DETAILED ACTION
Status of Application
Claims 1-15, 26, 28, 38-40, 54, 66, and 81 are pending
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
A preliminary amendment of claims 1-11, 14, and cancellation of claims 16-25, 27, 29-37, 41-53, 55-65, 67-80, 82-94 as submitted in a communication filed on 06/18/2026 is acknowledged.
Applicant’s election without traverse of Group 1, claims 1-14, drawn to a drawn to a nucleic acid molecule encoding human adenosine deaminase 1 (HsADA1), wherein the HsADA1 has been mutated to have increased or prolonged stability or catalytic activity at physiological conditions relative to a wildtype HsADA1, as submitted in communication filed on 06/18/2026 is acknowledged.
Species Election, in the rely filed on 06/18/2026, was without traverse for the following species:
Genus A: mutations K164E, L194F, and Q202E.
Genus B: SEQ ID NO: 105.
Genus C: mutations Q175, E203, Q287, and K349.
Claims 15, 26, 28, 38-40, 54, 66, and 81 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 06/18/2026.
Claims 1-14 are at issue and are being examined only to the extent they encompass the elected invention.
Priority
Acknowledgment is made of applicant’s claim for domestic priority under 35
U.S.C. 119 (e) to provisional Application No. 63/278777 filed on 11/12/2021.
This is the US national application which entered the national stage from
Application No. PCT/US2022/079705 filed on 11/11/2022.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 05/09/2024 and 08/25/2025 are acknowledged. The submissions are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Drawings
The drawings submitted on 05/09/2024 have been reviewed and are accepted by
the examiner for examination purposes.
Claims Objections
Claim 1 is objected to due to the recitation of “nucleic acid molecule encoding human adenosine deaminase 1 (HsADA1) enzyme”. It should be amended to recite “nucleic acid molecule encoding a human adenosine deaminase 1 (HsADA1) enzyme”. Appropriate correction is required.
Claims 6-8 are objected to due to the recitation of “wherein the at least one mutation”. It should be amended to recite “wherein at least one mutation”. Appropriate correction is required.
Claim Rejections - 35 USC § 112(b) or Second Paragraph (pre-AIA )
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 1-14 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 1 (claims 2-14 dependent thereon) is indefinite in the recitation of “prolonged stability”, for the following reason: the term “prolonged” in claim 1 is a relative term which renders the claim indefinite. The term “prolonged” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Correction is required.
Claim Rejections - 35 USC § 112(a) or First Paragraph (pre-AIA )
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.
Claims 1-10 and 12-14. are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
As stated in MPEP 2111.01, during examination, the claims must be interpreted as broadly as their terms reasonably allow.
Claims 1-10 and 12-14 are directed in part to a polynucleotide encoding a HsADA1 (human adenosine deaminase 1) enzyme having any number of amino acid modifications resulting in the enzyme having an increased stability or catalytic activity.
Claims 3-10 are directed in part to a polynucleotide encoding a HsADA1 enzyme of SEQ ID NO:280 having one or more amino acid modifications recited in the claims and any other additional amino acid modifications resulting in said enzyme having increased stability or catalytic activity.
Therefore, the claims are directed to polynucleotides encoding a genus of HsADA1 mutants having the recited amino acid modifications and additional modifications, wherein the structure of the mutants is unknown, except for the recited amino acid modifications, and wherein the modifications result in increased stability or catalytic activity.
While the specification in the instant application discloses a limited number of nucleotide and amino acid sequences, it provides no clue as to the common structural elements that are representative of the full scope of the claimed genus. No disclosure of a structure/function correlation has been provided which would allow one of skill in the art to recognize which additional modifications would result in the increased stability or catalytic activity of HsADA1.
A sufficient written description of the genus of HsADA1 mutants having increased stability or catalytic activity may be achieved by a recitation of structural features common to members of the genus, which features constitute a substantial portion of the genus. However, in the instant case, there is no recited structural feature which is representative of all the members of the genus of HsADA1 mutants having an unknown structure, with exception of the recited amino acid changes, and having the property of having increased stability or catalytic activity, and there is no information as to which are the common structural elements of the HsADA1 mutants that are essential for the recited increase in stability or catalytic activity, or a correlation between structure and function which would provide those unknown structural features.
Furthermore, while one could argue that the few species disclosed are representative of the structure of all the members of the genus, it is noted that the art teaches several examples of how even highly structurally homologous polypeptides can have different enzymatic activities. For example, Witkowski et al. (Biochemistry 38:11643-11650, 1999) teach that one conservative amino acid substitution transforms a β-ketoacyl synthase into a malonyl decarboxylase and completely eliminates β-ketoacyl synthase activity. Tang et al. (Phil Trans R Soc B 368:20120318, 1-10, 2013) teach that two Dehalobacter reductive dehalogenases, CfrA and DcrA, having 95.2% sequence identity to teach other have exclusively different substrate (Abstract; page 7, left column, Discussion, CfrA and DcrA). Seffernick et al. (J. Bacteriol. 183(8):2405-2410, 2001) teach that two naturally occurring Pseudomonas enzymes having 98% amino acid sequence identity catalyze two different reactions: deamination and dehalogenation (Abstract), therefore having different function. Since minor structural differences may result in changes affecting function, and no additional information correlating structure with the desired functional characteristics has been provided, one cannot reasonably conclude that the few species disclosed are representative of the structure of all the HsADA1 mutants that are claimed. Therefore, one of ordinary skill in the art would not recognize from the disclosure that Applicant was in possession of the claimed invention.
Claims 1-10 and 12-14 are 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 nucleotide sequences: SEQ ID NOs: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77, 79, 81, 83, 85, 87, 89, 91, 93, 95, 97, 99, 101, 103, 105, 107, 109, 111, 113, 115, 117, 119, 121, 123, 125, 127, 129, 131, 133, 135, 137, 139, 141, 143, 145, 147, 149, 151, 153, 155, 157, 159, 161, 163, 165, 167, 169, 171, 173, 175, 179, 181, 183, 185, 187, 189, 191, 193, 195, 197, 199, 201, 203, 205, 207, 209, 211, 213, 215, 217, 219, 221, 223, 225, 227, 229, 231, 233, 235, 237, 239, 241, 283, and 285 that encode human adenosine deaminase 1 (HsADA1) enzymes with the amino acid sequences of SEQ ID NOs: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64, 66, 68, 70, 72, 74, 76, 78, 80, 82, 84, 86, 88, 90, 92, 94, 96, 98, 100, 102, 104, 106, 108, 110, 112, 114, 116, 118, 120, 122, 124, 126, 128, 130, 132, 134, 136, 138, 140, 142, 144, 146, 148, 150, 152, 154, 156, 158, 160, 162, 164, 166, 168, 170, 172, 174, 176, 178, 180, 182, 184, 186, 188, 190, 192, 194, 196, 198, 200, 202, 204, 206, 208, 210, 12, 214, 216, 218, 220, 222, 224, 226, 228, 230, 232, 234, 236, 238, 240, 242, 284, and 286, the specification does not reasonably provide enablement for a polynucleotide encoding HsADA1 mutants having an unknown structure, with the recited amino acid changes, and having increased stability or catalytic activity. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims.
Factors to be considered in determining whether undue experimentation is required are summarized in In re Wands (858 F.2d 731, 737, 8 USPQ2nd 1400 (Fed. Cir. 1988)) as follows: 1) quantity of experimentation necessary, 2) the amount of direction or guidance presented, 3) the presence and absence of working examples, 4) the nature of the invention, 5) the state of prior art, 6) the relative skill of those in the art, 7) the predictability or unpredictability of the art, and 8) the breadth of the claims. 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. Claims 1-10 and 12-14 broadly encompass a polynucleotide encoding HsADA1 mutants having an unknown structure, with the recited amino acid changes, and having increased stability or catalytic activity. The enablement provided is not commensurate in scope with the claims due to the lack of knowledge regarding the structure of the claimed HsADA1 mutants, with the recited amino acid changes. In the instant case, the specification enables nucleotide sequences: SEQ ID NOs: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77, 79, 81, 83, 85, 87, 89, 91, 93, 95, 97, 99, 101, 103, 105, 107, 109, 111, 113, 115, 117, 119, 121, 123, 125, 127, 129, 131, 133, 135, 137, 139, 141, 143, 145, 147, 149, 151, 153, 155, 157, 159, 161, 163, 165, 167, 169, 171, 173, 175, 179, 181, 183, 185, 187, 189, 191, 193, 195, 197, 199, 201, 203, 205, 207, 209, 211, 213, 215, 217, 219, 221, 223, 225, 227, 229, 231, 233, 235, 237, 239, 241, 283, and 285, and amino acid sequences: SEQ ID NOs: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, 50, 52, 54, 56, 58, 60, 62, 64, 66, 68, 70, 72, 74, 76, 78, 80, 82, 84, 86, 88, 90, 92, 94, 96, 98, 100, 102, 104, 106, 108, 110, 112, 114, 116, 118, 120, 122, 124, 126, 128, 130, 132, 134, 136, 138, 140, 142, 144, 146, 148, 150, 152, 154, 156, 158, 160, 162, 164, 166, 168, 170, 172, 174, 176, 178, 180, 182, 184, 186, 188, 190, 192, 194, 196, 198, 200, 202, 204, 206, 208, 210, 12, 214, 216, 218, 220, 222, 224, 226, 228, 230, 232, 234, 236, 238, 240, 242, 284, and 286.
The amount of direction or guidance presented and the existence of working examples. The specification discloses a limited amount of nucleotide and amino acid sequences. However, the specification fails to provide any clue as to the structural elements required in HsADA1 mutants having an unknown structure, with the recited amino acid changes, and having increased stability or catalytic activity. No correlation between structure and function has been presented.
The state of prior art, the relative skill of those in the art, and the predictability or unpredictability of the art. The structure of a protein determines its functional properties. While the art discloses a limited number of nucleotides and amino acid sequences, neither the specification nor the art provides a correlation between structure and function such that one of skill in the art can envision the structure of a HsADA1 mutant with any amino acid modification that can increase stability or catalytic activity. The art clearly teaches several examples of how even highly structurally homologous polypeptides can have different enzymatic activities. For example, Witkowski et al. (Biochemistry 38:11643-11650, 1999) teach that one conservative amino acid substitution transforms a β-ketoacyl synthase into a malonyl decarboxylase and completely eliminates β-ketoacyl synthase activity. Tang et al. (Phil Trans R Soc B 368:20120318, 1-10, 2013) teach that two Dehalobacter reductive dehalogenases, CfrA and DcrA, having 95.2% sequence identity to teach other have exclusively different substrate (Abstract; page 7, left column, Discussion, CfrA and DcrA). Seffernick et al. (J. Bacteriol. 183(8):2405-2410, 2001) teach that two naturally occurring Pseudomonas enzymes having 98% amino acid sequence identity catalyze two different reactions: deamination and dehalogenation, therefore having different function (Abstract).
The quantity of experimentation required to practice the claimed invention based on the teachings of the specification. While methods of correlating protein activity to modifications were known in the art at the time of the invention, it was not routine in the art to screen by a trial and error process for an essentially infinite number of HsADA1 mutants to find a HsADA1 mutant with the desired stability and activity. In the absence of (i) a rational and predictable scheme for selecting those mutants most likely to have the desired functional features, and (ii) a correlation between structure and the recited stability and activity, one of skill in the art would have to test an infinite number of mutants.
Therefore, taking into consideration the extremely broad scope of the claim, the lack of guidance, the amount of information provided, the lack of knowledge about a correlation between structure and the desired function, the high degree of unpredictability in the prior art regarding structural modifications and effects in function, one of ordinary skill in the art would have to go through the burden of undue experimentation in order to practice the claimed invention. Thus, Applicant has not provided sufficient guidance to enable one of ordinary skill in the art to make and use the invention in a manner reasonably correlated with the scope of the claims.
Claim Rejections - 35 USC § 102 (AIA )
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.
Claims 1 and 12-14 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Filpula et al. (US 20090047270 A1 published 02/19/2009; hereby “Filpula”).
Claims 1 and 12-14 as interpreted are directed in part to a nucleic acid molecule encoding human adenosine deaminase 1 (HsADA1) enzyme, wherein the HsADA1enzyme has been mutated to have increased or prolonged stability or catalytic activity at physiological conditions relative to a wildtype HsADA1 enzyme; a vector or expression cassette comprising said nucleic acid molecule; a cell comprising the vector or expression cassette; wherein the cell is a prokaryotic or a eukaryotic cell.
Filpula teaches bovine and human derivatives of ADA (Adenosine deaminase) enzymes including recombinantly produced ADA enzymes that have been mutated for enhanced stability relative to nonmutated recombinant ADA enzymes ([0058]). Filpula teaches the construction of an E. coli strain expressing recombinant human ADA ([0192]-[0193]). Therefore, the teachings of Filpula anticipate the instant claims as written/interpreted.
Claims 1-7, 10, and 12-14 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Sung et al. (KR 20090068644 A published 06/29/2009; hereby “Sung”). The examiner will use the English translation when referring to specific teachings relevant to the instant claims.
Claims 1-7, 10, 12-14 as interpreted are directed in part to a nucleic acid molecule encoding human adenosine deaminase 1 (HsADA1) enzyme, wherein the HsADA1 enzyme has been mutated to have increased or prolonged stability or catalytic activity at physiological conditions relative to a wildtype HsADA1 enzyme; wherein the nucleic acid molecule encoding the HsADA1enzyme has been mutated at one or more amino acid positions comprising a charged amino acid to a neutral or differently charged amino acid; wherein the nucleic acid molecule encodes an amino acid sequence comprising comprises at least one mutation in one or more of positions D8, S21, R33, N41, G45, V49, T57, G134, A148, N160, P163, K164, Q173, Q174, P189, L194, Q199, Q202, I261, I281, L283, and/or R341 of SEQ ID NO: 280; wherein at least one mutation in the amino acid sequence encoded by the nucleic acid molecule is in one or more of positions D8, S21, R33, N41, G45, V49, T57, G134, A148, N160, P163, K164, Q173, P189, L194, Q199, Q202, I261, I281, L283, and/or R341 of SEQ ID NO: 280; wherein at least one mutation in the amino acid sequence encoded by the nucleic acid molecule alters the charge of one or more of positions D8, S21, R33, N41, G45, V49, T57, G134, A148, N160, P163, K164, Q173, P189, L194, Q199, Q202, 1261, I281, L283, and/or R341 of SEQ ID NO: 280; wherein the at least one mutation in the amino acid sequence encoded by the nucleic acid molecule is selected from the group consisting of: N at position D8;A at position S21;K at position R33;D at position N41; E at position G45;I at position V49;S at position T57;N at position G134;V at position A148;S at position N160;S at position P163;E at position K164;N or E at position Q173;E at position Q174;E at position P189;F at position L194;K at position Q199;E at position Q202;V at position I261;V at position I281;F at position L283; and K at position R341; wherein the at least one mutation in the amino acid sequence encoded by the nucleic acid molecule comprises R33K, N41D, K164E,Q173N, L194F, Q199K, and/or Q202E; wherein the amino acid sequence encoded by the nucleic acid molecule further comprising comprises at least one additional mutation in one or more of positions 160-202 of SEQ ID NO: 280.
Claims 12-14 as interpreted are directed in part to a vector or expression cassette comprising the nucleic acid molecule of claim 1, a cell comprising the vector or expression cassette of claim 12; wherein the cell is a prokaryotic or an eukaryotic cell.
Sung teaches a variant of human adenosine deaminase with increased activity; wherein amino acid residue K164 of the human adenosine deaminase marked as sequence number 2 (seq id no: 2) is substituted for E (Claim 2, part ii). Sung teaches a variant represented by the amino acid sequence of seq id no: 2, wherein Y201 of human adenosine deaminase, is substituted with F (Claim 2, part iii). It is noted that sequence id no: 2 (Sequence on pages 17-19 of original patent) of Sung and SEQ ID NO: 280 of this instant case are 100% identical (see alignment below). Sung teaches that the mutant adenosine deaminase showed an increase in activity more than 2-fold of the wild-type adenosine deaminase at 37°C ([0057]-[0058]). Sung teaches the transformation and culture of E. coli, wherein expression vectors were inserted to encode the human adenosine deaminase ([0040]-[0042]).
Therefore, the teachings of Sung et al. anticipate the instant claims as written/interpreted.
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Claim Rejections - 35 USC § 103 (AIA )
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.
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.
Claims 1-7, 10, 12-14 are rejected under 35 U.S.C. 103 as being unpatentable over Filpula et al. (US 20090047270 A1 published 02/19/2009; hereby “Filpula”), in view of Sung et al. (KR20090068644A published 06/29/2009; Hereby “Sung”) (English translation provided).
Filpula teaches bovine and human derivatives of ADA (Adenosine deaminase) enzymes including recombinantly produced ADA enzymes that have been mutated for enhanced stability relative to nonmutated recombinant ADA enzymes ([0058]). It is noted that SEQ ID NO: 3 of Filpula is identical to the human ADA of SEQ ID NO:280 of this instant case, except by 1 amino acid, having a 99.2% sequence identity (see alignment below). Filpula teaches the construction of an E. coli strain expressing recombinant human ADA ([0192]-[0193]). Filpula teaches that the preferred condition to allow high level production of the ADA enzyme is 37°C ([0199]).
Filpula does not teach the nucleic acid molecule of claim 1, wherein the nucleic acid molecule encoding the HsADA1 enzyme has been mutated at one or more amino acid positions comprising a charged amino acid to a neutral or differently charged amino acid; wherein the nucleic acid molecule encodes an amino acid sequence comprising at least one claimed mutation in one or more of the claimed positions of SEQ ID NO: 280; wherein the amino acid sequence encoded by the nucleic acid molecule further comprises at least one additional mutation in one or more of positions 160-202 of SEQ ID NO: 280.
Sung teaches a variant of human adenosine deaminase with increased activity; wherein amino acid residue K164 of the human adenosine deaminase marked as sequence number 2 (seq id no: 2) is substituted for E (Claim 2, part ii). Sung teaches a variant represented by the amino acid sequence of seq id no: 2, wherein Y201 of human adenosine deaminase, is substituted with F (Claim 2, part iii). It is noted that sequence id no: 2 (Sequence on pages 17-19 of original patent) of Sung and SEQ ID NO: 280 of this instant case are 100% identical (see alignment below). Sung teaches that the mutant adenosine deaminase showed an increase in activity more than 2-fold of the wild-type adenosine deaminase at 37°C ([0057]-[0058]). Sung teaches the transformation and culture of E. coli, wherein expression vectors were inserted to encode the human adenosine deaminase ([0040]-[0042]).
It would have been obvious to one of ordinary skill in the art before the effective
filing date of the claimed invention to modify the human ADA taught by Filpula to incorporate the amino acid substitutions taught by Sung, including the substitutions at positions 164 and 201.
A person of ordinary skill in the art is motivated to modify to incorporate the recited substitutions because said substitutions increase enzyme activity as taught by sung. One of ordinary skill in the art would have reason to incorporate the substitutions of Sung to increase enzyme activity. One of ordinary skill in the art has a reasonable expectation of success because Sung teaches said substitutions in the same human adenosine deaminase sequence corresponding to SEQ ID NO: 280 in the instant application. 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.
Sequence 3, US/12105682
Patent No. 8741283
GENERAL INFORMATION
APPLICANT: FILPULA, David R.
APPLICANT: SAPRA, Puja
TITLE OF INVENTION: ENZYMATIC ANTICANCER THERAPY
FILE REFERENCE: 213.1261-U
CURRENT APPLICATION NUMBER: US/12/105,682
CURRENT FILING DATE: 2008-11-01
PRIOR APPLICATION NUMBER: US 60/913,039
PRIOR FILING DATE: 2007-04-20
NUMBER OF SEQ ID NOS: 5
SEQ ID NO 3
LENGTH: 362
TYPE: PRT
ORGANISM: Human
FEATURE:
NAME/KEY: misc_feature
LOCATION: (74)..(74)
OTHER INFORMATION: Cys to Ser mutein
Query Match 99.2%; Score 1889; Length 362;
Best Local Similarity 99.7%;
Matches 360; Conservative 0; Mismatches 1; Indels 0; Gaps 0;
Qy 2 AQTPAFDKPKVELHVHLDGSIKPETILYYGRRRGIALPANTAEGLLNVIGMDKPLTLPDF 61
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 AQTPAFDKPKVELHVHLDGSIKPETILYYGRRRGIALPANTAEGLLNVIGMDKPLTLPDF 60
Qy 62 LAKFDYYMPAIA GCREAIKRIAYEFVEMKAKEGVVYVEVRYSPHLLANSKVEPIPWNQAE 121
||||||||||||| ||||||||||||||||||||||||||||||||||||||||||||||
Db 61 LAKFDYYMPAIA GSREAIKRIAYEFVEMKAKEGVVYVEVRYSPHLLANSKVEPIPWNQAE 120
Qy 122 GDLTPDEVVALVGQGLQEGERDFGVKARSILCCMRHQPNWSPKVVELCKKYQQQTVVAID 181
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 GDLTPDEVVALVGQGLQEGERDFGVKARSILCCMRHQPNWSPKVVELCKKYQQQTVVAID 180
Qy 182 LAGDETIPGSSLLPGHVQAYQEAVKSGIHRTVHAGEVGSAEVVKEAVDILKTERLGHGYH 241
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 LAGDETIPGSSLLPGHVQAYQEAVKSGIHRTVHAGEVGSAEVVKEAVDILKTERLGHGYH 240
Qy 242 TLEDQALYNRLRQENMHFEICPWSSYLTGAWKPDTEHAVIRLKNDQANYSLNTDDPLIFK 301
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 TLEDQALYNRLRQENMHFEICPWSSYLTGAWKPDTEHAVIRLKNDQANYSLNTDDPLIFK 300
Qy 302 STLDTDYQMTKRDMGFTEEEFKRLNINAAKSSFLPEDEKRELLDLLYKAYGMPPSASAGQ 361
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 STLDTDYQMTKRDMGFTEEEFKRLNINAAKSSFLPEDEKRELLDLLYKAYGMPPSASAGQ 360
Qy 362 N 362
|
Db 361 N 361
Claim 9 is rejected under 35 U.S.C. 103 as being unpatentable over Filpula et al. (US 20090047270 A1 published 02/19/2009; hereby “Filpula”), in view of Sung et al. (KR20090068644A published 06/29/2009; Hereby “Sung”) (English translation provided), as applied to claims 1-7, 10, 12-14 above, in further view of Wang et al. (Toxicological Sciences 125.2 (2012): 509-521; hereby “Wang”).
The combined teachings of Filpula and Sung are discussed above. The combined teachings of Filpula and Sung do not teach mutating position 279 human ADA.
Wang teaches that A279 of human adenosine deaminase is a part of the binding site (Table 3).
It would have been obvious to one of ordinary skill in the art before the effective
filing date of the claimed invention to further mutate the human adenosine deaminase of the combined teachings of Filpula and Sung at amino acid position 279. A person of ordinary skill in the art is motivated to modify amino acid residue 279 because Wang identifies A279 as a binding site residue of human adenosine deaminase, thereby identifying A279 as a functionally relevant position for modification. One of ordinary skill in the art has a reasonable expectation of success because Filpula and Sung establish that the human adenosine deaminase is improved with amino acid substitutions, while Wang identifies 279 as a binding site residue, making residue 279 a target for modification. Accordingly, substitution of residue 279 would have been obvious to try as a predictable modification of a known residue involved in binding. 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.
Conclusion
No claim is in condition for allowance.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SYNPHANE SHELTON whose telephone number is (571)272-6318. The examiner can normally be reached 9:00am-7pm.
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, Robert Mondesi can be reached at (408) 918-7584. 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.
/S.L.S./Examiner, Art Unit 1652
/ROBERT B MONDESI/Supervisory Patent Examiner, Art Unit 1652
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