DETAILED CORRESPONDENCE
Status of the Application
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 11-21 are pending in this application.
Applicant’s amendment to the claims filed 02/27/2026 is acknowledged. This listing of the claims replaces all prior versions and listings of the claims.
Applicant’s remarks filed on 02/27/2026 in response to the non-final rejection mailed on 09/03/2025 are acknowledged and have been fully considered.
Claims 22-23 are canceled and the rejection previously applied to these claims is withdrawn.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Election
The elected subject matter is
Group I, corresponding to pending claims 11-18 and 21, drawn to the technical feature of a method for manufacturing a proteoglycan-containing composition, comprising a freezing step, a free-drying step, and an extraction step,
elected during a telephone conversation with Keiko Takagi on 02/13/2024 and stated in the office action mailed 03/25/2024.
Claims 19-20 are withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected invention, there being no allowable generic or linking claim. Election was made without traverse in the telephone conversation on 02/13/2024 as stated in the office action mailed 03/25/2024.
Claim Objections
Claim 11 is objected to for the phrases:
“a freezing step for freezing a starting material … wherein the starting material comprises raw cartilage … the raw cartilage … has not undergone freezing” in lines 3-4 and 6-8,
“…articles obtained in the freeze-drying step to carry out extraction at 14.5 °C or lower” in line 6, and
“a pH of the aqueous solvent is from 9 to 12” in line 10.
In the interest of improving claim form, Applicant should consider an amendment to recite phrases:
“a freezing step for freezing a starting material, wherein the starting material comprises raw cartilage derived from fish, and wherein the raw cartilage … has not undergone freezing prior to the freezing step”,
“…articles obtained in the freeze-drying step, wherein extraction is carried out at 14.5 °C or lower”, and
“wherein the aqueous solvent in the extraction step has a pH from 9 to 12”.
Claim Rejections - 35 USC § 103
The rejection of claims 11 and 13 under 35 U.S.C. 103 as being unpatentable over Hirosaki et al. (JP 2017-066097; cited on the IDS submitted 07/15/2021; herein referred to as Hirosaki; reference is made to a machine translation cited on the Form PTO-892 mailed 03/25/2024) and
the rejection of claims 12 and 14-18 under 35 U.S.C. 103 as being unpatentable over Hirosaki, and further in view of Eiyogaku et al. (JP 2003-024044; cited on the IDS submitted 07/15/2021; herein referred to as Eiyogaku; reference is made to a machine translation cited on the Form PTO-892 mailed 03/25/2024)
are withdrawn in view of the amendment to claim 11 to recite limitations regarding the temperature of the extraction step and the pH of aqueous solution used in the extraction step.
Claims 11, 13 and 21 are rejected under 35 U.S.C. 103 as being unpatentable over Hirosaki in view of Yanagishita et al. (Glycoconj J, 2009, 26:953; cited on the attached Form PTO-892; herein referred to as Yanagishita) and Vasquez et al. (Marine Drugs, 2018, 16:344; cited on the attached Form PTO-892; herein referred to as Vasquez).
The instant rejection is maintained from a previous office action, and any newly recited portions are necessitated by claim amendment.
Claims 11, 13 and 21 are drawn to a method for manufacturing a proteoglycan-containing composition comprising
a freezing step with raw cartilage as a starting material that has never been above 30 °C and has not previously been frozen,
a freeze-drying step for freeze-drying frozen articles obtained in the freezing step, and
an extraction step for extracting articles with an aqueous solvent from freeze-dried articles contained in the freeze-drying step to carry out extraction at 14.5 °C or lower,
wherein the starting material comprises raw cartilage derived from fish,
the raw cartilage has not had a history of reaching a temperature of 30 °C or higher and has not undergone freezing, and
a pH of the aqueous solvent is from 9 to 12.
Hirosaki discloses a method for preparing a cartilage water extract comprising proteoglycan [abstract].
Regarding claim 11, Hirosaki discloses a method for preparing a fish cartilage water extract [p 5, para 6], wherein proteoglycan is directly extracted from the cartilage collected from fish [p 5, para 8], and “extraction is performed using water ... after being refined (e.g., fragmented or powdered)” [p 5, para 7]. Hirosaki defines “powdered” as “refer[ring] to a smaller one than ‘small piece’, but is not intended to be clearly distinguished” and specifies that the powder size is not limited [p 5, para 14]. Hirosaki further discloses that samples can be powdered by freeze-drying or spray-drying [p 7, para 10]. One of skill in the art would understand that a sample which is freeze-dried would require the preceding step of freezing said sample. Furthermore, Hirosaki discloses the sample be frozen until used for extraction, and a known freezing method can be used [p 5, para 8].
Hirosaki does not teach the extraction step is carried out at 14.5 °C or lower, and the pH of the aqueous solvent is from 9 to 12.
Yanagishita relates to extraction and separation of proteoglycans [title], and discusses various techniques for separating proteoglycans from tissues or cells [abstract].
Regarding claim 11 and the limitations corresponding to extraction temperatures, Yanagishita discloses a method of extracting proteoglycan from tissue cell culture comprising incubating for 2-3 h at 4 °C [p 954, col 2, para 4].
Vasquez relates to the isolation of chondroitin sulfate (CS) from cartilage by-products of Blackmouth Catshark [title], and discusses methods of isolating the proteoglycan chondroitin sulfate using cartilage hydrolysis with alcalase to high purity [abstract].
Regarding claim 11 and the limitations corresponding to pH of the aqueous solution during extraction, Vasquez describes a method of CS purification where cartilage is digested by enzyme proteolysis at various pH and temperature [p 3, Section 2.1, and Table 1], and the resulting CS is measured as shown in [Figure 1, middle]. As Vasquez discloses the CS hydrolysates resulting from alcalase treatment were subjected to alkaline hydrolysis comprising adding NaOH to reach the pH shown in Table 1 [p 10, Section 3.4], the method of Vasquez is considered to correspond to the extraction of proteoglycan using an aqueous solvent, wherein the pH of the aqueous solvent corresponds to the pH ranges shown in Table 1 of 6.0 to 10.0. According to MPEP 2144.05, in the case where the claimed ranges overlap or lie inside ranges disclosed by the prior art, a prima facie case of obviousness exists. One of ordinary skill in the art would have been further motivated to use the extraction parameters of Vasquez because Vasquez shows in [Figure 1, middle] that while the optimum yield for CS appears to theoretically occur at a pH near 8 and a temperature near 55 °C, the extraction of CS is still favorable at higher pH from 8-10 with decreasing temperature.
In view of Hirosaki, it would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to obtain a frozen fish cartilage followed by making a freeze-dried powder of the fish cartilage and extracting proteoglycan from the freeze-dried powder of the fish cartilage. One of ordinary skill in the art would have been motivated to obtain a frozen fish cartilage followed by making a freeze-dried powder of the fish cartilage and extracting proteoglycan from the freeze-dried powder of the fish cartilage, because Hirosaki teaches the sample be frozen until used for extraction, Hirosaki teaches extraction is performed using water after being refined (e.g., fragmented or powdered), and that samples can be powdered by freeze-drying. One of ordinary skill in the art would have had a reasonable expectation of success because of the express teachings of Hirosaki as set forth above.
In view of the additional teachings of Yanagishita and Vasquez, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date to modify the method of Hirosaki by applying the teachings of Yanagishita and Vasquez regarding the temperature and pH of the extraction to arrive at the claimed invention. One of ordinary skill in the art would have been motivated to modify the method of Hirosaki, because Yanagishita teaches a method for isolating proteoglycans at 4 °C from tissue, and Vasquez teaches a method for extracting the proteoglycan CS at pH ranges of 6-10 and the associated efficiencies of each. One of skill in the art would have had a reasonable expectation of success because Hirosaki, Yanagishita and Vasquez all relate to the aqueous extraction of proteoglycan from tissue.
Regarding claim 13, Hirosaki discloses the component analysis of freeze-dried extract (FD), wherein the FD was subjected to atmospheric pressure heat drying [p 9, para 2], therein corresponding to the furthermore drying of extracted articles in the claim.
Regarding claim 21 and the limitations corresponding to extraction temperatures from 10.5 to 14.5 °C, Vasquez describes a method of CS purification where cartilage is digested by enzyme proteolysis at various pH and temperature [p 3, Section 2.1, and Table 1], and the resulting CS is measured as shown in [Figure 1, middle]. As Vasquez discloses the CS hydrolysates resulting from alcalase treatment were subjected to alkaline hydrolysis comprising adding NaOH to reach the pH shown in Table 1 [p 10, Section 3.4], the method of Vasquez is considered to correspond to the extraction of proteoglycan using an aqueous solvent. Vasquez shows in [Figure 1, middle] that while the optimum yield for CS appears to theoretically occur at a pH near 8 and a temperature near 55 °C, the extraction of CS is still favorable at higher pH from 8-10 with decreasing temperature.
While Hirosaki, Yanagishita and Vasquez do not explicitly teach a proteoglycan extraction between 10.5 °C – 14.5 °C, Yanagishita teaches a proteoglycan extraction at 4 °C, and Vasquez teaches a proteoglycan extraction with theoretically increasing yield as temperature increases to 55 °C as discussed above. According to MPEP 2144.05.II.A, where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation. Additionally, Vasquez identifies the result-effective variable, (a variable that achieves a recognized result according to MPEP 2144.05.II.B) of temperature, wherein increasing temperature up to a certain point is shown to increase proteoglycan yield [Figure 1, middle]. Therefore in view of the teachings of Yanagishita and Vasquez, one of skill in the art would have been able to achieve the claimed extraction temperature, as Yanagishita teaches an extraction at 4 °C and Vasquez establishes that increasing temperature can increase proteoglycan yield.
Therefore, the invention of claims 11, 13 and 21 would have been obvious to one of ordinary skill in the art before the effective filing date.
Claims 12 and 14-18 are newly rejected under 35 U.S.C. 103 as being unpatentable over Hirosaki, Yanagishita and Vasquez as applied to claims 11, 13 and 21 above, and further in view of Eiyogaku.
The instant rejection is newly stated and necessitated by claim amendment.
Claim 12 is drawn to the method of claim 11, wherein the starting material is frozen so as to reach the temperature band of -5 °C to less than 0 °C over 30 minutes or more. The instant specification refers to this process as “slow freezing” [p 13].
Claim 14 is drawn to the method of claim 13, wherein dried articles obtained in the drying step contain 37 mass% or more of proteoglycans and contain 36 mass$ or more of collagen.
Claim 15 is drawn to the method of claim 14, wherein the mass ratio of proteoglycans and collagen is 1:1.7 to 1.25:1.
Claim 16 is drawn to the method of claim 14, wherein the weight-average molecular weight of the proteoglycans is 2,000,000 to 4,150,000 Daltons.
Claim 17 is drawn to the method of claim 14, wherein a lipid content is 1 mass% or less.
Claim 18 is drawn to the method of claim 14, wherein proteoglycans having a weight-average molecular weight within the range of 2,000,000 to 3,400,000 Daltons occupy 30 mass% or more of the composition.
The teachings of Hirosaki, Yanagishita and Vasquez as applied to claims 11, 13 and 21 are discussed above. Hirosaki teaches the frozen storage of starting material, and that the freezing method is not particularly limited and any known freezing method could be used [p 5, para 8]. These references do not teach the process of freezing so as to reach the temperature band of -5 °C to less than 0 °C over 30 minutes or more, which is referred to as “slow freezing” in the instant specification [p 13].
Eiyogaku discusses methods for producing Chlorella whose cellular membranes are broken comprising the processes of slow freezing and vacuum-drying the frozen Chlorella [abstract], and describes said methods to efficiently destroy the extremely tough cell membranes and improve efficiency of digestion and absorption [paras 0001 and 0003].
Regarding claim 12, Eiyogaku teaches a slow freezing method of lowering the temperature from 1 to 6 °C per hour to freeze [claim 1]. Thus the method taught by Eiyogaku would reduce the temperature 1 °C per hour until freezing, and therefore would bring the sample to the temperature band recited in the claims for over 30 minutes. While the combined method of Hirosaki, Yanagishita and Vasquez and the method of Eiyogaku relate to different processes, both methods overlap regarding the process of freezing a material from which components are intended to be used, as Hirosaki discusses freezing starting cartilage material for the subsequent extraction of the component proteoglycan, and Eiyogaku discusses freezing cells for subsequent increased absorption and digestion of the internal components. As Hirosaki teaches that any known freezing method can be used, and Eiyogaku teaches a known freezing method characterized for increasing the efficiency of releasing internal components upon subsequent use, one of skill in the art would recognize that the slow freezing method of Eiyogaku can be applied to the combined method of Hirosaki, Yanagishita and Vasquez.
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the combined method of Hirosaki, Yanagishita and Vasquez by using the slow freezing technique of Eiyogaku to arrive at the claimed invention. One of ordinary skill in the art would have been motivated to modify the combined method of Hirosaki, Yanagishita and Vasquez by using the slow freezing technique of Eiyogaku, because Hirosaki teaches a method of extracting proteoglycan comprising freezing steps wherein any known freezing method could be used, and Eiyogaku teaches a known freezing method. One of ordinary skill in the art would have had a reasonable expectation of success because both Hirosaki and Eiyogaku teach methods of freezing and preparing freeze-dried products.
Regarding claims 14-15, Hirosaki teaches a method of preparing nasal cartilage (as discussed above in the rejection of claim 11), wherein the freeze-dried extract (FD) contained 31.89 g proteoglycan and 43.7 g collagen per 100 g sample [Table 2 of the translation], wherein g / 100 g sample is interpreted to be mass% recited in the claims. Hirosaki does not teach 36 mass% or more of proteoglycans and 36 mass% or more of collagen as recited in claims 14-15 and does not teach or suggest the mass ratio of the proteoglycans and the collagen being 1:1.7 to 1.25:1 as recited in claim 15. However, according to MPEP 2144.05.II.A, where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation. Hirosaki further teaches methods of tuning the yield based on differences in isolated molecular weight proteoglycans, such as the use of an acid compound or an alkali compound during extraction to reduce or eliminate high molecular weight proteoglycans, especially those exceeding 10,000,000 Da [p 6, para 6], therefore identifying result-effective variables, which are variables that achieve a recognized result according to MPEP 2144.05.II.B. Therefore in view of the results and teachings of Hirosaki, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the combined method of Hirosaki, Yanagishita, Vasquez and Eiyogaku to achieve the claimed mass% proteoglycan, mass% collagen, and mass ratio of proteoglycan:collagen, as Hirosaki establishes the result-effective variables of acidic and alkali compounds that effect the results of molecular weight range of extracted proteoglycans and therefore %proteoglycan and %collagen in extracted compositions.
Regarding claims 16 and 18, the results of FD analysis described in the rejection to claims 14-15 above teaches the 31.98 g proteoglycan per 100 g sample obtained [Table 2 of the translation of Hirosaki] has a molecular weight above 1,800,000 Da [p 9, para 9 and Table 2 of the translation of Hirosaki]. Hirosaki does not teach the weight average molecular weight of the proteoglycan is 2,000,000 to 4,150,000 Daltons as recited in claim 16 and wherein the proteoglycans having a weight average molecular weight within the range of 2,000,000 to 3,400,000 Daltons occupy 30 mass% or more of the composition. However, according to MPEP 2144.05.II.A, where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation. Hirosaki further teaches methods of tuning the yield based on differences in isolated molecular weight proteoglycans, such as the use of an acid compound or an alkali compound during extraction will reduce or eliminate high molecular weight proteoglycans, especially those exceeding 10,000,000 Da [p 6, para 6], therefore identifying result-effective variables which are variables that achieve a recognized result according to MPEP 2144.05.II.B. Therefore, in view of the results and teachings of Hirosaki, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the combined method of Hirosaki, Yanagishita, Vasquez and Eiyogaku to achieve the claimed weight average molecular weight of proteoglycan, as Hirosaki establishes the result-effective variables of acidic and alkali compounds that effect the results of molecular weight range of extracted proteoglycans in extracted compositions. Furthermore, Hirosaki establishes the range of proteoglycan molecular weight extracted as greater than 1,800,000 Da [p 9, para 9 and Table 2 of the translation] which encompasses the range of 2,000,000 to 4,150,000 Da recited in claim 16, and the range of 2,000,000 to 3,400,000 Da recited in claim 18, as according to MPEP 2144.05.I, “in the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’, a prima facie case of obviousness exists”.
Regarding claim 17, the results of FD analysis described in the rejection to claims 14-15 above describes the lipid content as 1 g per 100 g sample [Table 2 of the translation of Hirosaki].
Therefore, the invention of claims 12 and 14-18 would have been obvious to one of ordinary skill in the art before the effective filing date.
Response to Remarks: Beginning on page 5 of Applicant’s response to rejections under 35 USC 103; Applicant in summary contends that altering the method of Hirosaki to use an alkaline solvent of pH 9-12 would render the method of Hirosaki unsatisfactory for its purpose of isolating high molecular weight (HMW) proteoglycans (see MPEP 2143.01.V), as Hirosaki teaches the addition of alkali would cause HMW proteoglycan to decrease or disappear [para 0051], and that adding the alkali of Vasquez to the method of Hirosaki would destroy the product Hirosaki intends to recover. Applicants remarks are considered and found not convincing.
While Hirosaki indeed teaches the HMW of proteoglycans can be reduced or eliminated by addition of alkali, the purpose of Hirosaki is considered to be providing an oral composition comprising fish cartilage extract containing proteoglycan [abstract, and paragraph 1 of the Description section on p 1 of the machine translation]. Hirosaki states that in addition, the inventors have developed a technique for extracting HMW proteoglycan from fish [p 2, para 1 of the machine translation]. Therefore while the intention of Hirosaki is to provide a composition comprising an extract containing proteoglycan, Hirosaki additionally describes a method for extracting HMW proteoglycan. Therefore, the addition of the alkali of Vasquez to the method of Hirosaki would not render the method of Hirosaki unsatisfactory, as the combined method described in the rejection above would still produce an extract containing proteoglycan.
MPEP 2143.01.V states the proposed modification cannot render the prior art unsatisfactory for its intended purpose. Additionally, this section of MPEP emphasizes the importance of prior art in teaching away from a proposed modification that would result in an inoperable process with undesirable properties. While Hirosaki states that it is preferable not to add an alkali compound [p 6, para 5 of the machine translation], according to MPEP 2123.II, disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments. In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971). “A known or obvious composition does not become patentable simply because it has been described as somewhat inferior to some other product for the same use.” Therefore the preference to not use alkali does not constitute a teaching away from the use of alkali in the method of Hirosaki. Furthermore, there is no indication from Hirosaki that the use of alkali would render the method of extracting proteoglycan to be inoperable, and therefore one of skill in the art would expect the combined method proposed in the rejection to produce an extract containing proteoglycan.
Regarding the assertion that the alkali of Vasquez would destroy the HMW proteoglycan: the use of alkali as taught by Vasquez in the combined method set forth in the rejection above would not necessarily destroy all HMW proteoglycan, wherein HMW proteoglycan is defined as a molecular weight range of >1.8 million Da [claim 1] that can exceed 10 million Da [p 6, para 5 of the machine translation]. Hirosaki teaches the addition of alkali would cause the HMW to reduce or disappear as stated by Applicant. One of ordinary skill in the art in considering the teachings of Hirosaki would be expected to reason that treatment of HMW proteoglycan with alkali would reduce or destroy the HMW proteoglycan, but the degree of reduction or destruction would be dependent on many factors (e.g. pH, time, temperature). Therefore one of ordinary skill in the art would be expected to reason that the addition of alkali to HMW proteoglycan would result in at least a portion of the HMW proteoglycan reduced or destroyed as taught by Hirosaki, however not necessarily all of the HMW proteoglycan in the extract would be reduced or destroyed, and not all of the proteoglycan in the extract would be reduced or destroyed. In view of the interpretation that Hirosaki is not requiring the extract to contain HMW proteoglycan in view of the description in the abstract as stated above, the combined method set forth in the rejection would not be considered to destroy the product Hirosaki intends to recover.
Considering an alternative interpretation that the method of Hirosaki requires the extract to contain HMW proteoglycan, wherein the addition of alkali to increase pH of the extraction would render the intended purpose of Hirosaki inoperable and unsatisfactory, it is noted that claim 16 requires the weight-average molecular weight of the proteoglycan to be 2 million to 4.15 million Da (corresponding to Hirosaki’s definition of HMW proteoglycan as stated above), and claim 16 ultimately depends from claim 1 which as amended requires the extraction of proteoglycans in an aqueous solvent with pH of 9-12. Therefore, contrary to applicant’s position, the combined method of the rejection would not render the alleged intended purpose of extracting HMW proteoglycan inoperable.
Conclusion
Status of the Application:
Claims 11-21 are pending.
Claims 19-20 are withdrawn.
Claims 11-18 and 21 are rejected.
No claim is in condition for allowance.
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 nonprovisional extension fee (37 CFR 1.17(a)) 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 mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOSEPH SPANGLER whose telephone number is (571)270-0314. The examiner can normally be reached M-F 7:30 am - 4:30 pm.
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/JOSEPH R SPANGLER/
Examiner
Art Unit 1656
/David Steadman/Primary Examiner, Art Unit 1656
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