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 .
Remarks
The amendments and remarks filed on 10/16/2025 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 Any previously presented objections or rejections that are not presented in this Office Action are withdrawn. Claims 27-42 are pending; Claims 1-26 are cancelled; Claims 27-42 are new; Claims 41-42 are withdrawn as being drawn to a non-elected invention; and Claims 27-40 are under examination.
Withdrawal of Objections
The objection to Claim 23 is withdrawn due to the cancellation of the claim filed on 10/16/2025.
Withdrawal of Rejections
The rejection of Claims 16-24 under 35 U.S.C. 101, as the claim is directed to a judicial exception without significantly more, is withdrawn due to the cancellation of the claims filed on 10/16/2025.
The rejection of Claims 16-21 and 24 under 35 U.S.C. 112(a) as failing to comply with the written description requirement, is withdrawn due to the cancellation of the claims filed on 10/16/2025.
The rejection of Claims 16-24 under 35 U.S.C. 112(b) is withdrawn due to the cancellation of the claims filed on 10/16/2025.
The rejection of Claims 20-21 and 23 under 35 U.S.C. 102(d) is withdrawn due to the cancellation of the claims.
The rejection of Claims 16, 20-21, and 24 under 35 U.S.C. 103 over Lu-2 et al. in view of Niyonzima et al. and Gjermansen is withdrawn due to the due to the cancellation of the claims.
The rejection of Claim 23 is rejected under 35 U.S.C. 103 over Bergholz et al./Ayala-del-Río et al. in view of Niyonzima et al. and Gjermansen is withdrawn due to the due to the cancellation of the claims.
Specification
The specification is objected to because two sets of paragraphs 1-40 are recited in the specification. See PGPub US 2022/0411773 of the instant application: the first set of paragraphs 1-40 are disclosed in pages 1-3, and another distinct set of paragraphs 1-40 are recited throughout paragraphs [0456] and [0488] – [0529] in pages 30-33 of the PGPub. Applicant is required to make Appropriate correction without introducing new matter in response to this Office action. This objection is maintained.
Claim Rejections - 35 USC § 101
Claims 27-40 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (a natural phenomenon) without significantly more, as evidenced by De et al. [RSC Adv., 2015, Vol. 5, pages 1-27 (original page number is 65757-65767), of record], and Donio et al. (SpringerPlus 2013, 2:149, pages 1-10, of record).
The base claim 27 is directed to a composition which is one of four categories of patent eligible subject matter (Step 1: Yes).
The base claim 27 is directed to a composition comprising a surfactant and a polypeptide having proteolytic activity. The claimed surfactant and polypeptide are all naturally occurring substances produced by naturally occurring microbes, as evidenced by De et al. (abstract, page 11) and Donio et al. (title, abstract), who teach respectively that natural surfactants/biosurfactants are produced by various microbes including bacteria, yeast, and fungi, and that biosurfactant is produced by a naturally occurring halophilic bacterium; and as evidenced by the specification of the instant application, the claimed polypeptides are obtained from microorganisms of the nature (e.g. in soil or water) (see page 19, lines 12-16). It is noted that the claims do not recite any limitation to define concentrations or amounts of the polypeptide/protease and surfactant in the claimed composition, thus they can be at any amounts. There is no indication in the specification that any amounts of polypeptide/protease and surfactant present in the claimed composition has any characteristics (structural or functional) that are different from their naturally occurring counterparts in the natural state. Accordingly, the claim is directed to “products of nature” judicial exception (Step 2A, Prong 1: Yes).
The judicial exception in the claim 27 is not integrated into a practical application because the claim is directed to a product, not a method of use (Step 2A: Prong 2: No).
The claim 27 further recites the limitation to define the composition in the form of liquid, gel, powder, granulate, paste or spray. However, this limitation is at a high level of genericity and the claim appears to recite all the possible forms of the composition (i.e. liquid, solid, semi-liquid, and semi-solid). As such, the claim does not include additional elements that are sufficient to amount to significantly more than the judicial exception (Step 2B: No).
Dependent claims 28-36 and 38-39 further recite the limitations to limit the sequence identity of the clamed polypeptide to the SEQ ID Nos. 21, 3, 6, 9, 12, and/or 18, or describe the sequence of the clamed polypeptide. As indicated above, the specification discloses that the claimed polypeptides are obtained from microorganisms of the nature (e.g. soil, water). There is no indication in the specification that the polypeptide having proteolytic activity in the claimed composition has any characteristics (structural or functional) that are different from their naturally occurring counterparts. Therefore, the limitations recited in the claims are still directed to the “products of nature” judicial exception of the claim 27.
Dependent claim 37 further limits the clamed polypeptide to be a fragment of the polypeptide having the amino acid sequence of SEQ ID Nos. 21, 3, 6, 9, 12, or 18. It is noted that naturally occurring polypeptides having proteolytic activity are present in the form of fragments, because they are generated through naturally occurring events of protein degradation. There is no indication in the specification that the claimed polypeptide in the form of fragment has any characteristics (structural or functional) that are different from their naturally occurring counterparts. Therefore, the limitation recited in the claim is still directed to the “products of nature” judicial exception of the claim 27.
Dependent claim 40 further recites the limitation of “a builder”. However, this limitation is at a high level of genericity because the claim does not define any specific structure of the builder. The specification (page 31, lines 13-17) discloses the builder can be citric acid, citrates, carbonates, bicarbonates, zeolite, and/or silicates, which are all naturally occurring substances. Therefore, the limitation recited in the claim is still directed to the “products of nature” judicial exception of the claim 27.
Therefore, Claims 27-40 are deemed to be patent ineligible.
Claim Rejections - 35 USC § 112, First Paragraph
Claims 27-36 and 40 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(s), at the time the application was filed, had possession of the claimed invention.
The claims 27-36 and 40 are directed to a composition comprising a polypeptide having proteolytic activity, selected from the group consisting of polypeptides having sequence identities of at least 96%, 93%, 94%, 81%, 80%, and 80%, respectively, to SEQ ID NO: 21, 3, 6, 9, 12, 15 and 18. The claims 28-30 further limit the polypeptides to have the sequence identities of at least 97%, 94%, 95%, 85%, 85%, and 85%, respectively, to SEQ ID NO: 21, 3, 6, 9, 12, and 18; or at least 98%, 95%, 96%, 90%, 90%, and 90%, respectively, to SEQ ID NO: 21, 3, 6, 9, 12, and 18; or at least 99%, 97%, 98%, 95%, 95%, and 95%, respectively, to SEQ ID NO: 21, 3, 6, 9, 12, and 18. Examiner notes that the amino acid sequence lengths of SEQ ID NO: 21, 3, 6, 9, 12, and 18 are in a range from 346 amino acids (AAs) to 451 amino acids (AAs). The claimed lowest sequence identity is at least 80% to SEQ ID NO:12 (354 AAs) or SEQ ID NO: 18 (370 AAs), which would allow up to 71 or 74 amino acids throughout the entire sequence of SEQ ID NO:12 or 18 to be mutated by substitution, deletion, and/or insertion for generating the claimed polypeptide. The claimed highest sequence identity is at least 99% to SEQ ID NO:21 (375 AAs), which would allow up to 4 amino acids throughout the entire sequence of SEQ ID NO:21 to be mutated by substitution, deletion, and/or insertion, for generating the claimed polypeptide. As such, the amino acid number allowed to be mutated in the polypeptide sequences of SEQ ID NO: 21, 3, 6, 9, 12, or 18 is ranged from 4 amino acids to 74 amino acids, for generating the claimed polypeptides. Examiner further notes that the instant claims do not define any specific positions where the mutations occur, and the claims do not define any specific types of mutations occurring throughout the sequence of SEQ ID NO: 21, 3, 6, 9, 12, or 18. Accordingly, the claimed polypeptide may be derived from a polypeptide of SEQ ID NO: 21, 3, 6, 9, 12, or 18 by any types of mutations (substitution, deletion, and/or insertion of any amino acids) at any positions in the amino acid sequence ranged from 346 AAs to 451 AAs. As such, the scope of the polypeptides that meet the claimed sequence identity to SEQ ID NO: 21, 3, 6, 9, 12, or 18 encompasses extremely large number of different polypeptide variants or mutants derived from the polypeptide of SEQ ID NO: 21, 3, 6, 9, 12, and 18.
The specification provides no information about the structural - proteolytically functional relationship for the polypeptides having the sequence of SEQ ID NOs: 21, 3, 6, 9, 12, or 18 in a range of 346 AAs - 451 AAs. Given the claims do not recite actual structural limitations, an extremely large numbers of variants/mutants of the polypeptide of SEQ ID NOs: 21, 3, 6, 9, 12, and18 must be constructed and screened for identifying those polypeptides having proteolytic activity, encompassed by the scope of the claims. An effective high-throughput process for mutating, cloning and expressing polypeptides as well as screening mutants would be necessary in order to identify mutants/variants having a proteolytic activity among an extremely large pool of polypeptide mutants of SEQ ID NOs: 21, 3, 6, 9, 12, or 18. However, the specification (page 17) only provides general information about mutagenesis of DNA for making amino acid substitution, deletion, and/or insertion mutations, and screening mutants for detecting activity of cloned mutagenized polypeptides. There is no disclosure in the specification about a completely automated high-throughput process for effectively mutagenizing coding-genes, cloning and expressing mutated polypeptides as well as effectively screening mutants for determining their proteolytic activities, thus identifying those mutants having amino acid substitutions, deletions and/or insertions which result in a desired proteolytic activity, from an extremely large pool of mutated polypeptides having up to 74 amino acid mutations in the 346 AA - 451 AA polypeptides of SEQ ID NOs: 21, 3, 6, 9, 12, and 18.
In order for the written description provision of 35 USC 112, first paragraph to be satisfied, Applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the 'written description' inquiry, whatever is now claimed. For example, MPEP 2163 states in part,
An adequate written description of a chemical invention also requires a precise definition, such as by structure, formula, chemical name, or physical properties, and not merely a wish or plan for obtaining the chemical invention claimed. See, e.g., Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 927, 69 USPQ2d 1886, 1894-95 (Fed. Cir. 2004) (The patent at issue claimed a method of selectively inhibiting PGHS-2 activity by administering a non-steroidal compound that selectively inhibits activity of the PGHS-2 gene product, however the patent did not disclose any compounds that can be used in the claimed methods. While there was a description of assays for screening compounds to identify those that inhibit the expression or activity of the PGHS-2 gene product, there was no disclosure of which peptides, polynucleotides, and small organic molecules selectively inhibit PGHS-2. The court held that “without such disclosure, the claimed methods cannot be said to have been described.”).
Without additional information, the skilled artisan cannot envision which specific substitutions, deletions and/or insertions of the polypeptide of SEQ ID NO: 21, 3, 6, 9, 12, or 18 would result in the claimed polypeptide having a proteolytic activity.
Therefore, the full breadth of a polypeptide having proteolytic activity and at least 80%, 81%, 85%, 90%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to SEQ ID NO: 21, 3, 6, 9, 12, or 18, encompassed by the claims, do not meet the written description provision of 35 USC 112, first paragraph.
Claim Rejections - 35 USC § 103
Claims 27, 32, and 40 are rejected under 35 U.S.C. 103 as being unpatentable over Lu-2 et al. (Uniport No. A0A368TW57, 2018, pages 1-3, of record) in view of Niyonzima et al. (Preparative Biochemistry & Biotechnology, 2014, Volume 45, Issue 3, pages 233-258, cited in IDS) and Gjermansen (WO2017064253, 2017, cited in IDS).
Lu-2 et al. teach a serine protease polypeptide in the bacterium Halomonas montanilacus isolated from Lake Pengyan at Tibetan, which has a sequence identity of 92.8% query match and 91.4% best local similarity to the sequence of SEQ ID NO: 3 in the claims 27 and 32 (see description in page 1 and the sequence in page 3 of Lu-2 et al., and also the sequence alignment between the polypeptide of SEQ ID NO:3 and the proteinase of Lu-2 et al. attached below).
The protease polypeptide taught by Lu-2 et al. differs from the claimed polypeptide composition in that Lu-2 et al. do not teach that their protease polypeptide is comprised in a composition along with a surfactant.
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Niyonzima et al. teach that proteases are important commercial enzymes used in detergent industries, as key components in detergent formulations; and the search for detergent-compatible proteases with better properties is a continuous exercise (abstract/lines 1-5). Niyonzima et al. also teach proteases to be used in detergent preparations must have stability in the presence of surfactants and have high activity at alkaline pH and in a broad temperature range (page 240/last para). Niyonzima et al. further teach a process of screening for detergent-compatible proteases, which includes culturing protease-producing microbes under optimized culture conditions, purifying proteases from microbial cultures, and examining effects of factors such as pH, temperatures, and surfactants on activity and stability of the proteases (page 241/paras 1-2, page 246/last para – page 247/para 4).
Gjermansen teaches the use of proteases or polypeptides having protease activity in detergents for cleaning such as dish wash and laundry, and the most commonly used proteases are serine proteases (page 1: lines 12-13 and 19-21). Gjermansen also teaches polynucleotides encoding the polypeptides, expression vectors or nucleic acid constructs for cloning the polynucleotides, and recombinant host cells comprising the polynucleotides in the constructs/vectors for expressing the polypeptides, as well as methods of producing the polypeptides in the host cells (pages: 1/lines 10-12, 2/lines 18-20, 15/lines 26-30, 19/lines 31-34, 22/lines 7-10, claims 14-16); and the techniques used for isolating and cloning polynucleotides for producing polypeptides having proteolytic activity are all known in the art (page 15, lines 3-10). Gjermansen further teaches that detergent compositions comprise proteases and other suitable cleaning/detergent relevant ingredients including surfactants and builders (pages: 26/lines 27-29, 29/lines 15-23, 31/lines 1-11, 48/lines 17-19).
It would have been obvious to one of ordinary skill in the art to combine the serine protease polypeptide taught by Lu-2 et al. with a surfactant for evaluating stability of the protease polypeptide in the presence of surfactant and determining whether the protease polypeptide is a detergent-compatible protease suitable for detergent preparations, thus arriving at a composition comprising the protease and surfactant. This is because Niyonzima et al. teach that proteases are important commercial enzymes and a key component in detergent formulations; the search for detergent-compatible proteases with better properties is a continuous exercise; and proteases to be used in detergent preparations must be tested for ensuring their stability in the presence of surfactants. In addition, Gjermansen teaches that serine proteases are the most commonly used proteases in detergent compositions. Thus, one of ordinary skill in the art would have been motivated to try the serine protease of Lu-2 et al. for identifying a detergent-compatible protease suitable for detergent preparations. Furthermore, the techniques for purifying the protease polypeptide of Lu-2 et al. from bacterial cells as well as cloning and expressing the protease in a host cell are well established in the art, as supported by Niyonzima et al. and Gjermansen. As such, the protease polypeptide of Lu-2 et al. is readily available for being combined with the surfactant for a detergent-compatible protease assay, which provides a reasonable expectation of success at combining the protease of Lu-2 et al. with a surfactant.
Regarding the limitation about the sequence identity to SEQ ID NO: 3 in the claims 27 and 32, Lu-2 et al. do not teach their protease has at least 93% sequence identity to SEQ ID NO: 3. However, the sequence identity between the protease of Lu-2 et al. and SEQ ID NO. 3 is close to a level of 93%, in view of that there are 92.8% query match and 91.4% best local similarity between these two sequences. Furthermore, the protease of Lu-2 et al. has a total of 412 amino acids matched to the 451 AAs-long polypeptide of SEQ ID NO: 3; and among the 39 mismatched amino acids there are 22 conserved mismatches, which are indicated as “:” in the sequence alignment attached above. The conserved mismatches include those between similar amino acids such as between glutamic acid (E) and glutamine (Q) or aspartic acid (D) as well as between valine (V) and leucine (L), specifically, E:Q (33), D:E (39), E:Q (147), E:D (285), D:E (320), D:E (350), E:D (388), E:Q (390), E:D (413), Q:E (450), and V:L (419) (Note: numbers in the parentheses represent locations of 11 mismatched amino acids at the “Qy” sequence, i.e. sequence of SEQ ID NO: 3, in the sequence alignment attached above). As such, It would have been obvious to try replacing the amino acid (e.g. Q, E, D, or L) at each of these mismatched locations with the corresponding similar amino acid (e.g. E, D, Q, or V) in the protease of Lu-2 et al. for further evaluating protease stability and identifying proteases more suitable for detergent preparations, thus arriving at the claimed proteinase having at least 93% identity to SEQ ID NO: 3 [Note: (412+11)/451= 93.7% identity], because these mismatched amino acids are highly similar to each other and the amino acid replacement facilitates identification of proteases more suitable for detergent preparations. 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, the claims 27 and 32 would have been obvious over the combined teachings of Lu-2 et al., Niyonzima et al., and Gjermansen.
Regarding Claim 40, it is a common practice in the art to add builders along with surfactants as cleaning/detergent relevant ingredients to the protease-containing compositions, as supported by Gjermansen. As such, it would have been obvious to further include a builder in the composition containing the protease polypeptide and surfactant suggested by the cite prior art for further evaluating stability of the protease polypeptide and determining whether the protease polypeptide is a detergent-compatible protease suitable for detergent preparations.
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.
Claims 27, 31, and 40 are rejected under 35 U.S.C. 103 as being unpatentable over Lu-3 et al. (Uniport No. A0A368U1V0, 2018, pages 1-2) in view of Niyonzima et al. (Preparative Biochemistry & Biotechnology, 2014, Volume 45, Issue 3, pages 233-258, cited in IDS) and Gjermansen (WO2017064253, 2017, cited in IDS).
Lu-3 et al. teach a serine protease polypeptide in Halomonas montanilacus bacterium isolated from Lake Pengyan at Tibetan, which has sequence identity of 95.3% query match and 94.9% best local similarity to the sequence of SEQ ID NO: 21 in claims 27 and 31 (see pages 1-2 for description and sequence of the protease, and also the sequence alignment between the polypeptide of SEQ ID NO:21 and the proteinase of Lu-3 et al. attached below).
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The protease polypeptide taught by Lu-3 et al. differs from the claimed polypeptide composition in that Lu-3 et al. do not teach that the protease polypeptide is comprised in a composition along with a surfactant.
The teachings of Niyonzima et al. and Gjermansen are described above.
It would have been obvious to one of ordinary skill in the art to combine the serine protease polypeptide taught by Lu-3 et al. with a surfactant for evaluating stability of the protease polypeptide in the presence of surfactant and determining whether the protease polypeptide is a detergent-compatible protease suitable for detergent preparations, thus arriving at a composition comprising the protease and surfactant. This is because Niyonzima et al. teach that proteases are important commercial enzymes and a key component in detergent formulations; the search for detergent-compatible proteases with better properties is a continuous exercise; and proteases to be used in detergent preparations must be tested for ensuring their stability in the presence of surfactants. In addition, Gjermansen teaches that serine proteases are the most commonly used proteases in detergent compositions. Thus, one of ordinary skill in the art would have been motivated to try the serine protease of Lu-3 et al. for identifying a detergent-compatible protease suitable for detergent preparations. Furthermore, the techniques for purifying the protease polypeptide of Lu-3 et al. from bacterial cells as well as cloning and expressing the protease in a host cell are well established in the art, as supported by Niyonzima et al. and Gjermansen. As such, the protease polypeptide of Lu-3 et al. is readily available for being combined with the surfactant for a detergent-compatible protease assay, which provides a reasonable expectation of success at combining the protease of Lu-3 et al. with a surfactant.
Regarding the limitation about the sequence identity to SEQ ID NO: 21 in the claims 27 and 31, Lu-3 et al. do not teach the protease has at least 96% sequence identity to SEQ ID NO: 21. However, the sequence identity between the polypeptide of SEQ ID NO: 21 and the proteinase of Lu-3 et al. is close to a level of 96% in view of that there are 95.3% query match and 94.9% best local similarity between the two sequences. Furthermore, the proteinase of Lu-3 et al. has a total of 356 amino acids matched to the 375 AAs-long polypeptide of SEQ ID NO: 21; and among the 19 mismatched amino acids there are 9 conserved mismatches, which are indicated as “:” in the sequence alignment attached above. The conserved mismatches include those between similar amino acids, such as between glutamic acid (E) and glutamine (Q) or aspartic acid (D) as well as between arginine (R) and lysine (K), Specifically, E:D (85), E:Q (135), D:E (153), E:D (216), D:E (276), and R:K (355) (Note: numbers in the parentheses represent locations of 6 mismatched amino acids at the “Qy” sequence, i.e. sequence of SEQ ID NO: 21, in the sequence alignment attached above). As such, It would have been obvious to try replacing the amino acid (e.g. D, Q, E, or K) at each of these mismatched locations with its corresponding similar amino acid (i.e. E, D, or R) in the proteinase of Lu-3 et al. for further evaluating protease stability and identifying proteases more suitable for detergent preparations, thus arriving at the claimed protease polypeptide having at least 96% identity to SEQ ID NO: 21 [Note: (356+6)/375= 96.5% identity], because these amino acids are highly similar to each other and the amino acid replacement facilitates identification of proteases more suitable for detergent preparations. 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, the claims would have been obvious over the combined teachings of Lu-3 et al., Niyonzima et al., and Gjermansen.
Regarding Claim 40, it is a common practice in the art to add builders along with surfactants as cleaning/detergent relevant ingredients to the protease-containing compositions, as supported by Gjermansen. As such, it would have been obvious to further include a builder in the composition containing the protease polypeptide and surfactant suggested by the cite prior art for further evaluating stability of the protease polypeptide and determining whether the protease polypeptide is a detergent-compatible protease suitable for detergent preparations.
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.
Claims 27, 33, and 40 are rejected under 35 U.S.C. 103 as being unpatentable over Groot (Uniport No. A0A1G8GTV3, 2017, cited in IDS) in view of Niyonzima et al. (Preparative Biochemistry & Biotechnology, 2014, Volume 45, Issue 3, pages 233-258, cited in IDS) and Gjermansen (WO2017064253, 2017, cited in IDS).
Groot teaches a periplasmic serine protease polypeptide from a Pseudomonas bacterium, which has sequence identity of 93.9% query match and 94.0% best local similarity to the sequence of SEQ ID NO: 6 in claims 27 and 33 (see page 1 of Groot, and also the sequence alignment between the polypeptide of SEQ ID NO. 6 and the proteinase of Groot, attached below). Overall, the protease of Groot has a total of 329 amino acids matched to the 349 AAs-long polypeptide of SEQ ID NO: 6 (see the sequence alignment below), accordingly giving a sequence identity of 94%, which meets the limitation of a polypeptide having at least 94% sequence identity to SEQ ID NO: 6 recited in the claim 27 and 33.
The protease polypeptide taught by Groot differs from the claimed polypeptide composition in that Groot does not teach the protease polypeptide is comprised in a composition along with a surfactant.
The teachings of Niyonzima et al. and Gjermansen are described above.
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It would have been obvious to one of ordinary skill in the art to combine the serine protease polypeptide taught by Groot with a surfactant for evaluating stability of the protease polypeptide in the presence of surfactant and determining whether the protease polypeptide is a detergent-compatible protease suitable for detergent preparations, thus arriving at the claimed composition. This is because Niyonzima et al. teach that proteases are important commercial enzymes and a key component in detergent formulations; the search for detergent-compatible proteases with better properties is a continuous exercise; and proteases to be used in detergent preparations must be tested for ensuring their stability in the presence of surfactants. In addition, Gjermansen teaches that serine proteases are the most commonly used proteases in detergent compositions. Thus, one of ordinary skill in the art would have been motivated to try the serine protease of Groot for identifying a detergent-compatible protease suitable for detergent preparations. Furthermore, the techniques for purifying the protease polypeptide of Groot from bacterial cells as well as cloning and expressing the protease in a host cell are well established in the art, as supported by Niyonzima et al. and Gjermansen. As such, the protease polypeptide of Groot is readily available for being combined with the surfactant for a detergent-compatible protease assay, which provides a reasonable expectation of success at combining the protease of Groot with a surfactant.
Regarding Claim 40, it is a common practice in the art to add builders along with surfactants as cleaning/detergent relevant ingredients to the protease-containing compositions, as supported by Gjermansen. As such, it would have been obvious to further include a builder in the composition containing the protease polypeptide and surfactant suggested by the cite prior art for further evaluating stability of the protease polypeptide and determining whether the protease polypeptide is a detergent-compatible protease suitable for detergent preparations.
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.
Claims 27, 34, and 40 are rejected under 35 U.S.C. 103 as being unpatentable over Pisa et al. (Uniport No. A0A433R972, 2017, pages 1-2) in view of Niyonzima et al. (Preparative Biochemistry & Biotechnology, 2014, Volume 45, Issue 3, pages 233-258, cited in IDS) and Gjermansen (WO2017064253, 2017, cited in IDS).
Pisa et al. teaches a trypsin-like serine protease polypeptide from a Cohnella bacterium, which has sequence identity of 80% query match and 78.5% best local similarity to the sequence of SEQ ID NO: 9 in claims 27 and 34 (see page 1 of Groot, and also the sequence alignment between the polypeptide of SEQ ID NO. 9 and the protease of Pisa et al., attached below).
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The protease polypeptide taught by Pisa et al. differs from the claimed polypeptide composition in that Pisa et al. do not teach that the protease polypeptide is comprised in a composition along with a surfactant.
The teachings of Niyonzima et al. and Gjermansen are described above.
It would have been obvious to one of ordinary skill in the art to combine the serine protease polypeptide taught by Pisa et al. with a surfactant for evaluating stability of the protease polypeptide in the presence of surfactant and determining whether the protease polypeptide is a detergent-compatible protease suitable for detergent preparations, thus arriving at a composition comprising the protease and surfactant. This is because Niyonzima et al. teach that proteases are important commercial enzymes and a key component in detergent formulations; the search for detergent-compatible proteases with better properties is a continuous exercise; and proteases to be used in detergent preparations must be tested for ensuring their stability in the presence of surfactants. In addition, Gjermansen teaches that serine proteases are the most commonly used proteases in detergent compositions. Thus, one of ordinary skill in the art would have been motivated to try the serine protease of Pisa et al. for identifying a detergent-compatible protease suitable for detergent preparations. Furthermore, the techniques for purifying the protease polypeptide of Pisa et al. from bacterial cells as well as cloning and expressing the protease in a host cell are well established in the art, as supported by Niyonzima et al. and Gjermansen. As such, the protease polypeptide of Pisa et al. is readily available for being combined with the surfactant for a detergent-compatible protease assay, which provides a reasonable expectation of success at combining the protease of Pisa et al. with a surfactant.
Regarding the limitation about the sequence identity to SEQ ID NO: 9 in the claims 27 and 34, Pisa et al. do not teach their protease has at least 81% sequence identity to SEQ ID NO: 9. However, the sequence identity between the polypeptide of SEQ ID NO: 9 and the protease of Pisa et al. is close to a level of 81% in view of that there are 80% query match and 78.5% best local similarity between the two sequences.
Furthermore, the protease of Pisa et al. has a total of 270 amino acids matched to the 344 AAs-long polypeptide of SEQ ID NO: 9; and among the mismatched amino acids there are 33 conserved mismatches, which are indicated as “:” in the sequence alignment attached above. The conserved mismatches include those between similar amino acids, such as between glutamic acid (E) and glutamine (Q) or aspartic acid (D), between arginine (R) and lysine (K), and between valine (V) and leucine (L) or isoleucine (I), Specifically, V:I (85), V:L (86), R:K (87), D:E (116), K:R (119), Q:E (151), V:I (157), Q:E (211), V:I (240), L:V (241), and D:E (273) (Note: numbers in the parentheses represent locations of 11 mismatched amino acids at the “Qy” sequence, i.e. sequence of SEQ ID NO: 9, in the sequence alignment attached above). As such, it would have been obvious to try replacing the amino acid (e.g. I, L, K, E, R, or V) at each of these mismatched locations with its corresponding similar amino acid (e.g. V, R, D, K, Q, or L) in the protease of Pisa et al. for further evaluating protease stability and identifying proteases more suitable for detergent preparations, thus arriving at the claimed proteinase having at least 81% identity to SEQ ID NO: 9 [Note: (270+11)/344= 81.6% identity], because these amino acids are highly similar to each other and the amino acid replacement facilitates identification of proteases more suitable for detergent preparations. 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, the claims would have been obvious over the combined teachings of Pisa et al., Niyonzima et al., and Gjermansen.
Regarding Claim 40, it is a common practice in the art to add builders along with surfactants as cleaning/detergent relevant ingredients to the protease-containing compositions, as supported by Gjermansen. As such, it would have been obvious to further include a builder in the composition containing the protease polypeptide and surfactant suggested by the cite prior art for further evaluating stability of the protease polypeptide and determining whether the protease polypeptide is a detergent-compatible protease suitable for detergent preparations.
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 objection to the specification in the response filed on 10/16/2025 (page 6) have been fully considered, but they are not persuasive. It is noted that the removal of the claim language from the specification is not sufficient to overcome the objection to the specification because the cited claim language is not the only issue in the specification. As indicated above, two distinct sets of paragraphs 1-40 are recited in the specification. Applicant failed to make appropriate correction, thus the objection is maintained.
Applicant's arguments about the 101 rejection in the 10/16/2025 response (pages 6-7) have been fully considered but they are not persuasive. In response to Applicant’s arguments about no naturally occurring counterpart to the claimed composition in page 7/para 1 of the response, the surfactant and polypeptide/protease in the claimed composition can co-exist together in the nature because they are both produced by naturally occurring microorganisms, as indicated above. In response to Applicant’s arguments based on the limitation that defines the form of the claimed composition, it is noted that the form of liquid, gel, powder, granulate, paste or spray recited in the claim 27 is at a high level of genericity, which appears to include all the possible forms of the composition (liquid, solid, semi-liquid, and semi-solid). Naturally occurring counterpart can be present in the form of liquid, solid, semi-liquid, and semi-solid. As such, the claim does not include additional elements that are sufficient to amount to significantly more than the judicial exception, as indicated above. With regard to Applicant’s further arguments based on good wash performance and stain removal of the claimed composition in page 7/para 1 of the response, these arguments are based on features not recited in the claims because there is no limitation in the claims to define wash performance and stain removal of the claimed composition. Furthermore, Examiner reminds Applicant that the instant claims do not recite any limitations to define concentrations or amounts of the surfactant and polypeptide/protease in the claimed composition. There is no factual evidence to support a composition comprising any amount of surfactant and protease can achieve the good wash performance and stain removal. Furthermore, naturally occurring proteinases has the property of digesting proteins, which could lead to removing a protein stain from a substance. There is no factual evidence to support that stain removal is a feature that distinguishes the claimed composition from its naturally occurring counterpart.
Applicant’s arguments about the claim rejections under 35 U.S.C. 112(b) or 112(d) in the 10/16/2025 response (page 7) have been fully considered, but they are moot because the rejections have been withdrawn as indicated above.
Applicant’s arguments about the rejection under 35 U.S.C. 112(a) as failing to comply with the written description requirement in the 10/16/2025 response (pages 7-9) have been fully considered, but they are not persuasive. The Examiner reminds Applicant that the instant claims 27-36 and 40 only define the polypeptide by a level of identity to a known amino acid sequence, but do not define any specific structure of the polypeptide (i.e. specific amino acids at specific location of the polypeptide). Because the mutations can be any types (substitution, deletion, and/or insertion) and occur at any locations of the claimed polypeptide, the claimed polypeptide is widely open to any structures. Furthermore, the claimed percent identity is not predictive of proteolytic activity, because the specification of the instant application does not provide any information about the structural - proteolytically functional relationship for the polypeptide of SEQ ID NOs: 21, 3, 6, 9, 12, or 18. In response to Applicant’s further arguments in the paragraph spanning pages 8 and 9, Examiner notes that it is possible for two proteins or mutants sharing 80-90% sequence identity to possess the same catalytic function. However, there is no data/evidence in the art or the specification to support any polypeptide mutants sharing 80-90% sequence identity would have the same catalytic/proteolytic activities. It is necessary for the specification to provide a structural-functional correlation for proteases of SEQ ID NOs: 21, 3, 6, 9, 12, and 18, so as to show which specific locations, regions, and amino acids throughout their entire amino acid sequence are essential for acquiring the claimed proteolytic activities. However, the specification does not disclose such information about structural-functional analysis. Finally, in response to Applicant’s arguments based on a working example shows proteinases are useful in detergents (in para 2 of page 9 of the response), it is noted that the proteinases used in the example are proteinases having 100% sequence identity to SEQ ID NO: 21, 12, 6, or 18, not the claimed polypeptide mutants having less than 100% identity. As such, the disclosure of the example does not provide any written description for claimed polypeptide mutants sharing 80% or more identity to SEQ ID NO: 21, 12, 6, or 18.
Applicant’s arguments about the rejection under 35 U.S.C. 103 over Lu-2 et al. in view of Niyonzima et al. and Gjermansen in the 10/16/2025 response (page 9) have been fully considered, but they are not persuasive. Examiner notes that even assuming sequence identity of the protease of Lu-2 et al. is calculated to be 91.4% by using the disclosed formula, the claimed polypeptide having at least 93% identity to SEQ ID NO: 3 (recited in the newly submitted claims 27 and 32) would still be obvious over the combined teachings of Lu-2 et al., Niyonzima et al., and Gjermansen, because more than half of the mismatched amino acids between Lu-2 et al. and SEQ ID NO: 3 are highly conserved and similar amino acids, and their replacement with each other would have been prima facie obvious. Overall, the conclusion of the obviousness of the new claims 27, 32, and 40 has been established for all the reasons indicated above (see pages 10-14 for details).
Applicant’s arguments about the rejection of the claim 23 under 35 U.S.C. 103 over Bergholz et al. in view of Niyonzima et al. and Gjermansen in the 10/16/2025 response (page 9) have been fully considered, but they are moot because the rejection has been withdrawn, as indicated above.
Conclusion
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 extension fee 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 date of this final action.
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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
/MANJUNATH N RAO/Supervisory Patent Examiner, Art Unit 1656