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 .
Claims Status
Claims 1-12 are pending.
Claims 5-8 are amended.
Election/Restrictions
Applicant’s election without traverse of Group II (claims 5-8) in the reply filed on 04/23/2026 is acknowledged.
Claims 1-4 and 9-12 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected subject matter, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 04/23/2026.
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.
(previous rejection, maintained) Claims 5-8 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.
With regards to claim 5 (and claims 6-8 dependent on), claim 5 recites “wherein the amino acid sequence of the polypeptide is SEQ ID NO: 1”. It is unclear to which polypeptide is “the polypeptide is SEQ ID NO:1” referring to (The RIP3 polypeptide or polypeptide formed by TAT and methylated RIP3?). Therefore, the claim is rendered indefinite.
With regards to claim 5 (and claims 6-8 dependent on), claim 5 recites “wherein a 479th arginine of RIP3 is subjected to symmetric di-methylation modification”. It is unclear to what the 479th arginine is as SEQ ID NO:1 consists of only 26 residues. (Is the 479th arginine residue 479 of RIP3?). Therefore, the claim is rendered indefinite.
Response to Arguments
Applicant's arguments filed 07/06/2026 have been fully considered but they are not persuasive.
In the rejection of the office action of 05/14/2026, with regards to claim 5 (and claims 6-8 dependent on), claim 5 recites the amino acids sequence of the polypeptide is SEQ ID NO: 1”. The rejection was based on the reasoning that It is unclear to which polypeptide is “the polypeptide is SEQ ID NO:1” referring to (The RIP3 polypeptide or polypeptide formed by TAT and methylated RIP3?). In the Applicant Arguments/Remarks Made in an Amendment, applicant has amended the claim to clarify that the SEQ ID NO: 1 refers to the polypeptide formed by connecting the cell-penetrating peptide TAT and the methylated RIP3 polypeptide (see pg. 4 and amended claim 5). Therefore, this part of the rejection has been clarified.
However, Applicant argues that in response to the Office’s further remarks on claim 5 that it is unclear what is meant by “a 479th arginine of RIP3” SEQ ID NO: 1 consists of only 26 residues, the Applicant submits that the 479th arginine is the the 479th arginine residue 479 of RIP3, and not to residue 479 withing SEQ ID NO: 1. Applicant argues that this is consistent with paragraph (0011) which states that the 479th arginine of RIP3 protein is subjected to symmetric di-methylation modification, and with paragraph (0037) and Table 1, which explain that the synthesized peptides are peptide fragments corresponding to the arginine at the 479th position in RIP3.
The Examiner does not find the argument persuasive. Amended claim 5 recites “a methylated Receptor-Interacting Protein Kinase 3 (RIP3) polypeptide, wherein a 479th arginine of RIP3 is subjected to dissymmetric di-methylation modification, and wherein the polypeptide formed by connecting the cell-penetrating peptide TAT and the methylated RIP3 polypeptide has the amino acid sequence shown in SEQ ID NO: 1. It remains unclear, according to the recited claim, to what a 479th arginine is in the methylated peptide as SEQ ID NO:1 consists of only 26 residues. Additionally, SEQ ID NO: 1 has more than one arginine. Therefore, the claim fails to particularly point out and distinctly claim the subject matter which the applicant regards the invention. Although the claims are examined in the light of the specification, the specification cannot be read into the claims, i.e., the limitation of the specification cannot be read into the claims (see MPEP 211 R-5).
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.
(previous rejection, withdrawn) Claims 5-8 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 treatment of cell necroptosis in mouse epithelial cells, does not reasonably provide enablement for preventing and treating diseases caused by cell necroptosis. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
To be enabling, the specification of the patent application must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557, 1561 (Fd. Cir. 1993). Explaining what is meant by “undue experimentation,” the Federal Circuit has stated that:
The test is not merely quantitative, since a considerable amount of experimentation is permissible, if it is merely routine, or if the specification in question provides a reasonable amount of guidance with respect to the direction in which experimentation should proceed to enable the determination of how to practice a desired embodiment of the claimed invention. PP v. Gaurdian, 75 F.3d 1558, 1564 (Fed Cir. 1996). As pointed out by the court in In re Angstadt, 537 F.2d 498 at 504 (CCPA 1976), the key word is “undue”, not ‘experimentation”.
Factors to be considered in determining whether undue experimentation is required, are set forth In re Wands (858 F.2d 731, 8 USPQ 2nd 1400 (Fed. Cir. 1988)) as follows: (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence 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 claim(s).
These factors are always applied against the background understanding that scope of enablement varies inversely with the degree of unpredictability involved. In re Fisher, 57 CCPA 1099, 1108, 427 F.2d 833, 839, 166 USPQ 18, 24 (1970). Keeping that in mind, the Wands factors are relevant to the instant fact situation for the following reasons:
1. The nature of the invention, state and predictability of the art, and relative skill of those in the art
The invention is drawn to the use of a medicine comprising a polypeptide to treat or prevent diseases caused by cell necroptosis. Claims 5-8 are drawn to a method of preventing and treating diseases caused by cell necroptosis in a subject in need thereof, comprising administrating to the subject an effective amount of a medicine containing a polypeptide and one or more pharmaceutically acceptable adjuvants.
The specification defines “treatment” and “prevention” as administrating a medicine comprising a polypeptide to increase resistance of cells to necroptosis.
The relative skill of those in the art is high, generally that of a M.D. or Ph.D. The artisan using Applicant’s invention would generally be a physician with a M.D. degree and several years of experience.
The factor is outweighed, however, by the unpredictable nature of the art. It is well established that “the scope of enablement varies with the degree of unpredictability of the factors involved” and physiological activity is considered to be an unpredictable factor. See In re Fisher, 166 USPQ 18, at 24 (In cases involving unpredictable factors, such as most chemical reactions and physiological activity, the scope of enablement obviously varies inversely with the degree of unpredictability of the factors involved); Nationwide Chemical Corporation, et al., v. Wright, et. al., 192, USPQ 95 (one skilled in chemical and biological arts cannot always reasonably predict how different chemical compounds and elements might behave under varying circumstances); Ex parte Sudilovsky 21 USPQ2d 1702 (Applicant’s invention concerns pharmaceutical activity. Because there is no evidence of record of analogous activity for similar compounds, the art is relatively unpredictable).
At the time of the instant application was filed, the state of the art in treating and preventing diseases caused by cell necroptosis as recited in claim 5 embraces treatment and prevention of the following unrelated diseases (without limitation because the claim is open-ended and embraces any disease caused by cell necroptosis); nerve system disease, cardiovascular diseases, pulmonary diseases, liver diseases, enteric diseases, joint diseases, cancers, infections, renal diseases and skin diseases which are extremely unpredictable and difficult to treat and prevent (Liu et al., MedComm, Vol. 2, pg. 730-755; published December 20, 2021; see Tables 1-2, pg. 735-737) and not enabled by the disclosure. Preventing diseases requires identifying those patients who will acquire the condition before the symptoms occur. This would require extensive and potentially open-ended research on healthy subjects (see Dai et al. International Journal of Molecular Medicine, Vol. 47:89; published May 2021; also see Table 2, pg. 10 in Chaouhan et al., International Journal of Molecular Sciences, Vol. 23:12714; published October 22, 2022).
2. The breadth of the claims
Claims 5-8 are very broad in terms of the type of disease being treated and prevented. With regards to claim 5, all diseases caused by cell necroptosis (see pg. 113, Figure 2 in Galluzi et al., Annual Review of Pathology, Vol. 12, pg. 103-130; published January 24, 2017) are claimed to be prevented and treated by the medicine comprising the polypeptide.
3. The amount of direction or guidance provided and the presence or absence of working examples
The specification provides examples for treating cell necroptosis in mouse intestinal epithelial cells but does not provide any data that shows that the medicine comprising the polypeptide in claim 5 is useful for treating and preventing any disease caused by cell necroptosis in man or animal.
4. The quantity of experimentation
Because of the known unpredictability of the art (as discussed supra) and in the absence of experimental evidence commensurate in scope of the claims, the skilled artisan would not accept that the medicine comprising the polypeptide described in claim 5 could be predictably used for prevention and treatment for all diseases caused by cell necroptosis.
Determining if a particular compound will treat or prevent any particular disease state would require formulation into a dosage form, and subjecting into clinical trials or testing in an assay known to correlate to clinical efficacy of such treatment (see Wang et al., arXiv:2412.09378v3; published January 3, 2026). This is undue experimentation given the limited guidance and direction provided by Applicants.
Accordingly, the inventions of claims 5-8 do not comply with the scope of enablement requirement of 35 U.S.C. 112, first paragraph, since to practice the claimed invention a person of ordinary skill in the art would have to engage in undue experimentation with no assurance of success.
Response to Arguments
Applicant’s arguments, see pg. 4, filed 07/06/2026, with respect to claims 5-8 have been fully considered and are persuasive. The rejection of 05/14/2026 has been withdrawn.
Closest Prior Art
The prior art made of record and not relied upon is considered pertinent to the applicant’s disclosure.
Chauhan et al. “PRMT-mediated regulatory arginine methylation of RIPK3” Cell Death Discovery, Vol. 9:14, PMID: 36658119, published January 19, 2023. Discloses that RIPK3 was found to be a target of PRMT5-mediated symmetric arginine demethylation. A conserved arginine residue in RIPK3 (R486 in human, R415 in mouse) was identified as the evolutionary conserved target for PRMT5-mediated symmetric demethylation.
Morgan et al. “Roles of RIPK3 in necroptosis, cell signaling, and disease” Experimental Molecular Medicine, Vol. 54., pg. 1695-1704, PMID: 36224345; published October 2022.
Discloses that the receptor-interacting protein kinase-3 (RIPK3 or RIP3) is an essential protein in the programmed and regulated cell death pathway called necroptosis.
Geserick et al. “Absence of RIPK3 predicts necroptosis resistance in malignant melanoma” Vol. 6:e1884, PMID: 26355347; published September 10, 2015.
Discloses that loss of RIPK3 in melanoma and selective inhibition of the RIPK3/MLKL axis by Dabrafenib is critical to protect from necroptosis.
Yang et al., “A glimpse of necroptosis and diseases” Biomedicine & Pharmacotherapy, Vol. 156:113925, PMID: 36411617; Epub October 27, 2022.
Discloses that programmed cell death is mediated by RIPK1, RIPK3, and MLKL and the potential of targeting necroptosis as a therapeutic strategy for various diseases.
Derakhshankha et al., “Cell-penetrating peptides: a concise review with emphasis on biomedical applications” Vol. 108, pg. 1090-1096, PMID: 30372809; published December 2018.
Discloses the use of peptides (such as TAT) as novel carriers for intracellular cargo (such as therapeutic agents, proteins) delivery which can translocate across the cell membrane.
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. 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 GEORGE T LOUNTOS whose telephone number is (571)272-0502. The examiner can normally be reached Monday-Friday 8:00 am - 5:00 pm.
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/GEORGE THEMISTOCLIS LOUNTOS/ Examiner, Art Unit 1652
/ROBERT B MONDESI/ Supervisory Patent Examiner, Art Unit 1652
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