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 .
DETAILED ACTION
1. Preliminary amendment and claims 1-18 filed on 3/13/24 are present and under consideration in this Office Action.
2. Priority
Receipt is acknowledged of papers (foreign priority filed 9/13/21) submitted under 35 U.S.C. 119(a)-(d), which papers have been placed of record in the file.
3. Specification
The specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant's cooperation is requested in correcting any errors of which applicant may become aware in the specification.
4. IDS(s) filed 6/13/24 & 4/28/25 are acknowledged. Signed copies of the IDS(s) are provided with this Office Action.
5. 35 U.S.C. § 112, first paragraph (Written Description)
Claims 1-18 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.
Claims 1-18 are directed to: A lipase mutant, wherein the lipase mutant comprises: 1) a protein having the amino acid sequence of SEQ ID NO: 1 with a mutation of one or more amino acids selected from the group consisting of: A262H, A338V, V364I, A158P, A158N, and I159N among other multiple mutants, with any level or % of sequence identity to the sequence of SEQ ID NO: 1; or in part 2 of claim 1 for example, a protein has the mutation of the protein in 1) and has an amino acid sequence with more than 80% identity to the amino acid sequence of the protein in 1), and the lipase mutant is derived from Pseudomonas putida and has the lipase activity. Similarly, claims 2-18 (protein, DNA, plasmid, host cell and method for preparing a chiral compound) and also with respect to part 1 of the claims, have any level or % of sequence identity to the sequence of SEQ ID NO: 1, as no level or % of sequence identity is claimed, the claimed genus.
In University of California v. Eli Lilly & Co., 43 USPQ2d 1938, the Court of Appeals for the Federal Circuit has held that “A written description of an invention involving a chemical genus, like a description of a chemical species, ‘requires a precise definition, such as by structure, formula, [or] chemical name,’ of the claimed subject matter sufficient to distinguish it from other materials”. As indicated in MPEP § 2163, the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show that Applicant was in possession of the claimed genus. In addition, MPEP § 2163 states that a representative number of species means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.
The specification, however, only provides description of six specific positional modifications at A262H, A338V, V364I, A158P, A158N, and I159N or multiple mutants using the six mutants in the instant specification and the sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO: 1. The specification does not contain any disclosure or description of the structure and function of all the lipase mutants having any level of sequence identity to SEQ ID NO: 1 or derivatives derived from such a sequence by insertion, deletion or substitution, and encoding a protein which has the enzymatic activity of a lipase; or the encoding DNA sequence(s). The 6 mutant species disclosed from Pseudomonas putida are not representative of the genus claimed. According to MPEP 2163, to satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v.Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed.Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116.
The scope of each genus includes many members of lipase enzymes with widely differing structural, chemical, and physical characteristics. Furthermore, each genus is highly variable because a significant number of structural differences between genus members exit. The specification does not describe and define any structural features and amino acid sequences commonly possessed by each genus. There is no art-recognized correlation between any structure of a lipase and sequences having varying sequence homology. Those of ordinary skill in the art would not be able to identify without further testing what specific DNA sequences would encode a protein having heparin synthase activity.
The genus of amino acid sequences that comprise these protein molecules may be obtained with the aid of a computer by a skilled artisan. However, there is no teaching regarding which 20% of the sequence (as in part 2 of the claim; or any % as in part 1) that can be varied and still result in a protein having lipase activity. An important consideration is that structure is not necessarily a reliable indicator of function. The instant specification provides no disclosure relating similarity or identity of structure to conservation of function. General knowledge in the art provides guidance to modification of some amino acids that are tolerated without losing a protein’s tertiary structure.
The claim includes a genus that can be analyzed at several levels sequentially for the purpose of focusing the issue. First, the disclosure of SEQ ID NO: 1 combined with pre-existing knowledge in the art regarding the genetic code and its redundancies would have put one in possession of the genus of proteins of SEQ ID NO: 1 (the encoding DNA). With the aid of a computer, one of skill in the art could identify all of the protein sequences with at least 80% sequence identity with SEQ ID NO: 1. However, there is no teaching regarding which 20% of the amino acids can vary from SEQ ID NO: 1 and still result in a protein that retains lipase activity. Further, there is no disclosed or art-recognized correlation between any structure other than SEQ ID NO: 1 and lipase activity. An important consideration is that structure is not necessarily a reliable indicator of function. In this example, there is no disclosure relating similarity of structure to conservation of function. General knowledge in the art included the knowledge that some amino acid variations are tolerated without losing a protein’s tertiary structure. The results of amino acid substitutions have been studied so extensively that amino acids are grouped in so-called “exchange groups” of similar properties because substituting within the exchange group is expected to conserve the overall structure. For example, the expectation from replacing leucine with isoleucine would be that the protein would likely retain its tertiary structure. On the other hand, when non-exchange group members are substituted, e.g., proline for tryptophan, the expectation would be that the substitution would not likely conserve the protein’s tertiary structure. Given what is known in the art about the likely outcome of substitutions on structure, those in the art would have likely expected the applicant to have been in possession of a genus of proteins having a tertiary structure similar to SEQ ID NO: 1 although the claim is not so limited. However, conservation of structure is not necessarily a surrogate for conservation of function. In this case, there is no disclosed correlation between structure and function. Accordingly, one of skill in the art would not accept the disclosure of SEQ ID NO: 1 (or the encoding DNA) as representative of other proteins having lipase activity. The specification, taken with the pre-existing knowledge in the art of amino acid substitution and the genetic code, fails to satisfy the written description requirement of 35 U.S.C. 112, first paragraph.
6. Claim Rejections - 35 USC § 112 (second paragraph)
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 1-18 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 pre-AIA the applicant regards as the invention.
Claims 1-5 recite – “lipase mutant is derived from Pseudomonas putida and has the lipase activity”. The claims are indefinite as no derivatives are taught. Substituting the word “obtained from” instead of ‘derived from’ is suggested to overcome this rejection.
Claims 6-18 are included in the rejection for failing to correct the defect present in the base claim(s).
7. 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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1 is/are rejected under 35 U.S.C. 102(a)(1)/(a)(2) as being anticipated by US-6551795-B1. US-6551795-B1 teaches a protein sequence with amino acid modification A158P – a natural mutant with respect to Applicants’ SEQ ID NO: 1 (part 1 of claim 1) and inherently possess lipase activity.
See the sequence alignment of Applicants’ SEQ ID NO: 1 and protein sequence of US-6551795-B1 presented below.
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844
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A158P – natural mutant
8. No claim is allowed.
9. Any inquiry concerning this communication or earlier communications from the examiner should be directed to TEKCHAND SAIDHA whose telephone number is (571)272-0940. The examiner can normally be reached on M-F 8.00-5.30. 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 B Mondesi can be reached on 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 an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/TEKCHAND SAIDHA/
Primary Examiner, Art Unit 1652
Recombinant Enzymes, Hoteling
Telephone: (571) 272-0940
Fax: (571) 273-0940