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 .
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-7, in the reply filed on 5/22/2026 is acknowledged.
Claims 8-11 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claims 1-7 have been examined on the merits herein.
Priority
Applicant’s claim for the benefit of a prior-filed application KR10-2022-0171948 filed 12/9/2022, under 35 U.S.C. 119(a)-(d) is acknowledged. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55 (priority documents electronically received on 5/14/2024).
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 1/6/2025 is acknowledged. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
The information disclosure statement filed 12/04/2023 fails to comply with 37 CFR 1.98(a)(3)(i) because it does not include a concise explanation of the relevance, as it is presently understood by the individual designated in 37 CFR 1.56(c) most knowledgeable about the content of the information, of each reference listed that is not in the English language. There is no English language translation for the cited foreign patent document KR-102251114-B1. A copy of the statement has been placed in the application file, but the information referred to therein has not been considered.
Drawings
The drawings were received on 4/8/2024. These drawings are acceptable.
Specification
The disclosure is objected to because of the following informalities:
The word “neoagarotetraos” appears in [0030] and [0074] of the specification dated 4/8/2024, and should instead be spelled “neoagarotetraose” (as in [0087]).
TRADE NAMES, TRADEMARKS, AND OTHER MARKS USED IN COMMERCE:
The use of the term “Ex Taq” (in [0080]), which is a trade name or a mark used in commerce (owned by Takara Bio), has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks (see MPEP 608.01(v) and 608.01(u)).
Appropriate correction is required.
Claim Objections
Claims 3 and 6 are objected to because of the following informalities:
In claim 3, line 2, the phrase “the partial hydrolysis is reacting at” is improper grammar and should instead say “the partial hydrolysis is performed at” .
In claim 6, line 2, the word “neoagarotetraos” should instead be “neoagarotetraose” .
Appropriate correction is required.
Claim Rejections - 35 USC § 112(a) - Written Description
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 and 3-7 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 claims 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 1 recites a method for preparing an agar partial hydrolysis product having hyaluronidase inhibitory activity, the method comprising partially hydrolyzing agar by adding an agarase.
Claim 2 recites that the agarase consists of an amino acid sequence represented by SEQ ID NO: 2.
The dependent claims 3-4 do not practically limit the encompassed agarase.
Claims 5-7 are drawn to an agar partial hydrolysis product having hyaluronidase inhibitory activity prepared by the method of claim 1, and further properties thereof.
The claims thus encompass any and all agarases that may be used for preparing an agar partial hydrolysis product. To achieve the recited functional property of ” having hyaluronidase inhibitory activity”, a particular amount of hydrolysis must have occurred, without the full hydrolysis of the agar starting material, according to the instant disclosure.
According to the B.R.I. of the claim, when viewed in light of the specification, there exists a nearly limitless number of structures of the enzyme and sequences thereof within the claimed scope. Comparatively, the specification only recites using a single species of the broad genus that meets the recited limitations.
MPEP § 2163.(II)(A)(3)(a) states that 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 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 the inventor was in possession of the claimed genus. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
The specification fails to reasonably describe the full genus of the claimed invention by providing identifying characteristics or functional properties of agarases which would yield a product with the recited properties.
The specification states, generally, that there are two families of agarases that degrade agar, including α-agarases and β-agarases, which yield distinct products ([0010]). The enzymes are only described in terms of functional activity. No description of critical structures or identification of key sequence motifs which may link sequences to the desired activities have been provided. The instant specification does not disclose relevant identifying characteristics, such as key structural or other physical properties, or functional characteristics coupled with a known or disclosed correlation between function and structure, such that the entirety of the claimed genus is encompassed by the description in the disclosure. There is no discussion of the breadth of agarases nor mention of sources from which desirable enzymes can be obtained.
From a review of the state of the art, it is apparent that multiple sources of agarases are known. “Fu” (Fu, X.T.; Kim, S.M. “Agarase: Review of Major Sources, Categories, Purification Method, Enzyme Characteristics and Applications”. Mar. Drugs 2010, 8, 200-218. doi.org/10.3390/md8010200) is a review article describing naturally occurring agarases and their role in hydrolyzing agar to its polysaccharide constituents (Abstract). Fu teaches that agarases have been isolated from different genera of bacteria found in seawater and marine sediments (Abstract, Table 1). These mostly appear to be marine organisms, of which there are an incredible and vast amount of biodiversity. There is no manner in which to predict if any and all agarases, including variants, derivatives, and yet-undiscovered agarases can be used in the claimed method, as encompassed by the breadth of the claimed scope.
The specification describes an embodiment that comprises hydrolyzing agar with recombinant Gaa16B (rGaa16B), derived from Gaa16B (NCBI accession No. KP716980) from Gilvimarinus agarilyticus JEA5 ([0077]). Gaa16B is an agarase consisting of an amino acid sequence represented by SEQ ID NO: 2 ([0031]), and is demonstrated herein to produce a partial hydrolysis product with desirable characteristics.
The examples in the specification include only one working example using Gaa16B (SEQ ID NO: 2), which is used to produce a partial agarase product having an inhibitory effect on hyaluronidase (see [0080]-[0107]; Tables 1 and 2). The enzyme is only used at a concentration of 0.1 unit/mL and reacted at 55°C for 5, 10, 20, 30, and 60 minutes to yield the PHP5, PHP10, PHP20, PHP30, and PHP60 products described herein.
However this is a description of a single embodiment of the claimed genus, and there is no known or disclosed relationship between the sequence and function that is sufficient to fulfill the written description requirement for the entire claimed genus.
Thus, the specification provides only one example of the claimed genus, which cannot be considered a sufficient description of a representative number of species by actual reduction to practice of the full breadth of the vast genus. There is no evidence that, at the time of filing, the Applicant possessed additional representative species of the full genus recited in the claims beyond those provided in the working examples.
For these reasons, the disclosure fails to provide adequate written description to support the entirety of the broad genus claim to methods using any and all agarases to produce the partial hydrolysis product.
Claim 1 are thus rejected under 35 U.S.C. § 112(a) because the claimed subject matter is not described in the specification in such a way as to reasonably convey to a skilled artisan that the inventor, or a joint inventor, had possession of the claimed invention.
The dependent claims 3-7 are also rejected under 35 U.S.C. § 112(a), because these claims require the method using any of the broad genus of agarases according to claim 1, and fail to practically further limit the claimed invention.
Claim 2 recites that the agarase consists of an amino acid sequence represented by SEQ ID NO: 2, and this claim scope is supported by reduction to practice in the instant disclosure.
Claim Rejections - 35 USC § 112(b)
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 1-7 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.
The terms “agar partial hydrolysis product” and “partially hydrolyzing” in claim 1 are relative terms which renders the claim indefinite. The terms “agar partial hydrolysis product” and “partially hydrolyzing” are 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. There is no description of how much hydrolysis is necessary to fulfill the claim scope limitation. It is unclear how the amount of partial hydrolysis is meant to be determine. Because the terms “partial” and “partially” are relative terms and there is no clear definition of how the amount of partial hydrolysis is to be determined, one cannot determine the metes and bounds of the claimed invention.
In the specification, paragraph [0026] describes “In the present disclosure, the partial hydrolysis refers to incomplete hydrolysis until the agar is completely hydrolyzed and homogenized into low molecular substances, and may be achieved by controlling hydrolysis conditions, such as temperature and time.” Further, paragraph [0029] states: “According to the method of the present disclosure, the partial hydrolysis product of the present disclosure, the obtained product refers to a product which is not completely hydrolyzed and homogenized into low molecular materials, but includes high molecular materials of various molecular weights with a polydispersity (Mw/Mn) value of 3 to 8, preferably 5 to 7, and thus, has superior hyaluronidase inhibitory activity to a complete hydrolysis product. Even when reading the specification, there is no clear definition for what amounts to a partial hydrolysis.
The term can be interpreted at least two ways. One is that there is still some amount of the remaining starting agar (i.e. the starting material not 100% hydrolyzed). The other interpretation is that the hydrolysis products are not completely hydrolyzed into the smallest saccharide constituents. Thus claim 1 and all claimed dependent thereof are found indefinite.
Claims 5-7 are found indefinite for essentially the same reason as described for claim 1-4. Claim 5 requires an agar partial hydrolysis product. This product appears to comprises certain products such as neoagarotetraose, neoagarohexaose, and neoagarobiose, and/or similar high molecular materials of various molecular weights. However, because of the problems identified above with the relative term “partial” there is no way to determine the metes and bounds which define the agar partial hydrolysis product. Does the claim require there to be any of the starting material remaining? Does the term partial refer to the completeness of the reaction or to the amount of further hydrolysis into smaller saccharides?
In addition, claim 6 recites “the agar partial hydrolysis product comprises more neoagarotetraose (NA4) and neoagarohexaose (NA6) than neoagarobiose (NA2)”. This limitation is indefinite because it is unclear whether this requires that the sum of NA4 and NA6 together is more than the amount of NA2, or if this limitation requires that both each of NA4 and NA6 is separately greater than the amount of NA2. Further, the claim does not indicate if this is by percent weight, percent of molecules detected, or some other measure of the amount of the products. This is critical because the molecular weight of NA2 is less than NA4 and NA6, due to the differences in the polymer size. Therefore, the metes and bounds of this claim are not measurable and the claim is indefinite.
Therefore, claims 1-7 are rejected under 35 U.S.C. § 112(b) for failing to particularly point out and distinctly claim the Applicant’s invention.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 5-7 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural product without significantly more.
For determining subject matter eligibility, the following analysis was considered, per MPEP § 2106.
Patent Eligibility Analysis Step 1: Step 1 of the eligibility analysis asks: is the claim to a process, machine, manufacture or composition of matter? Yes, the claims are directed to a composition: an agar partial hydrolysis product. (Claims 5-7, STEP 1: YES).
Patent Eligibility Analysis Step 2A Prong 1: Step 2A, prong 1 asks: does the claim recite an abstract idea, law of nature, or a natural phenomenon (product of nature)?
Claims 5-7 each require an agar partial hydrolysis product. Agar is a natural product, and is a major component of the cell wall of red seaweed (see [0010] of the specification). Due to the B.R.I. of the claims, a “partial hydrolysis product” includes the natural agar (the non-hydrolyzed agar). Claim 5 is thus directed to the partial hydrolysis products of agar, comprising agarose, agaropectin, and the polysaccharides neoagarotetraose (NA4), neoagarohexaose (NA6), and neoagarobiose (NA2). The specification states that “α-agarase hydrolyzes α-1,3-linkages of agarose to generate agarooligosacchride (AOS) and β-agarase hydrolyzes β-1,4-linkage to generate neoagaro-oligosaccharides (NAOS)” ([0010]). Further, the B.R.I. of the products of agarose include the saccharides D-galactose and 3,6-anhydro-L-galactopyranose (see [0010]).
Thus, the B.R.I. of the claims include limitations encompassing natural products including at least the neoagarooligosaccharides neoagarotetraose (NA4), neoagarohexaose (NA6), and neoagarobiose (NA2) as well as the base constituents D-galactose and 3,6-anhydro-L-galactopyranose (see also Figs. 2A and 2B of the instant application).
When a claim recites a nature-based product limitation, the markedly different characteristics (MDC) analysis is used to determine whether the natural product has markedly different characteristics from its natural counterpart (see MPEP 2106.04(c)). MPEP § 2106.04(c) explains “Where the claim is to a nature-based product produced by combining multiple components, the markedly different characteristics analysis should be applied to the resultant nature-based combination, rather than its component parts.”
In this case, the appropriate natural counterpart for the polysaccharides of claims 5-7 would be at least one of naturally occurring neoagarotetraose (NA4), neoagarohexaose (NA6), and neoagarobiose (NA2), D-galactose, and 3,6-anhydro-L-galactopyranose.
The second step in the MDC analysis is to identify appropriate characteristics to compare. Appropriate characteristics can be expressed as the nature-based product’s structure, function, and/or other properties, and are evaluated on a case-by-case basis. In this case, the appropriate characteristics include: the structure and functional properties of the hydrolysis products. The final step in the markedly different characteristics analysis is to compare the characteristics of the claimed nature-based product to its naturally-occurring counterpart in its natural state, in order to determine whether the characteristics of the claimed product are markedly different. The courts have emphasized that to show a marked difference, a characteristic must be changed as compared to nature, and cannot be an inherent or innate characteristic of the naturally-occurring counterpart or an incidental change in a characteristic of the naturally occurring counterpart. Myriad, 569 U.S. at 580, 106 USPQ2d at 1974-75. Thus, in order to be markedly different, the inventor must have caused the claimed product to possess at least one characteristic that is different from that of the counterpart (MPEP § 2016.04(c).II.C.). If there is no change in any characteristic, the claimed product lacks markedly different characteristics, and is a product of nature exception.
“Fu” (Fu, X.T.; Kim, S.M. “Agarase: Review of Major Sources, Categories, Purification Method, Enzyme Characteristics and Applications”. Mar. Drugs 2010, 8, 200-218. doi.org/10.3390/md8010200) is a review article describing naturally occurring agarases and their role in hydrolyzing agar to its polysaccharide constituents (Abstract). Fu teaches that agarases have been isolated from different genera of bacteria found in seawater and marine sediments (Abstract, Table 1). Fu discusses that β-agarases cleave β-1,4 linkages to produce neoagarooligosaccharides of series related to neoagarobiose (pg. 200, last sentence).
This review states that “Because agarases are the enzymes that hydrolyzes agar, they have been isolated from the surface of rotted red algae in the South China Sea coast in Hainan Island [21], decomposing algae in Niebla in Chile [22] and in Halifax in Canada [23], and decomposing Porphyra in Japan [24]. Some marine mollusks live on seaweed, thus the microorganisms in their digestive tract produce carbohydrate hydrolases, such as agarases.” (Section 3.1. Sources of Agarases on pg. 202). Therefore, this reference teaches that naturally occurring agarases are found on decomposing agar in nature and the resulting products when these agarases digest natural agar are also thus naturally occurring. Table 1 describes that NA2, NA4, NA6 are all observed products of the natural marine organism agarases. To this extent, Fu also teaches that “oligosaccharides have been prepared from agar by crude agarase from Vibrio QJH-12 isolated from the South China Sea coast [4]. The oligosaccharides mixture exhibit antioxidative activities in scavenging hydroxyl free radical, scavenging superoxide anion radical, and inhibiting lipid peroxidation”. (pg. 213, 6.2. Production of Agar-Derived Oligosaccharides).
“Cheong” (Cheong, Kit-Leong et al. “Oligosaccharides Derived from Red Seaweed: Production, Properties, and Potential Health and Cosmetic Applications.” Molecules (Basel, Switzerland) vol. 23,10 2451. 25 Sep. 2018, doi:10.3390/molecules23102451) discusses the use of oligosaccharides derived from natural sources as functional ingredients in human nutrition, and states that red seaweed, a proven rich source of agar and carrageenan, is one of the most abundantly present sources of such oligosaccharides (Abstract). Cheong discloses the existence of carrageenan-oligosaccharides (COS), agar-oligosaccharides (AOS), and neoagaro-oligosaccharides (NAOS) (see e.g. Figure 1). Cheong states that “Since naturally occurring AOS and COS are scarce in number, in vitro de-polymerization of red seaweed polysaccharides is often resorted to as a reliable strategy for producing oligosaccharides” (pg. 4, first sentence). Thus, it appears in the art that there are naturally occurring partial hydrolysis products, including the natural polysaccharides and oligosaccharides which make up agar. Even if certain of the neoagarooligosaccharides exist in only trace amounts, these are still natural products and the products of the instantly claims are not markedly different from these occurring in nature.
MPEP §2106.04(b).II. states that “It is important to keep in mind that product of nature exceptions include both naturally occurring products and non-naturally occurring products that lack markedly different characteristics from any naturally occurring counterpart. See, e.g., Ambry Genetics, 774 F.3d at 760, 113 USPQ2d at 1244 ("Contrary to Myriad's argument, it makes no difference that the identified gene sequences are synthetically replicated. As the Supreme Court made clear, neither naturally occurring compositions of matter, nor synthetically created compositions that are structurally identical to the naturally occurring compositions, are patent eligible.")”. The instant claims 5-7 encompass partial hydrolysis products that are essentially the same as the naturally occurring products, including NA2, NA4, NA6, and other possible smaller products such as D-galactose.
No characteristics of the naturally-derived saccharides are markedly changed by the described hydrolysis. Because these products can be found in nature, and can be made by completely natural processes, they are no different than the naturally-occurring saccharides. The individual components of the agarose are thus naturally derived products. The claims encompass the hydrolysis product of D-galactose, which is a natural product, having no differences than D-galactose obtained from any other source.
When considered as a whole, there is no evidence or suggestion that the claimed product has any markedly different characteristic than the individual naturally occurring products.
Therefore, the claimed product lacks markedly different characteristics, and is a product of nature exception (Claims 5-7, Step 2A, Prong 1: YES).
Patent Eligibility Analysis Step 2A Prong 2: Step 2A, prong 2 asks: does the claim recite additional elements that integrate the judicial exception into a practical application?
Claims 5-7 do not recite any additional elements other than the product of nature exception, specific limitations regarding the natural compositions and functional limitations thereof (i.e. that there exists a higher amount of NA4 and NA6 than NA2). The recitation of “having hyaluronidase inhibitory activity” (recited in the preamble of the claims) amounts to a functional limitation of a characteristic due to the innate properties of the natural product.
Claim 7 recites that the polydispersity is from 3 to 8 Mw/Mn, but this doesn’t differentiate the claims from the natural product(s), nor does it recite a practical application thereof. Instead this is a recitation of a particular property or just merely a measurement of the product. This does not integrate the judicial exception into a practical application as these functional limitations merely reflects innate capabilities of the natural product, and does not require a particular or directed application. There is no particular application or implementation of the natural product recited.
Therefore, the judicial exception is not integrated into a practical application because the claims do not recite any additional elements other than the naturally-occurring product(s) and innate functional characteristics thereof (Claims 5-7, Step 2A, Prong 2: NO).
Patent Eligibility Analysis Step 2B: Does the claim recite additional elements that amount to significantly more than the judicial exception?
Claims 5-7 do not recite any additional elements that amount to more than the ineligible natural product. There is no particular implementation or transformation, nor any inventive concept that results in significantly more than the natural products, as a whole. The recitation of “having hyaluronidase inhibitory activity” does not amount to more than the judicial exception.
Claim 6 recites that there exists a higher amount of NA4 and NA6 than NA2, but as explained above under Step 2A, Prong 1, these are natural products that occur from natural decomposition processes. It is noted that adjustments or optimization of a concentration of a completely natural product does not result in any particular transformation of the ineligible natural product, nor does such adjustment of concentration constitute an inventive concept.
Claim 7 recites that the polydispersity is from 3 to 8 Mw/Mn. This appears to be a natural property of a product that results from a completely natural process (i.e. the hydrolysis of agar by naturally co-occurring enzymes), as described in the Fu et al. reference above). There is no evidence that a natural product does not have these features. Such a limitations does not practically limit the claims to anything other than the natural products, instead these merely recite specific elements or functional properties of the product, discovered by the measurements described in the instant disclosure. Any naturally occurring agar or agarose will be a mixture of polysaccharides and natural degradation of which will affect the polydispersity in the mixture.
When considered individual or in combination, the claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception (Claims 5-7, Step 2B: NO).
As such, claims 5-7 do not qualify as eligible subject matter. For these reasons the claims are rejected under section 101 as being directed to non-statutory subject matter.
Claim Rejections - 35 USC § 102
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.
Claims 1-5 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Hong OC, et al. (KR-101796060-B1 to KOREA INST OCEAN SCI & TECH: an English language translation of which is also included with this action).
Hong et al. discloses agarases which perform the hydrolysis of agar to produce neo-agar oligosaccharides (Abstract, claims 1, 9 and 10), as recited in the instant claim 1.
Hong et al. teaches an agarase obtained from Gilvimarinus agarilyticus JEA5 (the Gaa16B protein; pg. 4, last paragraph - pg. 5, first paragraph of the provided English translation), comprising SEQ ID NO: 2, which is 100% identical to that of the instant SEQ ID NO: 2 (an alignment of which is included at end of this action). In Hong et al., the agarase Gaa16B, which consists of the exact sequence of the instantly claimed SEQ ID NO: 2, is produced recombinantly and reacted with agar substrate to test its total agarase activity (pg. 8, 3rd paragraph of the provided translation: “In order to confirm the intracellular total activity in Gaa16B, MGaa16B and MGaa16B-C, the over-expressed cells were pulverized by ultrasonication and the agarase activity was measured with supernatant. After incubation at 55°C for 10 minutes, 3,5-dinitrosalicylic acid (DNS) was added, boiled at 100 ° C for 20 minutes... 570 nm Absorbance was measured and colorimetric was determined. The amount of enzyme producing 1 μmol of reducing sugar per minute was expressed as 1 unit.”). The reference demonstrates that the Gaa16B preparation had 0.47 unit/ml of agarase activity (pg. 8, 4th paragraph of the provided translation). This Gaa16B agar hydrolyzing activity, although lesser than the other derivatives taught in Hong, is considered to fulfill the limitations of claim 2.
Hong also teaches the generation and application of derivates of Gaa16B, including the enzymes termed “MGaa16B” and “MGaa16B-C” (Fig. 1; pg. 5 “Preparation and Sequence Analysis of MGaa16B”; and pg. 6 “Preparation and Sequence Analysis of MGaa16B-C”). These enzymes are further tested for agar hydrolysis activity, and MGaa16B-C is demonstrated to produce partial hydrolysis products comprising various neo-agar oligosaccharides (Figure 8).
Therefore, Hong et al. discloses the instantly claimed method of claims 1 and 2, including an agarase having the sequence of SEQ ID NO: 2 as recited herein. The agarases taught in Hong are incubated with an agar substrate and produces at least a partial hydrolysis product (i.e. any product resulting from agar hydrolysis, according to the B.R.I. as discussed above). Hong et al. discloses that such products include polysaccharides such as neo-agar oligosaccharides.
Regarding the preamble recitation of “an agar partial hydrolysis product having hyaluronidase inhibitory activity” and the product-by-process of claim 5, it is predictable that products produced by essentially identical methods predictably have the same functional properties, including the ability to inhibit hyaluronidase, as recited in the preamble of the claim.
Regarding claims 3 and 4, Hong et al. recites that the reaction can be performed at “at 55°C for 10 minutes” and then the mixture was “boiled at 100° C for 20 minutes” (pg. 8, 3rd paragraph of the provided translation), which is amounts to a step of inhibiting the enzymes. Further, other recombinant GaaB16 derivate agarases were used for further tested at times between 1 and 120 minutes (“recombinant MGaa16B-C was incubated at 55, 60, and 65 ° C for 30, 60, 90, and 120 minutes”, pg. 9, 5th paragraph of the provided translation, Example 4).
Thus, the disclosure of Hong et al. (KR-101796060-B1) is considered to anticipate the instantly claimed method of claims 1-4 and the product-by-process of claim 5, according to the B.R.I. of the instant claims.
Claim Rejections - 35 USC § 102/103
The text of the relevant sections of 35 U.S.C. § 102 can be found above.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1 and 3-7 are rejected under 35 U.S.C. 102(a)(1) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Lin et al. (“Simple Preparation of Diverse Neoagaro-Oligosaccharides. Processes 2019, 7, 267. doi.org/10.3390/pr7050267).
Lin et al. discloses a method for obtaining pure and well-defined oligosaccharides was established by hydrolyzing agar with β-agarase from Vibrio natriegens (Abstract). The method of Lin comprises hydrolyzing agar with the β-agarase for defined lengths of time (Figure 3; “Neoagaro-oligosaccharides with different degrees of polymerization were obtained by hydrolyzing agar with β-agarase for different lengths of time” (see Abstract).
The reactions of Lin produce mixtures of products including neoagarobiose (NA2), neoagarotetraose (NA4), neoagarohexaose (NA6), neoagarooctaose (NA8), neoagaro-decaose (NA10) and neoagarododecaose (NA12) (see Abstract, Figure 3, Table 2). The relative amount of these products (which are, undoubtably, partial hydrolysis products) varied based on the time of the reaction, as demonstrated in Table 2 (“The enzymolysis products were found to be composed of NA2, NA4, NA6, NA8, NA10 and NA12 with yields of 5.0, 38.9, 18.1, 16.8, 13.8 and 2.5 mg/100 mg, respectively after the agar was hydrolyzed by β-agarase for 4 h” on pg. 5).
Lin states that “Therefore, desired NOAS with different DP could be obtained by controlling the enzymolysis time, which may be beneficial to the further studies on NAOS” (pg. 7, first ¶).
Thus, Lin discloses the instantly claimed method of partially hydrolyzing agar using an agarase enzyme.
The instant claim 1 recites in the preamble that the product has hyaluronidase inhibitory activity, which is a functional feature in the preamble, amounting to an intended use.
Regardless, because Lin teaches a process yielding products which are essentially identical to that of the instant claims, there is substantial evidence to predict that the products of Lin would also have hyaluronidase inhibitory activity, if so tested. The partial hydrolysis products of Lin include the same compounds as those disclosed in the instant invention (i.e. neoagarobiose (NA2), neoagarotetraose (NA4), neoagarohexaose (NA6)), having the hyaluronidase inhibitory activity.
MPEP § 2112.01 discusses that “Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). "When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). Therefore, the prima facie case can be rebutted by evidence showing that the prior art products do not necessarily possess the characteristics of the claimed product. In re Best, 562 F.2d at 1255, 195 USPQ at 433. See also Titanium Metals Corp. v. Banner, 778 F.2d 775, 227 USPQ 773 (Fed. Cir. 1985)”. Further,
Regarding claim 3, Lin discloses the optimization of multiple enzymatic hydrolysis conditions, including reaction temperature (30, 35, 40, 45, 50, 55 and 60 °C), pH (6.0, 6.5, 7.0, 7.5, 8.0, 8.5 and 9.0), reaction time (1, 5, 10, 15, 20, 25 and 30 h), substrate concentration (0.1, 0.2, 0.3, 0.4, 0.5, 0.6 and 0.7%) and enzyme amounts (20, 40, 60, 80, 100, 120 and 140 U/g) (section 2.2. Optimization of Enzymatic Hydrolysis Condition). Lin thus discloses a method wherein the temperature of the reaction is within the claimed range of 1 - 100°C and at least one tested time of 60 minutes (e.g. 1 hour).
Regarding claim 4, Lin states that the reaction is inactivated by incubation in a boiling water bath (thus around 100°C) for 15 min.
Regarding claim 5, Lin teaches a partial hydrolysis product comprising the degradation products of neoagarobiose (NA2), neoagarotetraose (NA4), neoagarohexaose (NA6) and others, that is produced by essentially the same process as that of the instant claims.
Regarding claim 6, many of the hydrolysis product mixtures shown in Table 2 of Lin have more NA4 and NA6 than NA2 (including E, which has no NA6 but yet still has more NA4 than NA2).
Regarding claim 7, the exact of amount of the polydispersity is not disclosed in Lin. However, based upon the claim language and the formula provided in the instant disclosure (see... of the specification), it is evident that the product mixtures in Lin have multiple amounts of the different higher molecular weight species (such as samples A and B in Figure 3) will have a polydispersity around the same amount as that which is instantly claimed. Because the method and products produced in Lin are essentially identical to the method and product of the instant claims, the polydispersity and other characteristics will predictably be of or around the same as that which is instantly claimed, absent convincing evidence to the contrary.
In the alternative, even if the composition (with respect to the polydispersity or functional properties) is not identical to the referenced composition and effects, with regard to some unidentified characteristics, the differences between that which is claimed and that which is disclosed, is so slight that the referenced composition is likely to inherently possess the same characteristics of the claimed composition, particularly in view of the similar characteristics which they have been shown to share and by the functions of the component materials (e.g. the presence of neoagaro-oligosaccharides including neoagarobiose (NA2), neoagarotetraose (NA4), neoagarohexaose (NA6), neoagarooctaose (NA8), neoagaro-decaose (NA10)) which are inherently present in each and which functions are inclusive of those appreciated in the instant disclosure as being present (see MPEP 2112.02 at Ex parte Novitski, in reference to reference-silent functioning of biological materials providing anticipation of the functions based upon the material itself (noting the reference of “Dart” therein did not appreciate the claimed function but still anticipated the function based on the inherent function of the material, and that the Applicant’s disclosure appreciating the function upon usage thereof as further evidence of the presence of the function).
Thus, a method comprising treating agar with an agarase to produce a partial hydrolysis product, the produced partial hydrolysis product, and the functional properties thereof, including the recited hyaluronidase inhibition, would have been anticipated, or in the alternative, at least obvious to those of ordinary skill in the art within the meaning of 35 USC § 103 over the disclosure of Lin, for all of the reasons discussed above.
From the teachings of the reference, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in performing the claimed method and producing a partial hydrolysis product, as an identical method yielding a product having substantially the same composition is disclosed in Lin.
Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date, as evidenced by the references, especially in the absence of evidence to the contrary.
Accordingly, the claimed invention as a whole was at least prima facie obvious, if not anticipated by Lin, especially in the absence of sufficient, clear, and convincing evidence to the contrary.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1 and 5-7 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, and 5 of copending Application No. 19/099,080 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the claimed subject matter of the reference application anticipates and overlaps substantially with the instant claims.
Claim 1 of the reference application recites “a method for producing neoagarotetraose (NA4) and neoagarohexaose (NA6), the method comprising enzymatically degrading a substrate by treating the same with a GH16B β-agarase comprising SEQ ID NO: 1.” This GH16B β-agarase anticipates the general agarase required in the instant claim 1. Claim 3 of the reference claim recites that the substrate may be agarose. The method of the reference application thus anticipates the instantly recited method. The product produced in the reference method comprises neoagarotetraose (NA4) and neoagarohexaose (NA6), which are agar partial hydrolysis products, according to the instant disclosure. These would thus predictably have all of the same innate characteristics and functional properties of the instantly recited agar partial hydrolysis products.
Regarding the product-by-process claims of 5-7, the reference claims encompass a method that results in a product comprising neoagarotetraose (NA4) and neoagarohexaose (NA6). This product thus anticipates the partial hydrolysis product of claim 5, as described above, because it is essentially identical to the compounds which are instantly claimed.
Regarding claim 6, the recited method yields a product (i.e. product-by-process) that has NA6 and NA4, with substantially no NA2 as evidenced by Fig. 9 of the disclosure.
MPEP §804.II.B.1. establishes that "The Patent and Trademark Office (‘PTO’) determines the scope of the claims in patent applications not solely on the basis of the claim language, but upon giving claims their broadest reasonable construction ‘in light of the specification as it would be interpreted by one of ordinary skill in the art.’ " Phillips v. AWH Corp., 415 F.3d 1303, 1316, 75 USPQ2d 1321, 1329 (Fed. Cir. 2005) (en banc) (quoting In re Am. Acad. of Sci. Tech. Ctr., 367 F.3d 1359, 1364, 70 USPQ2d 1827, 1830 (Fed. Cir. 2004);” and also describes that “the portion of the specification of the reference that describes subject matter that falls within the scope of a reference claim may be relied upon to properly construe the scope of that claim. In particular, when ascertaining the scope of the reference’s claim(s) to a compound, the examiner should consider the reference’s specification, including all of the compound’s uses that are disclosed. See Sun Pharm. Indus., 611 F.3d at 1386-88, 95 USPQ2d at 1801-02.” Further, MPEP §804.II.B.1. also states that “If the reference patent discloses several species within the scope of the reference genus claim, that portion of the disclosure should be analyzed to properly construe the reference patent claim and determine whether it anticipates or renders obvious the claim in the application being examined”.
Thus, the specification and figures are used to determine the structural and chemical constituents of the product recited in the claims of the reference application. The product is thus determined to substantially overlap with the product-by-process recited in claim 6.
Regarding claim 7, due to the presences of both NA6 and NA4, and the substantial overlap with the instantly recited product, the method and produced product of the reference application is deemed to predictably have the same properties as that which is instantly claimed, if so tested. Further, the optimization of properties and dispersion of polymers would be a matter of routine optimization to one having ordinary skill in the art. Thus, claim 7 would have been obvious over the subject matter of the reference claim 19/099,080.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Citation of Pertinent Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Hong, S.J. et al. (“In vitro and in vivo investigation for biological activities of neoagarooligosaccharides prepared by hydrolyzing agar with β-agarase”. Biotechnol Bioproc E 22, 489–496., 2017) discloses three neoagarooligosaccharides (NAOs), neoagarobiose (NA2), neoagarotetraose (NA4), and neoagarohexaose (NA6) prepared by hydrolyzing agar with recombinant β-agarases, DagA and DagB, from Streptomyces coelicolor A3(2) (see Abstract). Hong teaches that NAO treatment resulted in significant inhibition of α-glucosidase, with the strongest effect observed in a NA4 and NA6 mixture (Abstract, Figure 4).
Li et al. ("A simple method of preparing diverse neoagaro-oligosaccharides with β-agarase." Carbohydrate research 342.8, 2007, 1030-103) discloses preparation of oligosaccharides from agarose using degradation with recombinant β-agarases (having EC 3.2.1.81) including AgaA and/or AgaB (Abstract). The hydrolysis products disclosed in Li et al. include DP12, neoagarododecaose; DP10, neoagarodecaose; DP8, neoagaro-octaose; DP6, neoagarohexaose; and DP4, neoagarotetraose (Figure 1).
Conclusion
Claims 1-7 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ANDREW TERRY MOEHLMAN whose telephone number is (571)270-0990. The examiner can normally be reached M-F 9am-5pm EST.
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/A.T.M./Examiner, Art Unit 1655
/ANAND U DESAI/Supervisory Patent Examiner, Art Unit 1655
Appendix A: Alignment of SEQ ID NO: 2 with SEQ ID NO: 2 from Hong et al.
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