DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. The Amendment filed on November 25, 2025, has been received and entered. It is noted that applicant has filed certified English translation of the foreign priority documents.
Claim Disposition
3. Claims 1-21, 23 and 26 are cancelled. Claims 29-38 have been added. Claims 22, 24-25 and 27-38 are pending and are under examination.
Claim objection
4. Claims 22, 24-25 and 27-38 are objected to for the following informalities:
For clarity and precision of claim language it is suggested that claim 1 is amended to read, “….chromatography on the crude product [[on a product]] ….wherein the PEGylated interleukin 2 comprises a disubstituted…and wherein content of the disubstituted….”. The dependent claims hereto are also included.
For clarity it is suggested that claim 33 is amended to read, “the crude product” in lieu of “ a sample”. The dependent claims hereto are also included.
Appropriate correction is required.
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.
5. Claims 22, 24-25 and 27-38 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.
Claim 22 is indefinite for the recitation of three different PEGylated IL-2 because the permeable does not indicate that multiple PEGs are involved in the method or the content of each PEG and importance of the same (see claims 24-25 and 27-28 for example). Note also that dependent claim 30 recites that the PEG is step 1 is methoxy PEG which means monosubstituted, thus not clear when in the process arrived as disubstituted and trisubstituted. The dependent claims hereto are also included.
Claim 32 lacks clear antecedent basis for the recitation of a gel chromatography system.
Claim 33 lacks clear antecedent basis for the recitation of “equilibration buffer” and mixture of the PEGylated interleukin 2. The dependent claims hereto are also included.
Claim 36 is indefinite because they lack clear antecedent basis for the recitation of “loading one or two of the flow-through peak component and the elution component”.
Claim 36 also lacks clear antecedent basis for the recitation of “the washing buffer A1, elution buffer B2, buffer A1 and B1 because claim 22 from which it depends does not recite multiple buffers. The dependent claims hereto are also included.
Claim 11 is indefinite for the recitation of "i.e.” which means ‘for example’ pertaining to the elution buffer, as the phrase renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention or just some suggestions. See MPEP 2173.05(d)
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
6. This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
7. Claim(s) 22, 24-25 and 27-38 is/are rejected under 35 U.S.C. 103 as being unpatentable over Charych et al. (2017, of record in the application) in view of NEKTAR THERAPEUTICS (2014, of record in the application).
Charych et al. discloses that NKRT-214 is 6-PEG-IL-2. The method for preparing 2-PEG-IL2 comprises intravenously injecting NKRT-214 into mice, and then collecting the plasma; releasing PEG linked to IL2 by hydrolysis; capturing IL2 and PEG-IL2 by means of using antibodies; and separating active 2-PEG-IL2, 1-PEG-IL2, and free-IL2 from non-active >3-PEG-IL2 by means of using a strong cationic resin and separating 1-PEG-IL2 and free IL2 from > 2-PEG-IL2 by means of using a weak cationic resin (see pages 4-7 and FIG 2). It can be seen that the differences between claim 22 and the primary reference lie in (1) PEG is reacted with IL-2 to obtain a crude product in claim 22, whereas the primary reference, has 2-PEG-IL-2 obtained by degrading NKRT-214; and (2) the separation and purification means of claim 22 is different from that of the primary reference. On the basis of the above-mentioned distinguishing technical features, claim 22 actually solves the problem of providing different synthesis, separation and purification methods of 2-PEG-IL-2 (note the primary reference FID 2 provides a variety of PEG). With regard to the difference (1), the secondary reference discloses IL-2 being controlled to conjugate to one, two or three PEGs by means of selecting an appropriate PEG reagent, ratio of the PEG reagent to an IL-2 moiety, temperature, a pH condition, etc. (see description, paragraphs [0096] and [0284)-[0285]. Further the buffering solutions are within the skill of the of the art.
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to arrive at the claimed invention as a whole because the combined teaching of the references renders it obvious and the references are analogous art.
Therefore, it would have been readily conceivable to obtain 2-PEG-IL-2 by means of using a synthetic method instead of NKRT-214 degradation. With regard to difference (2), the secondary reference discloses also separating PEG conjugates of different molecular weights by means of gel chromatography, separating isomers of the same molecular weight by ion exchange chromatography, and purifying the conjugate by an affinity column of the binding moiety of the binding sequence (such as an antibody, see description, paragraphs [0085] and [0286]-[0289]). Therefore, the separation and purification steps comprising gel chromatography, affinity chromatography and ion exchange chromatography would have been readily arrived at. On the basis that the primary reference discloses using an antibody for affinity chromatographic purification, it would have been readily conceivable to use other IL-2 specific binding substances, such as a receptor, for affinity chromatography. Therefore, claim 22 does not involve an inventive step (PCT Article 33 (3)). Furthermore, the secondary reference discloses the molecular weight of PEG comprising the range of 5kDa-100kDa. IL-2 can be conjugated to a PEG reagent functionalized with a succinimino derivative (or other activated ester groups, see description, paragraphs [0100] and [0148]). The separation and purification conditions of 2-PEG-IL-2 would have been obtainable to a person skilled in the art according to conventional separation methods of gel chromatography, affinity chromatography and ion exchange chromatography combined with simple parameter adjustment experiments. Moreover, the primary reference discloses that the NKTR-214 derivatives that bind to an IL-2 receptor and has highest activating activity are 1-PEG-IL-2 and 2-PEG-IL-2 (see page 10); and disclose multiple PEGs (see FIG2) and would essentially get the same results/activity. On the basis, a person skilled in the art would have been motivated to prepare the PEGylated IL2 that uses 2-PEG-IL-2 as a main ingredient and a pharmaceutically acceptable carrier into a pharmaceutical composition for the treatment of IL2 mediated diseases. Therefore, claimed invention is rendered obvious.
Response to Arguments
8. Applicant’s comments have been considered in full. Withdrawn objections/rejections will not discussed herein as applicant’s comments are moot. Note that new 112 second paragraph rejections have been instituted based on amendments made to the claims. In addition, the 103 rejection of record remains. The applicant traverses the rejection and state that claim 22 has been amended to recite ‘disubstituted, trisubstituted and monosubstituted, however, the primary reference teaches this as seen in for example FIG 2. Thus, the rejection remains and applicants comments are not deemed persuasive.
Conclusion
9. No claims are presently allowable.
10. Applicant’s amendment necessitated the new/modified 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 extension fee 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 date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to HOPE A ROBINSON whose telephone number is (571) 272-0957. The examiner can normally be reached 9-5pm on Monday to Friday.
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/HOPE A ROBINSON/Primary Examiner, Art Unit 1652