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 .
Claim Status
Claims 1-11 and 13-22 are pending. Claim 12 was canceled; claim 22 was newly added; and claims 1, 3-6, 8-11, 13, and 18-20 were amended in the Reply filed 4/29/2026. Claims 18 and 20-21 are rejoined. Claims 1-11 and 13-22 are presently considered.
Examiner Unable to Telephonically Contact Attorney of Record
Examiner notes that an attempt was made to contact Xiaofei Xue on 5/15/2026 to propose amendments necessary to place the Application in form for allowance. However, no phone number is associated with the Customer No. 14889, and the number provided in the Reply filed 4/29/2026 (i.e., (503)616-4800)) was non-functional on 5/15/2026.
Election/Restrictions
Applicant’s election without traverse of Group I (original claims 1-17 and 19-21) in the reply filed on 11/26/2025 was previously acknowledged.
The amendments filed 4/29/2026 are understood to overcome the rejections of record, and therefore examination has been extended to all fusion proteins (e.g., claims 1-11, 13-14, 19, and 22), which have been deemed free of the prior art. Examination has been extended to additional non-elected species, namely polynucleotides.
In view of Applicant’s amendments and allowable subject matter, claims 18 and 20-21 are rejoined1. Per MPEP § 803.02, examination has now been extended to other non-elected products and methods of using such products reading upon claims 15-18 and 19-21. Although these products are allowable, the claims are not in form for allowance at this time because the claims do not conform to the requirements of 35 USC §112.
Claims 1-11 and 13-22 are presently considered.
Priority
The priority claim to CN2019104074469 (filed 5/16/2019) and PCT/CN2020/070234, filed 1/03/2020, are acknowledged. The certified translation of CN2019104074469 filed on 4/29/2026 is acknowledged.
Information Disclosure Statement
The IDS filed 4/29/2026 is acknowledged and presently considered.
Claim Interpretation
The applicable claim interpretation was placed on record in the prior action (see, e.g., Action mailed 1/29/2026 at pages 6-8), and those discussions are incorporated herein, but not repeated.
Claim Objection
Claim 19 is objected to because of the following informalities:
Amended claim 19 recites “comprising culture of the expression system” at lines 1-2, which is lacking an article. Amended claim 19 should be amended to read “comprising a culture of the expression system” to include the indefinite article.
Appropriate correction is required.
Claim Rejections Necessitated by Applicant Amendment
Claim Rejections - 35 USC § 112(b)
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.
Claims 17, 19, and 20-21 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 17 is a product claim but currently recites a method step (“or incorporates the exogenous polynucleotide according to claim 15 in the genome”), which renders the product claim indefinite because it is unclear when infringement would incur (i.e., it is unclear if infringement of the product would occur before, during, or after the step is performed) (see, e.g., MPEP § 2173.05(p)(II)). Accordingly, claim 17 is rejected as indefinite. This rejection could be overcome by amended claim 17 to remove the phrase “or incorporates the exogenous polynucleotide according to claim 15 in the genome”.
Claim 17 recites and refers to “the genome”. There is insufficient antecedent basis for this limitation in the claim. This rejection could be overcome by amended claim 17 to remove the phrase “or incorporates the exogenous polynucleotide according to claim 15 in the genome”.
Claims 19 and 20-21 depend directly or indirectly from the indefinite claim 17, and fail to rectify the indefiniteness of claim 17. Accordingly, these claims are rendered indefinite for the reasons applicable to claim 17.
Accordingly, claims 17, 19, and 20-21 are rejected as indefinite.
Claim Rejections - 35 USC § 112(a), Scope of Enablement
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.
Claim 20 is 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 metabolism-related diseases, does not reasonably provide enablement for the treatment of all possible diseases. 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.
The applicable legal standards for enablement are discussed at MPEP § 2164 and the specific legal standards relevant to determinations regarding the scope of enablement are set forth at MPEP § 2164.08. MPEP § 2164 identifies the following relevant factors for determining “undue” experimentation: (A) The breadth of the claims; (B) The nature of the invention; (C) The state of the prior art; (D) The level of one of ordinary skill; (E) The level of predictability in the art; (F) The amount of direction provided by the inventor; (G) The existence of working examples; and (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.” The factors which have led the Examiner to conclude that the specification fails to teach how to make and/or use the claimed invention without undue experimentation, are addressed in detail below.
The breadth of the claims and nature of the invention: Claim 20 is directed to a panacea method of treating all possible diseases by administration of a peptide-based compound, including alopecia, Alzheimer’s disease, Creutzfeldt-Jakob Disease, Amyotrophic Lateral Sclerosis, Fibrodysplasia Ossificans Progressiva, Rabies, Parkinson’s disease, schizophrenia, cystic fibrosis, Arachibutyrophobia. Anatidaephobia, etc., etc.
The amount of direction or guidance presented and the existence of working examples: The originally filed disclosure provides zero guidance or working examples of methods of treating any non-metabolic diseases, or diseases such as Alzheimer’s disease, Creutzfeldt-Jakob Disease, Amyotrophic Lateral Sclerosis, Fibrodysplasia Ossificans Progressiva, Rabies, Parkinson’s disease, schizophrenia, cystic fibrosis, Arachibutyrophobia. Anatidaephobia, chemotherapy-induced peripheral neuropathy (“CIPN”), etc., etc. Therefore, zero guidance or direction for what would constitute a “therapeutically effective amount” of any compound of record for the treatment of such diseases appears on record.
The state of prior art: The lack of guidance and working examples is pertinent because the prior art fails to teach any polypeptide therapeutic analogous to those presently claimed that is capable of meaningfully treating all such diseases currently encompassed by claim 20. For example, no teachings of record suggest that a “therapeutically effective amount” of any substance within the scope of claim 20 is capable of “treating” Alzheimer’s disease, Creutzfeldt-Jakob Disease, Amyotrophic Lateral Sclerosis, Fibrodysplasia Ossificans Progressiva, Rabies, Parkinson’s disease, schizophrenia, cystic fibrosis, Arachibutyrophobia. Anatidaephobia, etc., etc. These examples are not exhaustive. Accordingly, in the complete absence of any objective evidence showing effectiveness or the existence of a “therapeutically effective amount” of such compounds capable of meaningfully “treating” all possible diseases, or otherwise a disclosed molecular pathway and mechanism connecting all possible diseases to outcomes achievable by administering the claimed polypeptides, artisans would not find such claim scope to be reasonable or credible.
Relative skill of those in the art, and the predictability or unpredictability of the art: Although the relative skill in the art is high, the general predictability of the disease treatment arts is very low because whole organism medical treatments are subject to high variability based upon subject parameters (e.g., age, weight, gender, and state of health), route of administration, dosage, therapeutic windows, specific disease being treated, and the definition of “treatment” for specific diseases. As noted above, in the complete absence of any objective evidence showing effectiveness or the existence of a “therapeutically effective amount” of such compounds capable of meaningfully “treating” all known diseases, or otherwise a disclosed molecular pathway and mechanism connecting all known diseases to outcomes achievable by administering the claimed polypeptides, artisans would not find such claim scope to be reasonable or credible.
The quantity of experimentation required to practice the claimed invention based on the teachings of the specification. While methods of treating various types of metabolic diseases using polypeptides similar to those presently claimed were known in the art at the time of the invention (see, e.g., art recited in pertinent prior art section, below), it was not routine in the art to utilize such polypeptides to treat all possible diseases, such as Alzheimer’s disease, Creutzfeldt-Jakob Disease, Amyotrophic Lateral Sclerosis, Fibrodysplasia Ossificans Progressiva, Rabies, Parkinson’s disease, schizophrenia, cystic fibrosis, Arachibutyrophobia. Anatidaephobia, chemotherapy-induced peripheral neuropathy (“CIPN”), etc., etc. Accordingly, in the absence of (i) objective evidence, or otherwise (ii) a biochemical mechanism pertinent to all possible diseases within the scope of claim 20, including CINP, allodynia, Alzheimer’s disease, etc., etc., one of skill in the art would not reasonably conclude that meaningful treatment of all possible diseases could be meaningfully achieved commensurate in scope with the instant claims, as treating all possible diseases using polypeptides as claimed was unknown in the prior art, but similar polypeptides were not taught, known, or utilized for treatment of all possible diseases. Therefore, at the time of filing, an artisan would reasonably doubt that such activity was possible to achieve in the absence of credible and substantial guidance. No such credible and substantial guidance has been set forth on record. Accordingly, to practice the full scope of the instant invention, an artisan would be unduly burdened to actually experimentally test every possible diseases known for a “therapeutically effective amount” of the compounds presently claimed, or otherwise identify a novel molecular mechanism connecting all possible diseases.
Conclusion: Therefore, in view of the lack of guidance and working examples, high degree of unpredictability, and failure to address the concerns present in the art, an artisan would be unduly burdened with experimentation in order to practice the full scope of the instantly claimed invention.
Accordingly, claim 20 is rejected. Applicant is advised that this rejection could be resolved by amending claim 20 to include the limitation of claim 21, and then canceling claim 21.
Allowable Subject Matter
Claims 1-11, 13-16, and 22 are allowed.
To place the application in form for allowance in an After-Final, Applicant may either delete claims 17-21 or otherwise amend the claims as follows:
Amend claim 17 to remove the phrase “or incorporates the exogenous polynucleotide according to claim 15 in the genome”.
Amend claim 19 to recite “comprising a culture of the expression system”.
Amend claim 20 to recite “A method for treating a metabolism-related disease”.2
Cancel claim 21.
Applicant is advised that adding previously unexamined claims in an After-final may necessitate additional search and examination, thereby preventing the after-final consideration.
Pertinent Prior Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
US8188040 (cited in previous action) discloses SEQ ID NO: 47, which appears to share substantial sequence identity with the Fc-Linker-FGF21 portion of instant SEQ ID NO: 106.
US9458214B2 (cited in previous action) discloses a dual function fusion protein comprising a GLP-1 receptor agonist, a FGF21 receptor agonist, and an Fc domain, attached to each other via a GS linker, and having an orientation of N-terminus-GLP-1 receptor agonist-linker-Fc domain-linker-FGF21 receptor agonist-C-terminus (see, e.g., US’214 at title, abs, claim 1).
US9731031B2 (cited in previous action) discloses oxyntomodulin conjugated to an immunoglobulin fragment (see, e.g., US’031 at title, abs, claims).
US 11858975 (cited in previous action) discloses and claims highly similar, but distinct species that are presently excluded from the pending claim scope (see, e.g., US’031 at title, abs, claims).
US20070237768A1 (cited in previous action) discloses FGF-21 compounds fused to specific IgG4-Fc or HSA derivatives resulting in fusion proteins that are biologically active with an extended elimination half-life and a slower clearance, and these FGF-21 compound fusion proteins and compositions are useful in treating type 2 diabetes, obesity, and metabolic syndrome (see, e.g., US’768 at title, abs, claims, passim).
US20140128318A1 (cited in previous action) discloses and claims novel oxyntomodulin derivatives and pharmaceutical composition for treating obesity comprising the same (see, e.g., US’318 at title, abs, claims).
US20150299282A1 (cited in previous action) discloses and claims a composition for preventing or treating diabetes, diabesity or diabetic complications, the composition comprising an oxyntomodulin analog as an active ingredient, wherein it is linked in a conjugate form to a half-life extending moiety (see, e.g., US’282 at title, abs, claims).
US20180311315A1 (cited in previous action) pertains to long-acting conjugates of GLP-1 agonists, and discloses conjugates of form X-La-F, wherein X is a peptide having activities to a glucagon receptor, L is a linker, and F is a material capable of increasing the half-life of X (see, e.g., US’315 at title, abs, claims, passim).
US20180305428A1 (cited in previous action) discloses long-acting fgf21 fusion proteins and pharmaceutical compositions comprising same (see, e.g., US’428 at title, abs, claims, passim).
WO2018081375A1 (cited in previous action) discloses Immunoglobulins and uses thereof, and generally teaches oxyntomodulin and other proteins conjugated to an Fc to increase half-life (see, e.g., id. at title, abs, claims, passim).
Pocai3 discusses the relationship and applications of both FGF21 and oxyntomodulin (see, e.g., id. at title, abs, passim).
Strohl4 discusses fusion proteins and strategies known in the art, circa 2015, for extending the half-life of protein therapeutics (see, e.g., id. at title, abs, passim).
Tschöp et al.5, discusses the trend towards unimolecular polypharmacy for treatment of diabetes and obesity, which is the process of taking different relative positions from various GLP-1 agonists and other similar proteins, and substituting those into a peptide to create a single molecule with dual activities (see, e.g., id. at title, abs, passim).
Yu et al.6 generally discusses fusion protein design, including multidomain fusion proteins, and the general state of the art circa 2014 (see, e.g., id. at title, abs, passim).
US20170183383A1 (June 29, 2017; cited in previous action) teaches and discloses analogues useful for preparing medication for treating hyperphagia, obesity and diabetes (see, e.g., US’383 at title, abs, claims). US’383 teaches and informs artisans that analogues include all species within the genus shown at claim 1 (see, e.g., US’383 at claim 1; see also US’383 at ¶¶[0010]-[0042], [0074]). US’383 recites structures of form
HX2QGTFTSDX10SKX13LDX16X17X18AX20X21FX23X24WLX27X28X29X30X31X32X33X34X35X36X37X38X39X40
(see, e.g., US’383 at claim 1, see also US’383 at ¶¶[0010]-[0042], [0074]). US’383 reads upon proteins comprising
HSQGTFTSDYSKYLDS[K or R]AAQDFVQWL[L or M][D,A,DA, or DT][GG or G]PSSGAPPPS
US’383 explicitly teaches that such compounds may be utilized in pharmaceutical compositions (see, e.g., US’383 at claims 8-11).
Conclusion
Claims 1-11, 13-16, and 22 are in form for allowance.
Claims 17-21 are rejected.
Applicant's amendment necessitated the new 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 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 RANDALL L BEANE whose telephone number is (571)270-3457. The examiner can normally be reached Mon.-Fri., 7 AM to 2 PM ET.
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, Lianko G. Garyu can be reached at (571) 270-7367. 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.
/RANDALL L BEANE/Primary Examiner, Art Unit 1654
1 Per MPEP 706.07(a), “if rejoinder occurs after a first Office action on the merits and if any of the rejoined claims are unpatentable (e.g., a rejection under 35 U.S.C. 112(a) is made), the next Office action may be made final if the rejection of the rejoined claims was necessitated by applicant’s amendment”.
2 Examiner notes that metabolism-related disease is defined at [0096].
3 Pocai, Action and therapeutic potential of oxyntomodulin. Mol Metab. 2013 Dec 14;3(3):241-51. doi: 10.1016/j.molmet.2013.12.001. PMID: 24749050; PMCID: PMC3986661; hereafter “Pocai” ; cited in previous action.
4 Strohl, W.R. Fusion Proteins for Half-Life Extension of Biologics as a Strategy to Make Biobetters. BioDrugs 29, 215–239 (2015). https://doi.org/10.1007/s40259-015-0133-6; hereafter “Strohl” ; cited in previous action.
5 Tschöp et al, Unimolecular Polypharmacy for Treatment of Diabetes and Obesity. Cell Metab. 2016 Jul 12;24(1):51-62. doi: 10.1016/j.cmet.2016.06.021. PMID: 27411008; hereafter “Tschop” ; cited in previous action.
6 Yu et al., Synthetic fusion protein design and applications. Biotechnol Adv. 2015 Jan-Feb;33(1):155-164. doi: 10.1016/j.biotechadv.2014.11.005. Epub 2014 Nov 18. PMID: 25450191; hereafter “Yu”; cited in previous action.
Prosecution Insights