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 .
Applicants’ arguments and amendments filed on 6/17/2026 have been entered.
Claims 1-4, 20-22, 34 and 35 have been amended.
Claims 53-57 are new.
Claims 6, 8, 15, 17 and 23 have been cancelled.
In view of Applicant’s amendments the objections are withdrawn.
In view of Applicant’s amendments the scope of enablement is withdrawn.
In view of Applicant’s amendments, incorporating the limitation of a signal peptide from withdrawn claim 17 into claim 1, the 102 rejection is amended to cite the teachings of Ge et al. Further the 103 rejections of record have been amended in view of the new claims and amendments.
Claims 1-4, 20-22, 34, 35 and 53-57 are examined in the instant application.
Claim Rejections - 35 USC § 102
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 (i.e., changing from AIA to pre-AIA ) 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.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1-3, 20 and 22 remain rejected and new claims 53-57 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Gaitanaris et al. (WO 2004/040000 A2) and further evidenced by the teachings of Ge et al. (2014, Biosci. Rep., Vol. 34, pgs. 717-727) for reasons of record in the Non-Final Office Action mailed on 3/17/2026 (and repeated as amended below).
Regarding claims 1, 3, 20, 22, 53-57, Gaitanaris et al. teach a method of making a transgenic mouse whose genome comprises a human gene encoding GLP1R (SEQ ID NO: 459) which is 91.8% identical to instantly recited SEQ ID NO: 2 (see Abstract, pg. 318 lines 14-21, claim 452 and Fig. 1). Specifically, Gaitanaris teaches that their “invention features a transgenic mouse expressing a transgene encoding a human GPCR polypeptide listed in Table 1” (pg. 125 lines 25-26).
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Gaitanaris continues to teach a method of making a genetically-modified mouse using a mES cells that are inserted into a blastocyst and implanted into a female mouse as set forth in claim 20 (pg. 319 line 15 bridge pg. 320 line 3).
Regarding a GLP1R signal peptide, the teachings of Ge et al. are relied upon in teaching that GLP1R inherently comprises a signal peptide.
Gaitanaris teaches that one or more cells will express the human GLP1R (see Abstract and claim 440).
Regarding claim 2, Gaitanaris teaches that the human sequence encoding GLP1R is operably linked to an endogenous GLP1R locus (pg. 133 lines 10-16 and pg. 318 lines 14-21).
Thus Gaitanaris clearly anticipates the invention of claims 1-3, 20 and 22.
Response to Arguments
Applicant argues that Gaitanaris provides no experimental data regarding production of a transgenic mouse as claimed and in view of MPEP 2121.01 an undue amount of experimentation would be required to practice the teachings of Gaitanaris and thus is not enabling before the earliest effective filing date. Applicants further argue that amended claim 1 requires that the claimed transgenic mouse expresses the human or chimeric GLP1R. While Applicant’s arguments have been fully considered they are not found persuasive.
Applicants have not provided any evidence that at the time of filing the ordinary artisan would find the teachings of Gaitanaris is unpredictable for producing a transgenic mouse that expresses human GLP1R. The claimed mouse only requires a nucleotide sequence encoding a human or chimeric GLP1R and that the mouse expresses a human or chimeric GLP1R. In this regard, Gaitanaris explicitly teaches that a transgenic mouse can express and secrete a GLP1R as set forth in the amended claims. At the time of filing the art is replete with examples of transgenic mice successfully expressing human genes and Applicant has provided no specific examples or arguments that expressing human GLP1R in a transgenic mouse is unpredictable or that the teachings of Gaitanaris are unpredictable to practice the claimed invention.
Thus for the reasons above and of record the rejection is unpredictable.
Claim(s) 1, 4, 20 and 21 remain rejected under 35 U.S.C. 102(a)(1) as being anticipated by Jun et al. (2014, PLOS ONE, Vol. 9(4), pgs. 1-12) and further evidenced by the teachings of Ge et al. (2014, Biosci. Rep., Vol. 34, pgs. 717-727) for reasons of record in the Non-Final Office Action mailed on 3/17/2026 (and repeated as amended below).
Regarding claims 1 and 20, Jun et al. teach a method of making a humanized transgenic mouse expressing human GLP1-R (see Abstract).
Regarding a GLP1R signal peptide, the teachings of Ge et al. are relied upon in teaching that GLP1R inherently comprises a signal peptide.
Regarding claim 4, Jun teaches that the human GLP1-R is operably linked to the endogenous 5’UTR (pg. 2, col. 1 parag. 3).
Regarding claim 21, Jun teaches inserting Exons 1-13 of the human GLP1-R gene (Fig. 1A, reproduced below).
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Jun continues to teach a method of making a genetically-modified mouse using a mES cells that are inserted into a blastocyst and implanted into a female mouse as set forth in claim 20 (pg. 2 col. 1 last parag. bridge col. 2 parag. 2).
Jun teaches that the human GLP1R sequence is inserted within exon 1 of the mouse GLP1R locus (Fig. 1, figure legend).
Thus Jun clearly teaches the invention of claims 1, 4, 20 and 21.
Response to Arguments
Applicant argues that Jun does not teach a transgenic mouse that expresses a human or chimeric GLP1R and comprises a human GLP1R signal peptide. Applicant argues that Jun teaches using a mouse GLP1R signal peptide as set forth in Fig. 2B of Jun. While Applicant’s arguments have been fully considered they are not found persuasive.
Ge teaches that the signal peptide of GLP1R is not cleaved after receptor synthesis (pg. 725 col. 2 parag. 2) and thus remains present when GLP1R is synthesized. Based upon the teachings of Ge, this may be a unique feature to GLP1R as compared to other GPCR’s. In this regard the human GLP1R of Jun would thus still retain its signal peptide and meet the limitations of the claims.
Thus for the reasons above and of record the rejection is unpredictable.
Claim Rejections - 35 USC § 103
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 (i.e., changing from AIA to pre-AIA ) 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.
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.
Claim(s) 1, 34 and 35 remain rejected under 35 U.S.C. 103 as being unpatentable over Jun et al. (2014, PLOS ONE, Vol. 9(4), pgs. 1-12) in view of Viuff et al. (2016, J. Controlled Release, Vol. 223, pgs. 22-30) and evidenced by the teachings of White et al. (1986, Nucleic Acid Research, Vol. 14(12), pgs. 4719-4730) for reasons of record in the Non-Final Office Action mailed on 3/17/2026 (and repeated as amended below).
Regarding claim 1, Jun et al. teach a humanized transgenic mouse whose genome comprises a nucleic acid encoding human GLP1-R (see Abstract and Fig. 1).
Jun continues to teach that GLP-1 potentiates several therapeutic effects which are mediated by its receptor GLP1-R (pg. 1 cols. 1 and 2).
Jun concludes by teaching “Although much is now known about the role of GLP-1 in
controlling glucose metabolism, improving our understanding of the molecular mechanisms that regulate GLP-1R function in β cells and other tissues may enable development of improved GLP-1R-based therapies. An emerging area in GPCR biology is identifying partner or accessory proteins and understanding how GPCR interacting proteins help control signaling.” (pg. 11 col. 1 parag. 2 lines 1-7).
Jun does not teach:
a transgenic mouse further comprising a sequence encoding an additional human protein.
Regarding using an additional protein, Viuff et al. teach the benefits of generating
a double transgenic humanized mouse for studying the interaction between a ligand (albumin) and its receptor (neonatal Fc) (see Abstract and Introduction).Viuff continues to teach that “This work introduces a novel double transgenic humanized FcRn/ albumin mouse that maintains an autologous receptor/ligand interactionrequired for studying HSA-based drugs. The model was used successfully to discriminate PK profiles from albumins with different FcRn affinities in the presence of an endogenous pool of HSA. The model better mimics the human physiological conditions and, thus, has potential wide applications in the development of albumin-linked drugs or conventional drugs whose action is influenced by reversible binding to endogenous HSA.” (pg. 29 col. 1 parag. 3 bridge col. 2 lines 1-3).
Further, at the time of filing the nucleic acid sequence encoding human GLP1 was
known at the time of filing as evidenced by the teachings of White et al.
Thus at the time of filing the ordinary artisan would have found it prima facie obvious to modify the teachings of Jun regarding a humanized transgenic mouse whose genome comprises a nucleic acid encoding human GLP1-R with the teachings of Viuff regarding creating double transgenic mice that express a ligand and the corresponding receptor to arrive at the claimed invention.
One of ordinary skill in the art would have been motivated to make such a modification since Viuff teaches the advantages of generating double transgenic mice that express a ligand its receptor for the study of drug function and Jun teaching that GLP1-R is the receptor for GLP1.
There would have been a reasonable expectation of success that the humanized transgenic mouse, expressing human GLP1-R could further comprise and express human GLP1 since the nucleotide sequence encoding human GLP1 was known at the time of filing and Viuff teaching the successful creation of double transgenic mice.
Thus the cited art provides the requisite teachings and motivations to make and use the invention as claimed.
Response to Arguments
Applicant argues that Viuff was merely cited to teach the benefits of generating a double transgenic humanized mouse. Applicant continues that Huang et al. (Exhibit A) and Ge et al. (Exhibit B) teach opposite teachings regarding the necessity of a GLP1R signal peptide and that a POSITA would have no reasonable expectation of success to combine rely upon the art of record to practice the claimed invention. While Applicant’s arguments have been fully considered they are not found persuasive.
As set forth, Ge teaches that the signal peptide of GLP1R is not cleaved after receptor synthesis (pg. 725 col. 2 parag. 2) and thus remains present when GLP1R is synthesized. Based upon the teachings of Ge, this may be a unique feature to GLP1R as compared to other GPCR’s. In this regard the human GLP1R of Jun would thus still retain its signal peptide and meet the limitations of the claims. Thus, while Huang may teach the necessity of the signal peptide, Ge teaches that this signal peptide in GLP1R does remain post synthesis and these two teachings would be in agreement. Accordingly, a reasonable expectation of success would remain for practicing the claimed invention.
Thus for the reasons above and of record the rejection is unpredictable.
Conclusion
No claims are allowed.
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 DAVID A MONTANARI whose telephone number is (571)272-3108. The examiner can normally be reached M-Tr 8-6.
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DAVID A. MONTANARI
Examiner
Art Unit 1632
/ANOOP K SINGH/Primary Examiner, Art Unit 1632
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