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 .
Priority
The instant application is a national stage entry of PCT application PCT/PL2021/050051, filed 12/22/2023 under 35 USC 371.
Election/Restrictions
Applicant's election with traverse of group I, claims 1-6, 13 and 16-20, drawn to an isolated pancreatic islet storage medium, in the reply filed on 06/08/2026 is acknowledged. The traversal is on the grounds that: 1) both groups are unified by the same technical feature; 2) the cited reasoning for breaking the unity relies on combining references (MacDonald and Wszola) in a manner more appropriate for a full §103 rejection than during a restriction determination; 3) the claimed storage medium and its use are inseparable in practical application; and 4) the specification describes conditions under which the claimed storage medium is employed (Remarks, p5-8).
Applicant’s argument is not found persuasive because: As stated in Restriction Requirement mailed 04/08/2026, though the groups I and II share a technical feature, this technical feature is not a special technical feature as it does not make a contribution over the prior art over MacDonald et al. in view of Wszola et al.. MPEP § 1850 II states that “[W]hether or not any particular technical feature makes a "contribution" over the prior art, and therefore constitutes a "special technical feature," should be considered with respect to novelty and inventive step”. Therefore breaking the unity relies on combining references is appropriate. Moreover, the only consideration regarding the unity of invention is whether the inventions share a special technical feature, thus the listed reasons 3) and 4) are not included for consideration.
The requirement is still deemed proper and is therefore made FINAL. Accordingly, claims 1-6, 13, 16-20 and new added claims 23-24 (depended upon claim 1) are pending and under current examination.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code (p10, line 10). Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Claim Objections
Claims 1 and 16 are objected to because of the following informalities:
1) Claim 1 recites “comprising the following proteins” in line 3. To enhance the clarity of claim language, a conjunction “and” needs to be placed before the last alternative.
2) Claim 16 recites “decellurized ECM” should be “decellularized ECM”.
Appropriate correction is required.
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 1-6, 13, 16-20 and 23-24 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.
Claims 1 and 16 recite “(a) medium based on a commercial medium CMRL 1066 or RPMI”, the phrase “based on” renders instant claims indefinite. It is not clear how closely the medium may resemble the commercial medium and what factors are included or excluded from the commercial medium, therefore the metes and bounds are not clear.
Claims 2-6, 13 and 23-24 depend from claim 1, and claims 17-20 depend from claim 16, thus inherit the deficiency and are rejected on the same basis.
The terms “high” and “low” in claim 5 is a relative term which renders the claim indefinite. The terms “high” and “low” 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. In instant case, it is not clear what molecular weight is considered as “a high molecular weight” and what molecular weight is considered as “a low molecular weight” while distinguishing from different types of hyaluronic acid.
The term “preferably” in claims 4, 13 and 20 is a relative term which renders the claim indefinite. The term "preferably" renders the claims indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 4 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 3, which instant claim 4 depends from, recites a specific amount of each component in the culture medium (i.e., laminin with an amount of 84.3 mg/L). However, claim 4 limits the concentration (of stock solution) of each component, but set a range of the volume for each component in the medium, therefore fail to further limit the limitation set forth in claim 3.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Interpretation
Claims 1 and 16 recite the phrase “an isolated pancreatic islet storage medium”, which is interpreted as a medium for the storage of isolated pancreatic islet, it is an intended use. The purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction. See MPEP 2111.02.
Claims 1 and 16 are indefinite by reciting “(a) medium based on a commercial medium CMRL 1066 or RPMI”. For the purposes of compacted prosecution, the claims are interpreted as the medium base being commercial medium CMRL 1066 or RPMI.
Instant claim 4 recites “wherein laminin at a concentration of 1 mg/mL, hyaluronic acid at a concentration of 5 mg/mL, collagen I at a concentration of 1 mg/mL, and collagen IV at a concentration of 1 mg/mL are added to the medium”, which refers to the concentration of the stock solution of each component, is not a limitation further limit the structure and/or components of the medium of claim 3 and claim 1.
Instant claims 4, 13 and 20 are indefinite by reciting “preferably”, in giving the claims their broadest reasonable interpretation, the examiner has interpreted the limitation as not required for the claimed invention.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 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.
Claims 1-6, 16-19 and 23-24 are rejected under 35 U.S.C. 103 as being unpatentable over MacDonald et al. (J Biol Chem. 2011 May 27;286(21):18383-96) in view of Wszola et al. (EP3769796 A1, as cited in IDS).
MacDonald et al. teach differences between human and rodent pancreatic islets including the enzyme activity, protein level, and relative mRNA level (see Abstract).
Regarding claim 1, MacDonald et al. teach pancreatic islets were maintained from 2 to 24 h in the medium in CMRL 1066 tissue culture medium (see p18385, left column). This teaching reads on an isolated pancreatic islet storage medium comprising a commercial medium CMRL 1066. MacDonald et al. do not teach the medium comprises an additive of extracellular matrix (ECM) proteins. However, this was disclosed by Wszola et al..
Wszola et al. teach a detergent-free decellularized ECM preparation method, a detergent-free decellularized ECM in a powder form and in a liquid form (Abstract).
Regarding claim 1, Wszola et al. teach the presence of ECMs in Bioink for bioprinting is considered beneficial for recreation of a microenvironment with cell-cell connections (parag 0002). The primary bioink comprises at least one additive selected from: hyaluronic acid at a concentration of 0.001 to 0.100 mg/mL of the bioink, laminin at a concentration of 0.005 to 0.100 mg/mL of the bioink, collagen I at a concentration of 0.001 to 0.100 mg/mL of the bioink, collagen IV at a concentration of 0.005 to 0.175 mg/mL of the bioink (parag 0023). Herein the concentration of hyaluronic acid (1-100 mg/L), laminin (5-100 mg/L), collagen I (1-100 mg/L) and collagen IV (5-175 mg/L) overlap with the concentration of instant invention. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05(I).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify MacDonald et al.’s storage medium comprising CMRL 1066 , and add an additive of ECM proteins as taught by Wszola et al.. The skilled artisan would have been motivated to add the additive of ECM protein since Wszola et al. teach the presence of additive of ECM protein is considered beneficial for recreation of a microenvironment with cell-cell connections (parag 0002), which will be expected to achieve better cell condition for the pancreatic islet storage. There would be a reasonable expectation of success of adding an additive of ECM proteins since Wszola et al. teach the components and the concentration of the additive of ECM proteins (see i.e., parag 0023).
Regarding claim 2, as discussed above, MacDonald et al. teach pancreatic islets were maintained from 2 to 24 h in the medium in CMRL 1066 tissue culture medium (see p18385, left column).
Regarding claims 3 and 4, MacDonald et al. do not teach the additive of ECM proteins comprises laminin in an amount of 84.3 mg/L of medium, hyaluronic acid in an amount of 6.7 mg/L of medium, collagen I in an amount of 40.7 mg/L of medium, and collagen IV in an amount of 122.3 mg/L of medium. However, Wszola et al. teach hyaluronic acid at a concentration of 0.001 to 0.100 mg/mL of the bioink, laminin at a concentration of 0.005 to 0.100 mg/mL of the bioink, collagen I at a concentration of 0.001 to 0.100 mg/mL of the bioink, collagen IV at a concentration of 0.005 to 0.175 mg/mL of the bioink (parag 0023). Herein Wszola et al. teach the concentration of hyaluronic acid (1-100 mg/L), laminin (5-100 mg/L), collagen I (1-100 mg/L) and collagen IV (5-175 mg/L). In situations where the claimed range lies inside the range disclosed by the prior art a prima facie case of obviousness exists. See MPEP 2144.05(I). Moreover, it is not inventive to find optimal workable ranges by routine experimentation. See Jn re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
Regarding claim 5, Wszola et al. teach two types of hyaluronic acid: high molecular weight or low molecular weight, which were added to the culture medium and the islets were incubated therein for 48 h [Fig. 9]. In both the high (H) and low (L) molecular weight hyaluronic acid variants, pancreatic islets were functional at a level comparable to that of islets untreated with any supplements (parag 0110).
Regarding claim 6, MacDonald et al. each most of the human islet samples were maintained for 2–4 or 24 h in tissue culture medium (usually CMRL medium or PIM medium (which each contain 5 mM glucose)) after they were received (p18387, right column).
Regarding claims 16 and 18, MacDonald et al. teach pancreatic islets were maintained from 2 to 24 h in the medium in CMRL 1066 tissue culture medium (see p18385, left column). This teaching reads on an isolated pancreatic islet storage medium comprising a commercial medium CMRL 1066. MacDonald et al. do not teach the medium comprises an additive of extracellular matrix (ECM) proteins in form of a detergent-free decellularized ECM (dECM) solution in an amount of 1% to 2.5% by volume of the medium. However, Wszola et al. teach detergent-free decellularized extracellular matrix (dECM) (parag 0012), which can support cellular adhesion and maintenance of cell functions (parag 0010). In addition, Wszola et al. teach method of preparation of a primary bioink, which comprising 1%-10% (w/v) of the detergent-free decellurized ECM (dECM) solution (parag 0017). The range of 1% -2.5% lies inside of 1%-10%. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP 2144.05(I).
Regarding claim 17, Wszola et al. teach a detergent-free decellularized extracellular matrix (dECM) preparation method comprising mechanical fragmentation, preferably by mechanical extrusion, of an organ of animal origin (parag 0012).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify MacDonald et al.’s storage medium comprising CMRL 1066 , and add a detergent-free decellularized ECM (dECM) as taught by Wszola et al.. The skilled artisan would have been motivated to add the detergent-free dECM since Wszola et al. teach it can support cellular adhesion and maintenance of cell functions (parag 0010) and the absence of the detergent in dECM substantially affects the quality of the dECM obtained (parag 0011), which will be expected to achieve better cell condition for the pancreatic islet storage. There would be a reasonable expectation of success of adding a detergent-free decellularized ECM (dECM) since Wszola et al. teach the method of preparing the dECM (see i.e., parag 0012).
Regarding claim 19, MacDonald et al. each most of the human islet samples were maintained for 2–4 or 24 h in tissue culture medium (usually CMRL medium or PIM medium (which each contain 5 mM glucose)) after they were received (p18387, right column).
Regarding claims 23-24, it is noted that instant claims are directed to a medium of claim 1, the temperature of storing the isolated pancreatic islets (as recited in claim 23), as well as the whether or not treating isolated pancreatic islets prior to placement in the medium does not further limit the structure or components of the medium. As such, claims 23-24 are rejected for the same reason as claim 1.
Claims 1-6, 13, 16-20 and 23-24 are rejected under 35 U.S.C. 103 as being unpatentable over MacDonald et al. (J Biol Chem. 2011 May 27;286(21):18383-96) in view of Wszola et al. (EP3769796 A1, as cited in IDS), as applied to 1-6, 16-19 and 23-24 above, further in view of Haga et al. (Fukushima J Med Sci. 2021 Apr 10;67(1):17-26).
The teaching of MacDonald et al. and Wszola et al. is set forth above.
Regarding claims 13 and 20, MacDonald et al. teach the medium comprises glucose (p18387, right column), but do not teach the medium further comprises L-glutamine, Penicillin- streptomycin, amphotericin B and FBS. However, this was disclosed by Haga et al. at the time of instant invention.
Haga et al. investigated the effects of islet culture on graft survival and the changes in the biological characteristics of islets during preculture (p18, left column).
Regarding claims 13 and 20, Haga et al. teach the islets were cultured in complete medium (RPMI 1640 with 10 mM 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES), 2 mM L-glutamine, 100 U/mL penicillin, 100 mg/mL streptomycin sulfate, and 0.5 mg/mL amphotericin B supplemented with 10% fetal bovine serum (FBS) at 37°C in a humidified atmosphere containing 5% CO2 and 95% air (p18, right column).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify MacDonald et al.’s storage medium comprising CMRL 1066 , add an additive of ECM proteins as taught by Wszola et al., and further add L-glutamine, Penicillin- streptomycin, amphotericin B and FBS as taught by Haga et al.. The only difference between instant claim and MacDonald et al.’s in view of Wszola et al.’s medium comprising CMRL 1066 and additive of ECM proteins is the medium of instant claims further comprises L-glutamine, Penicillin- streptomycin, amphotericin B and FBS. Given that Haga et al. teach this is complete medium that islets can be cultured/stored in, one of ordinary skill in the art would have substitute MacDonald et al.’s in view of Wszola et al.’s medium comprising CMRL 1066 and additive of ECM proteins, and further add L-glutamine, Penicillin- streptomycin, amphotericin B and FBS in the medium for the culture/storage of islets depends on their preference. This simple substitution of one known element (medium comprising CMRL 1066 and additive of ECM proteins, and further add L-glutamine, Penicillin- streptomycin, amphotericin B and FBS in the medium) for another known element medium comprising CMRL 1066 and additive of ECM proteins) is likely to be obvious when predictable results are achieved. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, USPQ2d 1385, 1395 — 97 (2007) (see MPEP § 2143, B.
Conclusion
No claims are allowed.
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/Q.G./Examiner, Art Unit 1633
/FEREYDOUN G SAJJADI/Supervisory Patent Examiner, Art Unit 1699
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