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 6/25/2026 have been entered.
Claims 1-4, 7, 34 and 35 have been amended.
Claims 53-55 are new.
Claims 5, 6 and 8 have been cancelled.
In view of Applicants limiting the claimed invention to a transgenic mouse the scope of enablement rejection is withdrawn.
The 102 and 103 rejections have been amended to address new claims 53-55.
Claims 1-4, 7, 34, 35 and 53-55 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, 2, 4, 7 and 34 remain rejected and new claim 53 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Goldsmith et al. (WO 2000/39316, published 7/6/2000) for reasons of record in the Non-Final Office Action mailed 3/26/2026 (and repeated below as amended).
Regarding claim 1, Goldsmith et al. teach a transgenic mouse whose genome comprises a nucleic acid sequence encoding human CCR8 (see claims 1-3 and pg. 9 lines 19 bridge pg. 20 line 13).
Regarding claim 2, Goldsmith teaches human CCR8 is operably linked to an endogenous regulatory element at the endogenous CCR8 locus (pg. 10 lines 4-23).
Regarding claim 4, Goldsmith teaches that the sequence encoding human CCR8 is operably linked to an endogenous 5’ UTR (pg. 12 line 27 bridge pg. 13 line 6).
Regarding claim 7, Goldsmith teaches that their mouse does not express endogenous CCR8 (pg. 10 line 25 bridge pg. 12 line 5).
Regarding claim 53, Goldsmith teaches that one or more cells of their transgenic mouse will express human CCR8 (pg. 20 line 30 bridge pg. 21 line 8).
Regarding claim 34, Goldsmith teaches that their transgenic mouse can comprise an additional nucleic acid sequence encoding a human protein (pg. 19 lines 1-11).
Thus the teachings of Goldsmith clearly anticipate the invention of claims 1, 2, 4, 7, 34 and 53.
Response to Arguments
Applicant argues that Goldsmith does not produce any transgenic mice expressing human CCR8 and in view of MPEP 2121.01 an undue amount of experimentation would be required to practice the teachings of Goldsmith 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 CCR8. 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 Goldsmith is unpredictable for producing a transgenic mouse that expresses human CCR8. The claimed mouse only requires a nucleotide sequence encoding a human or chimeric CCR8 and that the mouse expresses a human or chimeric CCR8. In this regard, Goldsmith explicitly teaches that a transgenic mouse can express and secrete a chemokine receptor such as CCR8 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 provides no specific examples or arguments that expressing human CCR8 in a transgenic mouse is unpredictable or that the teachings of Goldsmith are unpredictable to practice the claimed invention.
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.
Claim(s) 1 and 3 remain rejected and new claims 53-55 are rejected under 35 U.S.C. 103 as being unpatentable over Goldsmith et al. (WO 2000/39316, published 7/6/2000) in view of Zaballos et al. (1996, Biochemical and Biophysical Res. Comm., Vol. 227, pgs. 846-853) reasons of record in the Non-Final Office Action mailed 3/26/2026 (and repeated below as amended).
Regarding claim 1, Goldsmith et al. teach a transgenic mouse whose genome comprises a nucleic acid sequence encoding human CCR8 (see claims 1-3 and pg. 9 lines 19 bridge pg. 20 line 13).
Regarding claim 53, Goldsmith teaches that one or more cells of their transgenic mouse will express human CCR8 (pg. 20 line 30 bridge pg. 21 line 8).
Goldsmith does not teach:
that the amino sequence is at least 70% or at least 90% identical to SEQ ID NO: 2.
Regarding the amino acid sequence for human CCR8 and claims 54 and 55,
Zaballos et al. teach the identification, characterization of functional domains and
full-length human amino acid sequence for CCR8 which is 100% identical to SEQ ID NO: 2.
It should be noted that Zaballos uses the term CKR-1, however it is known in the art that CKR-1 and CCR8 refer to the same protein.
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Thus at the time of filing the ordinary artisan would have found it prima facie obvious to combine the teachings of Goldsmith regarding a transgenic mouse which expresses human proteins such as CCR8 with the teachings of Zaballos regarding the amino acid sequence for human CCR8 to arrive at the claimed invention.
One of ordinary skill in the art would have been motivated to make such a combination since the amino acid sequence for human CCR8 was known and characterized at the time of filing.
There would have been a reasonable expectation of success that the transgenic mouse of Goldsmith could express a human CCR8 protein with 100% identity to SEQ ID NO: 2, since it was routine in the art to produce the nucleic acid sequence from the amino acid sequence.
Thus the cite art provides the requisite teachings and motivations to make and use the invention as claimed.
Response to Arguments
Applicants argue that there would have been no reasonable expectation of success to make the claimed CCR8-expressing mouse in view of the cited art. Applicants argue that Goldsmith teaches preparing rat lines carrying human CCR5 and that CCR8 only has a 40.8% alignment with CCR5 and thus a POSITA would not have concluded that expression of a CCR5 in transgenic mice indicates that CCR8 can be also be expressed in similar methods. While Applicant’s arguments have been fully considered they are not found persuasive.
The alignment of CCR5 to CCR8 is not persuasive regarding the pending obviousness rejection or that there would not be a reasonable expectation of success to express human CCR8 in a transgenic mouse. Goldsmith explicitly teaches that human CCR8 can expressed in their transgenic mouse and Zaballaos teaches a sequence which is 100% identical to SEQ ID NO: 2, thus the ordinary artisan is taught at the time of filing all of the necessary limitations to practice the claimed invention. A POSITA would have a reasonable expectation of success because Goldsmith teaches that human CCR8 can be expressed in a transgenic mouse.
Thus for the reasons above and of record the rejection is maintained.
Claim(s) 1, 34 and 35 remain rejected under 35 U.S.C. 103 as being unpatentable over Goldsmith et al. (WO 2000/39316, published 7/6/2000) in view of Rauch et al. (2019, Blood, Vol. 134(17), pgs. 1406-1414) and further evidenced by the teachings of Harper et al. (1991, J. Immunology, Vol. 147, pgs. 1037-1044) for reasons of record in the Non-Final Office Action mailed 3/26/2026 (and repeated below as amended).
Regarding claim 1, Goldsmith et al. teach a transgenic mouse whose genome comprises a nucleic acid sequence encoding human CCR8 (see claims 1-3 and pg. 9 lines 19 bridge pg. 20 line 13).
Regarding claim 34, Goldsmith teaches that their transgenic mouse can comprise an additional nucleic acid sequence encoding a human protein (pg. 19 lines 1-11).
Goldsmith does not teach:
that the additional nucleic acid is human CTLA-4.
Regarding an additional nucleic acid encoding human CTLA-4, Rauch et al.
teach the relationship between CCR8 and other proteins such as CTLA-4, PD-1, CD27, OX40 and LAG-3, commonly associated with tumor-associated Tregs in response to anti-PD1 treatment (see Abstract, pg. 1406 col. 2 parag. 2 and Fig. 3). Specifically, Rauch teaches that proteins such as CCR8 and CTLA-4 are related checkpoints when assaying cells in response to anti-cancer treatment (see Fig. 3 and 4).
Rauch concludes by teaching that their “data reveal a previously unappreciated origin of ATLL cells, confirm the report of rapid expansion of ATLL after PD-1 blockade in these patients, identify a novel connection between ATLL cells and tumor-resident Tregs, and expose an unresolved suppressive role for PD-1 in ATLL. Development of a model system that faithfully recapitulates these aspects of ATLL will be essential for establishing the mechanism underlying these findings and whether this is more broadly informative to the alarming problem of rapid progression of malignancy after immune checkpoint therapy.” (pg. 1412 col. 2 parag. 2 lines -10).
Further at the time of filing it was taught and known in the prior art regarding the nucleic acid sequence encoding human CTLA-4 as evidenced by the teachings of Harper et al.
Thus at the time of filing the ordinary artisan would have found it prima facie obvious to combine the teachings of Goldsmith regarding a transgenic mouse which expresses human proteins such as CCR8 with the teachings of Rauch regarding the relationship of human proteins such as CCR8 and CTLA-4 to arrive at the claimed invention.
One of ordinary skill in the art would have been motivated to make such a combination since Goldsmith teaches that their transgenic mice can comprise multiple human nucleic acid sequences encoding human proteins and Rauch teaching that proteins such as CTLA-4 and CCR8 can be used to evaluate treatment in response to anti-PD1 therapies. Thus a transgenic mouse expressing both human CCR8 and CTLA-4 would provide the ordinary artisan multiple checkpoints to evaluate anti-cancer therapies.
There would have been a reasonable expectation of success that the transgenic mouse of Goldsmith could express a second human proteins such as human CTLA-4 since the nucleotide sequence encoding human CTLA-4 was known at the time of filing and Goldsmith teaching that their transgenic mice can express multiple human proteins.
Thus the cite art provides the requisite teachings and motivations to make and use the invention as claimed.
Response to Arguments
Applicants argue that Rauch was merely cited to teach the relationship between CCR8 and other proteins such as CTLA-4, PD-1…and Harper was merely cited to teach the nucleic acid sequence encoding human CTLA-4. Applicants continue neither Rauch nor Harper can cure the deficiencies of Goldsmith. While Applicant’s arguments have been fully considered they are not found persuasive. Rausch teaches and motivates the ordinary artisan that CCR8 and other proteins such as CTLA-4 have a commonality in function/response and thus it would have been obvious to combine the teachings of Rausch with Goldsmith as set forth above.
Thus for the reasons above and of record the rejection is maintained.
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 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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