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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.
Remarks
The amendments and remarks filed on 02/11/2026 have been entered and considered. The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action. The rejections and/or objections presented herein are the only rejections and/or objections currently outstanding. Any previously presented objections or rejections that are not presented in this Office Action are withdrawn.
Claims 1-22 are pending.
Claim 5 is amended.
Claims 21-22 are new.
Claims 6-20 are withdrawn.
Claims 1-5 and 21-22 have been examined on the merits.
Priority
This application, U.S. Application number 17/505561, claims for domestic priority under 35 U.S.C. 119(e) to the provisional application No. 63/093777 filed on 10/19/2020.
Although Applicant claims for the benefit of the prior-filed application under 35 U.S.C. 119(e), Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) as follows. The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed provisional application No. 63/093777 fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. Specifically, the prior-filed provisional application No. 63/093777 only supports the claimed polypeptide having the amino acid sequence set forth in SEQ ID NO: 1 in the claim 4. However, the claimed limitations of a polypeptide having the amino acid sequence set forth in SEQ ID NO: 13 or SEQ ID NO: 19, as recited in the claims 1-3, 5, and 21-22 were introduced to the instant application, not supported by the prior-filed provisional application No. 63/093777.
Therefore, the priority date of provisional application is granted to Claim 4, but not to Claims 1-3, 5, and 21-22, since the claim 4 is the only claim that limits the polypeptide to have the amino acid sequence set forth in SEQ ID NO: 1. The effective filing date 10/19/2021 of the instant Application will be used for prior art purposes for Claims 1-3, 5, and 21-22.
Withdrawal of Rejections
The rejection of claim 5 under 35 U.S.C. 112(b) in the previous office action is withdrawn due to the amendment to the claim filed on 02/11/2026.
The rejection of claims 1-5 under 35 U.S.C. 103 over Vora et al. in view of Barad
is withdrawn in favor of the rejection listed below.
Claim Rejections - 35 USC § 112(d), or 112, Fourth Paragraph
Claims 5 and 22 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. This rejection is maintained for claim 5 and applied to the new claim 22.
Claims 5 and 22 recite the limitation that the chitinase comprises one or more of N45D, D47N, and R61M amino acid substitution mutations in the sequence of SEQ ID NO: 1, whereas the base claims 1 and 21 upon which the claims 5 and 22 respectively depend define that the chitinase comprises a polypeptide having the sequence of SEQ ID NO: 1, which does not have any of the N45D, D47N, and R61M mutations. Given these substitution mutations are not present in the chitinase recited in the base claim 1 or 21, the scope of Claims 5 and 22 is broader than that of Claims 1 and 21, respectively.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 103
Claims 1-5 and 21-22 are rejected under 35 U.S.C. 103 as being unpatentable over Vora et al. (WO 2008/002548 A2, 2008, of record) in view of Barad et al. (bioRxiv, posted online on Sep. 8, 2019; doi: http://dx.doi.org/10.1101/762336, of record) and Boot et al. (J. BIO. CHEM., 2001, 276(9): 6770 – 6778, of record).
Vora et al. teach a recombinant human acidic mammalian chitinase, i.e. an AMCase variant (variant of a wild type AMCase), wherein the AMCase variant comprises a substitution(s) at a position(s) corresponding to one or more residues of N45, N47, and R61 of the reference amino acid sequence (SEQ ID NO. 4) of the wild-type AMCase, specifically including N45D, N47D, and/or R61M substitutions (page 2/lines 17-27, Claims 1-4); and wherein an AMCase variant consists of the amino acid sequence set forth in SEQ ID NO: 2 comprising three substitutions of N45D, N47D, and R61M (page 2/lines 17-18 and 25-27, page 4/lines 6-8, Claim 5, Fig. 5). Vora et al. further teach that the amino acid substitutions in the AMCase variant improves the stability when compared to the wild type AMCase, which allows more efficient production of the AMCase enzyme, and facilitates high-throughput AMCase-based screening assays for identifying agents in treating symptoms of asthma (Claim 2, page 2/lines 9-16, page 4/lines 15-16, Fig. 8).
The amino acid sequence alignment between SEQ ID NO. 2 of the AMCase variant taught by Vora et al. and SEQ ID NO: 1 recited in Claims 1, 4, and 21 shows 99.2% sequency identity (see the alignment attached below). Specifically, the sequence of SEQ ID NO. 2 taught by Vora et al. has mismatches/substitutions N45D, D47N, R61M, and A239T at positions of 45, 47, 61, and 239, when being compared to the sequence of SEQ ID NO:1 of the instant claims (see highlighted mismatches (substitutions) in the alignment attached below). It is noted that the N45D, D47N, and R61M substitutions in the sequence of SEQ ID NO. 2 taught by Vora et al. read on the N45D, D47N, and R61M substitutions recited in the instant claims 5 and 22.
Query Match 99.2%; Score 2581; Length 476;
Best Local Similarity 99.2%;
Matches 472; Conservative 2; Mismatches 2; Indels 0; Gaps 0;
Qy 1 MTKLILLTGLVLILNLQLGSAYQLTCYFTNWAQYRPGLGRFMPDNIDPCLCTHLIYAFAG 60
||||||||||||||||||||||||||||||||||||||||||||:|:|||||||||||||
Db 1 MTKLILLTGLVLILNLQLGSAYQLTCYFTNWAQYRPGLGRFMPDDINPCLCTHLIYAFAG 60
Qy 61 RQNNEITTIEWNDVTLYQAFNGLKNKNSQLKTLLAIGGWNFGTAPFTAMVSTPENRQTFI 120
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 MQNNEITTIEWNDVTLYQAFNGLKNKNSQLKTLLAIGGWNFGTAPFTAMVSTPENRQTFI 120
Qy 121 TSVIKFLRQYEFDGLDFDWEYPGSRGSPPQDKHLFTVLVQEMREAFEQEAKQINKPRLMV 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 TSVIKFLRQYEFDGLDFDWEYPGSRGSPPQDKHLFTVLVQEMREAFEQEAKQINKPRLMV 180
Qy 181 TAAVAAGISNIQSGYEIPQLSQYLDYIHVMTYDLHGSWEGYTGENSPLYKYPTDTGSNTY 240
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||| |
Db 181 TAAVAAGISNIQSGYEIPQLSQYLDYIHVMTYDLHGSWEGYTGENSPLYKYPTDTGSNAY 240
Qy 241 LNVDYVMNYWKDNGAPAEKLIVGFPTYGHNFILSNPSNTGIGAPTSGAGPAGPYAKESGI 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 LNVDYVMNYWKDNGAPAEKLIVGFPTYGHNFILSNPSNTGIGAPTSGAGPAGPYAKESGI 300
Qy 301 WAYYEICTFLKNGATQGWDAPQEVPYAYQGNVWVGYDNIKSFDIKAQWLKHNKFGGAMVW 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 WAYYEICTFLKNGATQGWDAPQEVPYAYQGNVWVGYDNIKSFDIKAQWLKHNKFGGAMVW 360
Qy 361 AIDLDDFTGTFCNQGKFPLISTLKKALGLQSASCTAPAQPIEPITAAPSGSGNGSGSSSS 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 AIDLDDFTGTFCNQGKFPLISTLKKALGLQSASCTAPAQPIEPITAAPSGSGNGSGSSSS 420
Qy 421 GGSSGGSGFCAVRANGLYPVANNRNAFWHCVNGVTYQQNCQAGLVFDTSCDCCNWA 476
||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 GGSSGGSGFCAVRANGLYPVANNRNAFWHCVNGVTYQQNCQAGLVFDTSCDCCNWA 476
Regarding Claims 5 and 22, the AMCase variant having the sequence of SEQ ID NO. 2 taught by Vora et al. differs from the claimed recombinant chitinase in that the AMCase variant of Vora et al. does not have a substitution at the position 239, specifically the amino acid alanine “A” is substituted with an amino acid threonine “T”, i.e. an A239T substitution. Regarding Claims 1, 4, and 21, Examiner notes that the amino acid sequence of SEQ ID NO: 1 of the claimed recombinant chitinase comprises a single A239T substitution (when being compared to the sequence of the wild type chitinase), as evidenced by the disclosure of the specification (para 0017) and the drawing of SEQ ID NO: 1 in the provisional application No. 63/093777. Vora et al. does not teach an AMCase variant comprising only a single A239T substitution (without N45D, D47N, and/or R61M substitutions), i.e. an AMCase variant comprising a polypeptide having the amino acid of SEQ ID NO: 1, as required by the claims 1, 4, and 21.
Barad et al. investigated improvement of the activity of an AMCase by engineering the AMCase, and they generated a library of recombinant AMCase mutants with a recombinant expression approach and further assayed enzymatic activities of recombinant AMCase mutants, wherein the AMCase is a mouse AMCase, i.e. mAMCase (the paragraph spanning pages 4 and 5, Fig. 1). Barad et al. found that an AMCase mutant having substitution A239T along with L364Q (A239T/L364Q) is one of the most active mutants, with a 5-fold improvement in enzymatic activity (page 5, lines 1-2). Barad et al. further teach that AMCases are conserved across mammals (page 3, para 3/line 7). Barad et al. further teach that amino acid mutations/polymorphisms of human AMCase are associated with asthma, and recombinant chitinase can be applied as a potential direct therapy agent to ameliorate inflammatory lung diseases/symptoms (page 4, para 3/lines 1-2; page 3/lines 2-4 from bottom); and that a trio of mutations in human AMCase, N45D, D47N, and R61M, for increasing specific activity change residues to the wild type identities of mouse AMCase (mAMCase) (i.e. the wild type mAMCase has the amino acids D, N, and M at the positions 45, 47, and 61) (see the sentence spanning pages 3 and 4). As such, the A239T mutant of mAMCase taught by Barad et al. inherently comprises the amino acids D, N, and M respectively at the positions 45, 47, and 61, which are equivalent to N45D, N47D, and R61M substitutions in the human AMCase variant (hAMCase) taught by Vora et al.
Boot et al. teach isolating, cloning, and identifying acidic mammalian chitinase enzymes from rodents/mouse and human (title, abstract). Boot et al. disclose the amino acid sequences of the mouse acidic mammalian chitinase (i.e. mAMCase) and the human acidic mammalian chitinase (i.e. hAMCase) (page 6772/Fig. 2, and page 6776/Fig. 8A). Boot et al. further compare the amino acid sequences between hAMCase and mAMCase (page 6776/Fig. 8B), which shows 82% identity and 86% similarity (page 6775, left col, para 1, last 3 lines). It is noted that the amino acid sequence alignment in Fig. 8B did not include the first 21 amino acids (signal peptide) of the AMCases (see the legend of Fig. 8 at the bottom of page 6777). Accordingly, the alanine amino acid at position 239 of SEQ ID. NO: 1 of the instant claims as well as SEQ ID NOs: 2 and 4 of Vora et al. corresponds to alanine amino acid at the position 218 of the alignment (Note: 239-21 = 218). As shown in the Fig. 8B, the amino acids surrounding the alanine “A” at position 218 are highly conserved between hAMCase and mAMCase. It is further noted that in the alignment of Fig. 8B the mAMCase has the amino acids D, N, and M respectively at the positions 34, 36, and 40 (corresponding to 45D, 47N, and 61M in full-length recombinant AMCase of the claim 5 and Vora et al.), which differ from the amino acids N, D, and R at the same positions in the hAMCase (corresponding to N45, D47, and R61 in full-length wild type human AMCase, hAMCase). As such, the alignment in Fig. 8B taught by Boot et al. is consistent with the teachings of Barad et al. described above, i.e. a trio of mutations in human AMCase (hAMCase), N45D, D47N, and R61M, change residues to the wild type identities of mouse AMCase (mAMCase).
It would have been obvious to modify the AMCase variant taught by Vora et al. by substituting alanine with threonine at position 239, thus obtaining an AMCase variant having A239T substitution, for improving its enzymatic activity and identifying an AMCase variant suitable for being used as a direct therapy agent for treatment or amelioration of inflammatory lung and asthma symptoms, because it had been known in the art that the A239T substitution of AMCase enhances its enzymatic activity, and AMCase variants with improved enzymatic activity is a potential direct therapy agent for ameliorating inflammatory lung/asthma symptoms, as supported by Barad et al. It is noted that the AMCase of Barad et al. is a mouse AMCase (i.e. mAMCase), which differs from the human AMCase of Vora et al. (i.e. hAMCase) in their amino acid sequences. However, it would have been obvious to one of ordinary skill in the art to try the A239T substitution for modifying the AMCase variant taught by Vora et al. for improving its enzymatic activity and identifying an AMCase variant suitable for the direct therapy, because AMCases are conserved across mammals; and amino acids including the alanine amino acid at position 239 and amino acids surrounding the position 239 are highly conserved between the mAMCase and hAMCase; and the A239T mAMCase mutant comprising 45D, 47N, and 61M (equivalent to N45D, N47D, and R61M substitutions in hAMCase variant of Vora et al.) have been demonstrated to enhance AMCase’s enzymatic activity, as supported by Vora et al., Boot et al., and Barad et al. Furthermore, there are a limited number of AMCases available in the prior art, including human AMCase (hAMCase), for being tried with A239T substitution. See MPEP 2143 I.E., the rationale “obvious to try” supports a conclusion of obviousness when there is a finite number of identified and predictable solutions in the prior art, and choosing from such a finite number of identified and predictable solutions would have a reasonable expectation of success. Thus, it would have been obvious to try modifying the human AMCase variant taught by Vora et al. by substituting alanine with threonine at position 239, by incorporating the teachings of Barad et al. about A239T in mouse AMCase, thus obtaining a human AMCase variant having A239T substitution for improving its enzymatic activity and identifying an AMCase variant suitable for being used as the direct therapy agent.
With regard to the limitations about comprising a single A239T substitution (in the sequence of SEQ ID NO: 1 of claims 1, 4, and 21) or a combination of A239T with other substitutions N45D, D47N, and/or R61M (in claims 5 and 22), Vora et al. teach the AMCase variant comprises single one or more substitutions. It would have been obvious to construct AMCase variants comprising a single substitution or various different combinations of substitutions known to improve the activity/stability of the AMCase (such as A239T, N45D, D47N, R61M, and L364Q taught by Vora et al. and/or Barad et al) for investigating how these substitutions improve enzymatic activity. It is an obvious design choice to construct AMCase variants comprising a single substitution (e.g. a single A239T) as well as AMCase variants comprising a combination of different substitutions (e.g. a combination of A239T N45D, D47N, and R61M), such that AMCase variant having a single substitution (e.g. A239T) can be used as a control for assessing effect of each substitution mutation on the enzyme activity, and AMCase variant having a combination of substitutions (e.g. A239T, N45D, D47N, and R61M) can be used for assessing whether the combination of N45D, D47N, and R61M with an additional substitution (e.g. A239T) can further enhance the enzyme activity of the AMCase variant of Vora et al. Thus, the recombinant chitinase having the amino acid of SEQ ID NO: 1 (with a single A239T substitution) as well as the recombinant chitinase comprising a combination of A239T, N45D, D47N, and R61M would have been obvious over the combined teachings of Vora et al., Barad et al., and Boot et al.
Regarding the claim 2 and 3, it is noted that the amino acid sequence of SEQ ID NO: 1 recited in the claims 1 and 4 comprises the amino acid sequences of SEQ ID NOs: 19 and 13 respectively recited in the claims 2 and 3, as evidenced by the sequence alignment in page 6 of Applicant’s response filed on 02/11/2026. Accordingly, the AMCase variant with a single A239T substitution (i.e. having the sequence of SEQ ID NO: 1), suggested by Vora et al., Boot et al. and Barad et al., inherently comprises a polypeptide having the amino acid sequences of SEQ ID NO: 13 and SEQ ID NO:19, thus meeting the limitation requirements in the claims 2 and 3. As such, the combined teachings of the cited prior art render the claims 2 and 3 to be obvious.
Regarding the new claims 21 and 22, Vora et al. teach that the AMCase variant consists of a polypeptide having the amino acid sequence set forth in SEQ ID NO: 2 (a obvious variant of SEQ ID NO: 1, as indicated above). Furthermore, it noted that the claims 21-22 use the term “comprising” to limit the claimed chitinase. As such, the scope of the claimed chitinase is not excluded from further containing other peptides even though the claims use the term “consisting of” to limit a polypeptide to have the sequence of SEA ID NO: 1, 13, or 19. Thus, the claimed subject matter of claims 21-22 is not distinct from that of claims 1-5. As such, the claims are also obvious over the cited prior art for the reasons indicated for the claims 1-5.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention.
Response to Arguments
Applicant's arguments about the rejection of the claim 5 under 35 U.S.C. 112(b) in the response filed on 02/11/2026 (page 5) have been fully considered but they are moot, because the rejection has been withdrawn as indicated above.
Applicant's arguments about the rejection of the claim 5 under 35 U.S.C. 112(d) in the response filed on 02/11/2026 (page 5) have been fully considered but they are not persuasive. It is noted that the amendment to the claim 5 filed on 02/11/2026 is not sufficient to overcome the 112(d) rejection, because the scope of the amended claim 5 is still broader than that of the claim 1 for the reasons indicated above (see pages 4-5 for details).
Applicant's arguments about the rejection of claims 1-5 under 35 U.S.C. 103 over Vora et al. in view of Barad et al. in the 02/11/2026 response (pages 5-7) have been fully considered but they are not persuasive. Examiner notes that although Vora et al. do not teach a A239T substitution mutation in human AMCase, the modification of the AMCase of Vora et al. by introducing the A239T mutation would have been obvious to one of ordinary skill in the art in view of the combined teachings of Vora et al., Barad et al., and Boot et al. for the reasons indicated above in the 103 rejection (see pages 5-11 for details). As indicated above, the recombinant acidic chitinase having the A239T mutation taught by Barad et al. is a mutant of mouse chitinase (mAMCase), whose entire amino acid sequence does not exactly match to that of the human chitinase (hAMCase) used for making the recombinant acidic chitinase of the instant claims and Vora et al. However, it would have been obvious to try the A239T substitution for modifying the human AMCase variant taught by Vora et al. by incorporating the teachings of Barad et al. about A239T in mouse AMCase, thus arriving at the claimed invention for the reasons indicated above (see pages 9-10 for details).
Overall, the conclusion of the obviousness of the claims 1-5 and 21-22 has been established for all the reasons indicated above.
Conclusion
No claim is in condition for allowance.
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Any inquiry concerning this communication or earlier communications from the examiner should be directed to Qing Xu, Ph.D., whose telephone number is (571) 272-3076. The examiner can normally be reached on Monday-Friday from 9:30 AM to 5:00 PM. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Manjunath N. Rao, can be reached at (571) 272-0939. Any inquiry of a general nature or relating to the status of this application or proceeding should be directed to the receptionist whose telephone number is (571) 272-1600.
/Qing Xu/
Patent Examiner
Art Unit 1656