has been withdrawn.
Election/Restrictions
Applicants’ election without traverse of Group I, claims 21-27 and the gene IKZF1 in claim 21 along with the gene of claim 22 in the reply filed on 29 September 2025 is acknowledged. Claims 23-24 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. The search and examination was extended to the BTG2 gene.
Application Status
The Amendments and Remarks filed 202 September 2026 in response to the Office Action 08 July 2026 are acknowledged and have been entered. Claims 21 and 36 are amended and claims 1-20, 28-35, 37-39 have been cancelled. Claims 21-27 and 36 are pending. Claims 23 and 24 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species. Claims 21-22, 25-27, and 36 are being examined on the merits.
Priority
This application is a 371 PCT of KR2021/008524 filed 07/05/2021. Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d).
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 21-22, 25-27, and 36 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 claim(s) 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
MPEP 2163.II.A.3.(a).i) states, “Whether the specification shows that applicant was in possession of the claimed invention is not a single, simple determination, but rather is a factual determination reached by considering a number of factors. Factors to be considered in determining whether there is sufficient evidence of possession include the level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention”.
For claims drawn to a genus, MPEP § 2163 states the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
Claim 21 is directed to a method of preventing or treating gastric cancer in a subject in need thereof by administering a composition comprising an inhibitor of expression of IKZF1 or a nucleotide of IKZF1 as an active ingredient. Claim 36 is directed to a method for suppressing metastasis or recurrence of gastric cancer in a subject in need thereof, comprising a step of administering a composition comprising, an inhibitor of the expression of IKZFl, or a nucleotide of IKZFl, as an active ingredient.
The claim encompasses two distinct active-ingredient alternatives: an inhibitor of IKZF1 expression and a nucleotide of IKZF1. The latter alternative encompasses a single nucleotide of IKZF1 and does not require that the nucleotide inhibit IKZF1 expression. Possession of these claims requires the possession of the genus of inhibitors that function to inhibit the IKZF1’s expression and single nucleotides where each function in preventing or treating all cancers. The specification does not provide a representative number of species sufficient to demonstrate possession of the claimed genus of inhibitors of IKZF1 expression.
The current specification, as filed, discloses that ‘The inventors of the present disclosure have found out that, although it is effective to inhibit the production of circulating tumor cells to interrupt this process called distant metastasis, if circulating tumor cells have already been produced and have invaded into blood vessels, it is more effective to artificially maintain the suspension phenotype to prevent the attachment of the cells to the secondary sites. Accordingly, if the presence of CTCs in vivo has been detected, the colonization of the produced circulating tumor cells can be prevented and, ultimately, the formation of metastatic cancer can be interrupted effectively by overexpressing the 20 genes that confer suspension phenotype to cells or inhibiting the 18 genes that confer adherent phenotype’ (pg. 11, last paragraph – 12, para 1). The specification also discloses that ‘ measuring the mRNA expression of several AST factors in the CTC-like cells of MDA-MB-231, SUIT2 and AGS cells’ (see Knockdown of AST factors in cancer cell and inhibition of CTC production, lines 12-13). The specification identifies IKZF1 among a group of adhesion-to-suspension transition (AST) factors and generally describes compositions comprising inhibitors of expression of selected target genes ([0012], [0015]–[0021]). The specification further describes the proposed use of AST-factor inhibition to suppress circulating tumor cell production and metastatic processes ([0032]–[0035], [0061]–[0070]). However, the specification does not identify a single nucleotide of IKZF1 that is capable of preventing or treating gastric cancer, nor a representative number of inhibitors that can inhibit IKZF1. The disclosure of the IKZF1 gene or its nucleotide sequence does not establish possession of a therapeutic method employing an individual constituent nucleotide as an active ingredient. The specification provides neither a representative operative single-nucleotide species nor a structure-function relationship establishing how a single nucleotide of IKZF1 would produce the claimed therapeutic effect. Furthermore, the specification does not disclose inhibiting IZKF1 gene expressions in gastric cancer CTC, or preventing or treating cancer by inhibiting IZKF1 gene expressions in gastric cancer.
Although the specification identifies IKF1 as an AST factor, generally contemplated inhibition of expression of selected target genes, and discusses categories of agents capable of inhibiting gene expression , the claimed genus is defined principally by the results to be achieved, i.e., inhibition of IKZF1 expression together with the claimed therapeutic effect – rather than by common structural characteristics. The specification does not disclose a representative collection of structurally diverse IKZF1 inhibitors spanning the scope of the genus, such as specifically identified siRNAs, shRNAs, or antisense oligonucleotides antibodies, small molecules, or other structurally defined agents, each demonstrated or shown to inhibit IKZF1 and possess the claimed therapeutic activity. The specification only teaches SEQ ID NO: 6 as the AST factor of the gene IKZF1 and an anti-lKZF1; however these disclosures does not supply a representative structural species common to for the claimed genus. The claimed genus encompass structurally unrelated agents operating through materially different mechanism, and the disclosure provides neither a representative number of species across the structural diversity not identifying structural characteristics correlated with the claimed function.Regarding the genetic inhibition, Seth (Seth et al. Therapeutic delivery 3.2 (2012): 245-261) teaches insufficient tumor biodistribution, poor cellular uptake, endosomal escape, unintended off-target effects, and toxicity as obstacles to developing effective siRNA-based cancer therapeutics [abstract]. Sibley (Sibley et al. www.moleculartherapy.org vol. 18 no. 3, 466–476. 2010) teaches exogenous gene-silencing strategies (RNAi) [pg. 468-469] and new generation of RNA-based silencing approaches [Table 1]. Sibley teaches off-target effects, toxicity due to saturation of the endogenous RNAi functions, limited duration of silencing, and effective targeted delivery are still concerns as it relates to RNAi technology [abstract]. Smith (Smith et al. PLoS Biol. 2017 Nov 30;15(11):e200321) analyses types of genetic perturbations, RNAi and CRISPR, in which both are used to generate loss-of-function [author summary]. Smith teaches that the off-target effects of RNAi are much greater than typically appreciated, whereas CRISPR technology has negligible off-target activity [author summary]. Smith further teaches that that the RNAi machinery includes the use of either siRNAs or shRNAs [pg. 2, para 3]. Lavorgna (Lavorgna et al. Pharmacological Research 110 (2016) 131–138) teaches strategies for targeting long ncRNAs which includes the use of RNAi (siRNA) technology, antisense oligonucleotides (AONs) [pg. 134, 3], zinc finger nuclease (ZFN), transcription activation-like element nuclease (TALEN) and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) system [pg. 135, 3.3]. Segara (US 2006/0269921 A1) teaches that ribozymes can also be used to inhibit transcription of nucleic acid sequences [0627].
Furthermore, although the specification identifies IKZF1 as an AST factor and describes experimental investigation of AST-factor expression and knockdown as discussed above, the disclosed results do not establish that the inventors possessed a method of preventing or treating gastric cancer using the full range of IKZF1 inhibitors encompassed by claims 21 and 36. The disclosure concerning CTC-related phenotypes does not, without additional supporting information, establish possession of a method for preventing primary gastric cancer or treating established gastric cancer using a single nucleotide of IKZF1.
Claim 22 requires the composition to comprise an inhibitor of expression of BTG2 and therefor introduces an additional, independently broad functional genus. The specification’s identification of BTG2 as an AST-related target, SEQ ID NO: 2, anti-BTG2, and general contemplation of inhibiting its expression foes not itself describe the genus of BTG2-expression inhibitors. The specification does not disclose a representative collection of structurally diverse BTG2 inhibitors spanning the scope of the genus, such as specifically identified siRNAs, shRNAs, or antisense oligonucleotides antibodies, small molecules, or other structurally defined agents, or identify structural characteristics common with inhibition of BTG2 expression, shown to inhibit BTG2 and possess the claimed therapeutic activity. Accordingly claim 22 require selection of an operative member from a second broad genus defined by the desired result, while the disclosure identified BGT2 as a target and envisions provision of an agent capable of inhibiting its expression; thereby not curing the deficiency of the parent claim.
Claim 25 requires the composition comprising the claimed IKZF1 inhibitor or nucleotide to inhibit production of circulating tumor cells, while claim 27 requires the composition to inhibit colonization of the produced circulating tumor cells. Thus, the relevant genus is not merely every agent capable of inhibiting IKZF1 expression, but those members that additionally produce the specified downstream CTC-related therapeutic effects. The specification does not provide a representative number of structurally identified IKZF1 inhibitors or individual IKZF1 nucleotides demonstrated to satisfy these additional functions, not does it disclose structural characteristics correlated with inhibition of CTC production or colonization that would permit one skilled in the art to recognize other members possessing those functions. The additional function limitations therefore further narrow the required functional subset without supplying the missing structural description and do not cure the deficiency of the parent claim.
Accordingly, the specification fails to reasonably convey to one of ordinary skill in the art that the inventors were in possession of the full scope of the claimed method as of the effective filing date.
Claims 21-22, 25-27, and 36 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.
Nature of the Invention
Claim 21 is directed to a method of preventing or treating gastric cancer in a subject in need thereof by administering a composition comprising an inhibitor of expression of IKZF1 or a nucleotide of IKZF1 as an active ingredient. Claim 36 is directed to a method for suppressing metastasis or recurrence of gastric cancer in a subject in need thereof, comprising a step of administering a composition comprising, an inhibitor of the expression of IKZFl, or a nucleotide of IKZFl, as an active ingredient. Claims 22, and 25- 27 is directed to the method of claim 21 where the composition further comprises expression inhibitors of BTG2, where the composition inhibits the production of circulating tumor cells (CTC), produces CTCs and inhibits the colonization of the produced CTC, respectively. Enablement of the claims turns on whether one of ordinary skill in the art could prevent or treat gastric cancer by inhibiting IKZF1 with an inhibitor or a nucleotide of IZKF1 without undue experimentation.
State of the Art
Seth (Seth et al. Therapeutic delivery 3.2 (2012): 245-261) teaches insufficient tumor biodistribution, poor cellular uptake, endosomal escape, unintended off-target effects, and toxicity as obstacles to developing effective siRNA-based cancer therapeutics [abstract]. Sibley (Sibley et al. www.moleculartherapy.org vol. 18 no. 3, 466–476. 2010) teaches exogenous gene-silencing strategies (RNAi) [pg. 468-469] and new generation of RNA-based silencing approaches [Table 1]. Sibley teaches off-target effects, toxicity due to saturation of the endogenous RNAi functions, limited duration of silencing, and effective targeted delivery are still concerns as it relates to RNAi technology [abstract]. Smith (Smith et al. PLoS Biol. 2017 Nov 30;15(11):e200321) analyses types of genetic perturbations, RNAi and CRISPR, in which both are used to generate loss-of-function [author summary]. Smith teaches that the off-target effects of RNAi are much greater than typically appreciated, whereas CRISPR technology has negligible off-target activity [author summary]. Smith further teaches that that the RNAi machinery includes the use of either siRNAs or shRNAs [pg. 2, para 3]. Lavorgna (Lavorgna et al. Pharmacological Research 110 (2016) 131–138) teaches strategies for targeting long ncRNAs which includes the use of RNAi (siRNA) technology, antisense oligonucleotides (AONs) [pg. 134, 3], zinc finger nuclease (ZFN), transcription activation-like element nuclease (TALEN) and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) system [pg. 135, 3.3]. Segara (US 2006/0269921 A1) teaches that ribozymes can also be used to inhibit transcription of nucleic acid sequences [0627]. Accordingly, successful inhibition of IKZF1 in an experimental system would not necessarily establish that the same inhibitor, or other structurally distinct inhibitors encompassed by the claims, would prevent or treat gastric cancer or suppress its metastasis or reoccurrence in a subject.
Breadth of the claims
The claims are broadly drawn to preventing or treating any type of cancer in any type of subject by administering either (i) any inhibitor of expression of IKZF1 of any structure; or (ii) a nucleotide of IKZF1. Furthermore, the claims encompass the administration of any inhibitor of BTG2 for the same purpose.
Guidance of the Specification
The specification discloses that ‘The inventors of the present disclosure have found out that, although it is effective to inhibit the production of circulating tumor cells to interrupt this process called distant metastasis, if circulating tumor cells have already been produced and have invaded into blood vessels, it is more effective to artificially maintain the suspension phenotype to prevent the attachment of the cells to the secondary sites. Accordingly, if the presence of CTCs in vivo has been detected, the colonization of the produced circulating tumor cells can be prevented and, ultimately, the formation of metastatic cancer can be interrupted effectively by overexpressing the 20 genes that confer suspension phenotype to cells or inhibiting the 18 genes that confer adherent phenotype’ (pg. 11, last paragraph – 12, para 1). The specification also discloses that ‘ measuring the mRNA expression of several AST factors in the CTC-like cells of MDA-MB-231, SUIT2 and AGS cells’ (see Knockdown of AST factors in cancer cell and inhibition of CTC production, lines 12-13).
The specification identifies IKZF1 among a group of adhesion-to-suspension transition (AST) factors and generally describes compositions comprising inhibitors of expression of selected target genes ([0012], [0015]–[0021]). The specification further describes the proposed use of AST-factor inhibition to suppress circulating tumor cell production and metastatic processes ([0032]–[0035], [0061]–[0070]). The disclosure principally concerns inhibition of CTC-related phenotypes and suppression of metastatic processes. However, the specification does not demonstrate that administration of an IKZF1 expression inhibitor prevents the development of gastric cancer, treats established gastric cancer, or suppresses metastasis or the recurrence of cancer in a subject. The disclosure of IKZF1 expression and its association with AST-related cellular phenotypes does not, by itself, establish that inhibition of IKZF1 will achieve the claimed therapeutic results. Furthermore, the specification does not disclose inhibiting IZKF1 gene expressions in gastric cancer CTC, or preventing or treating cancer by inhibiting IZKF1 gene expressions in gastric cancer. Therefore, the specification fails to establish an operative gastric-cancer prevention, treatment or supression method using the broadly claimed IKZF1 expression inhibitors as claimed.
Moreover, claims 21 and 36 alternatively encompasses administration of a single nucleotide of IKZF1 as an active ingredient. The specification does not identify an operative single-nucleotide therapeutic agent, describe a mechanism by which an individual nucleotide would prevent or treat gastric cancer, or provide experimental results establishing such therapeutic activity. The disclosed methods for inhibiting gene expression using nucleic-acid-based agents do not establish that an individual nucleotide of IKZF1 is capable of performing the same function. A single nucleotide does not inherently possess the sequence-specific recognition properties of an antisense oligonucleotide or siRNA. Accordingly, the specification fails to provide sufficient guidance for practicing the single-nucleotide therapeutic alternative. In the absence of enabling knowledge in the prior art, identifying an operative single-nucleotide agent and establishing its ability to prevent, treat, or supress gastric cancer would require undue experimentation.
Experimentation Required
In order to practice the claimed invention, an immense amount of experimentation would be required. To practice the invention as broadly claimed, it would be necessary for one of ordinary skill in the art to systematically test every IZKF inhibitor known or predicted, or IKZF1 nucleotide against every known form of gastric cancer and its stages to determine which if each inhibitor or nucleotide is capable of preventing cancer, treating cancer, suppressing metastasis, or suppressing the reoccurrence of cancer. However, such experimentation would be highly unpredictable in view of the prior art. Accordingly, practicing the invention would require a massive amount of highly unpredictable experimentation.
Taking into consideration the factors outlined above, including the nature of the invention, the breadth of the claims, the state of the art, the guidance provided by the applicant and the specific examples, it is the conclusion that an undue experimentation would be required to make and use the invention as claimed.
Conclusion
No claims allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to TIFFANY N GROOMS whose telephone number is (571)272-3771. The examiner can normally be reached M-F 830-530.
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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.
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/TIFFANY NICOLE GROOMS/Examiner, Art Unit 1637
/Jennifer Dunston/Supervisory Patent Examiner, Art Unit 1637
