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 .
Claim status
In the reply filed 23 July 2026, Applicant has amended claim 1, cancelled claims 16-17 and withdrawn claims 18-22.
Therefore, 1-15 and 18-22 are pending.
Election/Restrictions
Applicants previously elected with traverse of Group 1, claims 1-15 drawn to a method for preparing a culture medium-derived component or a crystallized culture medium exhibiting a high level of biological stability or activity in the reply filed on 06 February 2026.
Applicant argues that the special technical feature linking the inventions of Groups I-III clearly does constitute a special technical feature, which provides a contribution over the cited art. This is not found persuasive because the examiner was able to provide art which satisfied the limitations of group I, thereby demonstrating that the special technical feature lacks novelty. Accordingly, a lack of unity still exists between the restricted groups
Claims 18-22 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Therefore, claims 1-15 are under current examination.
Priority
This application was filed 07/07/2023 and is a 371 application of PCT/KR2022 /000401, filed 01/10/2022 which claims foreign priority to KR 10-2021-0002725, filed 01/08/2021. Examiner acknowledged the certified translated copy of the KR 10-2021-0002725 filed 23 July 2026.
Thus, the earliest possible priority for the instant application is 01/08/2021.
Withdrawn Abstract Objections
Applicant has submitted amended abstract on 23 July 2026, and compliant with MPEP §608.01(b). Therefore, the objection to abstract is withdrawn.
Withdrawn of rejections
Applicant amends claim 1 to recite "adding a co-solvent containing DMSO and acetone to a culture medium obtained by culturing cartilage tissue-derived cells and collecting the medium to obtain a mixture," therefore, breadth of a claim 1 renders the written description requirement. Accordingly, the prior rejection of claims 1-12, 15 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112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement is withdrawn.
New 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 1-12, 15 are newly rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim contains subject matter that was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor, at the time the application was filed, had possession of the claimed invention.
Under the written description guidelines (see MPEP 2163), the Examiner is directed to determine whether one skilled in the art would recognize that the Applicant was in possession of the claimed invention as a whole at the time of filing. The following considerations are critical to this determination.
To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail so that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116. An original claim may lack written description support when (1) the claim defines the invention in functional language specifying a desired result but the disclosure fails to sufficiently identify how the function is performed or the result is achieved or (2) a broad genus claim is presented but the disclosure only describes a narrow species with no evidence that the genus is contemplated. See Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1349-50 (Fed. Cir. 2010) (en banc). The written description requirement is not necessarily met when the claim language appears in ipsis verbis in the specification. "Even if a claim is supported by the specification, the language of the specification, to the extent possible, must describe the claimed invention so that one skilled in the art can recognize what is claimed. The appearance of mere indistinct words in a specification or a claim, even an original claim, does not necessarily satisfy that requirement." Enzo Biochem, Inc. v. Gen-Probe, Inc., 323 F.3d 956, 968, 63 USPQ2d 1609, 1616 (Fed. Cir. 2002).
Accordingly, to satisfy the written description requirement, the specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1562-63, 19 USPQ2d 1111 (Fed. Cir. 1991). See also MPEP 2163.
REQUIREMENTS TO ESTABLISH ACTUAL REDUCTION TO PRACTICE
"In an interference proceeding, a party seeking to establish an actual reduction to practice must satisfy a two-prong test: (1) the party constructed an embodiment or performed a process that met every element of the interference count, and (2) the embodiment or process operated for its intended purpose." Eaton v. Evans, 204 F.3d 1094, 1097, 53 USPQ2d 1696, 1698 (Fed. Cir. 2000).
The same evidence sufficient for a constructive reduction to practice may be insufficient to establish an actual reduction to practice, which requires a showing of the invention in a physical or tangible form that shows every element of the count. Wetmore v. Quick, 536 F.2d 937, 942, 190 USPQ 223, 227 (CCPA 1976). For an actual reduction to practice, the invention must have been sufficiently tested to demonstrate that it will work for its intended purpose, but it need not be in a commercially satisfactory stage of development. See, e.g., Scott v. Finney, 34 F.3d 1058, 1062, 32 USPQ2d 1115, 1118-19 (Fed. Cir. 1994) (citing numerous cases wherein the character of the testing necessary to support an actual reduction to practice varied with the complexity of the invention and the problem it solved). If a device is so simple, and its purpose and efficacy so obvious, construction alone is sufficient to demonstrate workability. King Instrument Corp. v. Otari Corp., 767 F.2d 853, 860, 226 USPQ 402, 407 (Fed. Cir. 1985).
For additional cases pertaining to the requirements necessary to establish actual reduction to practice see DSL Dynamic Sciences, Ltd. v. Union Switch & Signal, Inc., 928 F.2d 1122, 1126, 18 USPQ2d 1152, 1155 (Fed. Cir. 1991) ("events occurring after an alleged actual reduction to practice can call into question whether reduction to practice has in fact occurred"); Fitzgerald v. Arbib, 268 F.2d 763, 765-66, 122 USPQ 530, 531-32 (CCPA 1959) ("the reduction to practice of a three-dimensional design invention requires the production of an article embodying that design" in "other than a mere drawing"); Birmingham v. Randall, 171 F.2d 957, 80 USPQ 371, 372 (CCPA 1948) (To establish an actual reduction to practice of an invention directed to a method of making a product, it is not enough to show that the method was performed. "[S]uch an invention is not reduced to practice until it is established that the product made by the process is satisfactory, and this may require successful testing of the product."). See MPEP 2138.05.
Claim 1 encompasses adding a co-solvent containing DMSO and acetone to a culture medium (e.g., supernatant) wherein the culture supernatant was obtained by culturing any stem cells.
Teachings of the Specification:
The specification discloses that the culture medium-derived component or crystallized culture medium obtained by applying the culture supernatant obtained by culturing chondrocytes to the Precipitation with Compressed Fluid Anti-solvent (PCA) drying process. This supernatant can exhibit a chondrocyte recovery effect and an osteoarthritis treatment effect ([0055] of US20240066069A1). However, specification doesn't have to disclose the culture supernatant obtained by culturing any stem cells.
Working examples of the specification:
The chondrocytes were cultured until the saturation of the chondrocytes reached 100%, and then, the medium was removed, and the chondrocytes were washed twice with phosphate buffer. Subsequently, the culture medium for chondrocytes, from which FBS was removed, was added to the chondrocytes again and incubated for 7 days, and a culture supernatant was obtained there from [0084]. Furthermore, Example 1-3 disclose the preparation of culture medium-derived component of chondrocytes using PCA drying [0085]. More specifically, the culture medium is obtained by culturing chondrocytes in a medium and collecting the medium [0083]. Therefore, SPEC discloses demonstrate the PCA process for Chondrocyte culture medium. However, specification does not disclose PCA process for culture supernatants was obtained by culturing genus of stem cells. Therefore, the specification fails to identify a culture supernatant was obtained by culturing a genus of stem cells.
However, the specification does not show or disclose the process to obtain the culture supernatant by culturing a genus of stem cells. Therefore, any embodiments of the specification that does not meet all the limitations of the claim are reduced to practice. Therefore, an actual reduction to practice of an invention directed to the DMSO, and acetone is mixed into a culture supernatant was obtained by culturing a genus of stem cells of instant method is not established at the time of filling and POSITA cannot predictably identify a culture supernatant that exercise the instant invention that was obtained by culturing a genus of stem cells. Accordingly, the successful testing of the method of the current invention is not shows reduced to practice, therefore, it is not established that the product is satisfactory. See MPEP 2163(I)-(II) and 2163.02.
MPEP § 2163, besides an actual reduction to practice, Applicant may prove possession of the claimed invention by a showing that the invention was “ready for patenting” such as by the disclosure of drawings or structural chemical formulas that show that the invention was complete, or by describing distinguishing identifying characteristics sufficient to show that the Applicant was in possession of the claimed invention. Further, as per MPEP § 2163, “[f]or some arts, there is an inverse correlation between the level of skill and knowledge in the art and the specificity of disclosure necessary to satisfy the written description requirement.”
State of the Art at the Time of Filing:
In the prior art, Hiroi et al. (US20190327959A1; published on Oct. 31, 2019; cited in PTO892; hereinafter “Hiroi”) provides a cryopreservation vessel which has a coating that is capable of inhibiting the adhesion of cells or proteins and is resistant not only to aqueous solvents but also to organic solvents (for example, cryoprotectants, in particular, dimethyl sulfoxide) (abstract of Hiroi). Furthermore, Hiroi teaches that the cell culture medium was prepared by adding 10 (v/v) % DMSO and 10% Fetal Bovine Serum (CORNING) to Dulbecco's Modified Eagle Medium (DMEM) (Waka Pure Chemical Industries, Ltd.) ([0249] of Hiroi) and allowed the cells to be stored at -80°C. without causing a significant change in cell count before and after the storage (Fig. 7) [0250]. Therefore, it is obvious that the cells to be stored at -80°C using specific culture medium (i.e., DMEM) and the prior art does not support identifying the generic culture medium for the cell or protein cryopreservation.
In a separate art, Mohanraj et al. (J Orthop Res. 2018 Jul 13;36(11):2901–2910; cited in PTO892) discloses that the Chondrocytes and mesenchymal stem cells (MSCs) share some overlapping growth factors, but they do not possess the exact same active ingredient (see abstract and Results ¶ of Mohanraj).
Therefore, it is obvious that prior art does not support identifying the appropriate method of precipitating a culture supernatant was obtained by culturing genus of stem cells in a pressure vessel adding instantly claimed co-solvent containing DMSO and acetone.
The quantity of experimentation needed to make or use the invention:
Applicants have claimed an invention directed to adding co-solvent containing DMSO and acetone to a culture supernatant was obtained by culturing a genus of stem cells, however, SPEC is only indicating the use of adding co-solvent containing DMSO, and acetone to a culture supernatant was obtained by culturing cartilage tissue-derived cells. The genus of a culture supernatant was obtained by culturing any stem cells as claimed cannot be predictably made or used by the ordinary artisan. Such random experimentation to identify a culture supernatant that is obtained by culturing any stem cells as embraced by instant claim is required undue experimentation. Furthermore, functionally defined genus claims can be inherently vulnerable to invalidity challenges for lack of written description support, especially in fields that are highly unpredictable, where it is difficult to establish a correlation between structure and function for the whole genus or to predict what would be covered by the functionally claimed genus.
See ABBVIE DEUTSCHLAND GMBH & 2 CO. v. JANSSEN BIOTECH, INC., Appeals from the United States District Court for the District of Massachusetts in Nos. 09-CV-11340-FDS, 10-CV-40003-FDS, and 10-CV-40004-FDS, Judge F. Dennis Saylor, IV. See also Ariad, 598 F.3d at 1351 ("[T]he level of detail required to satisfy the written description requirement varies depending on the nature and scope of the claims and on the complexity and predictability of the relevant technology.”); see also Centocor Ortho Biotech, Inc. v. Abbott Labs., 636 F.3d 1341, 1352 (Fed. Cir. 2011) (noting the technical challenges in developing fully human antibodies of a known human protein).
Conclusion:
With these additional evidence, the culture medium-derived component or crystallized by adding instantly claimed co-solvent containing DMSO and acetone, wherein the culture supernatant obtained by culturing any stem cells is not well established at the time of filling and the ordinary artisan cannot predictably identify culture supernatant obtained by culturing any stem cells and one of skill in the art would neither expect nor predict the appropriate method to obtain the culture supernatant by culturing any stem cells.
Therefore, it concludes that the claimed co-solvent solvent containing DMSO and acetone into culture supernatant that obtained by culturing the genus of stem cells for preparing a culture medium-derived component or a crystallized culture medium doesn't have an adequate written description. It concludes that a skilled artisan would find the specification inadequately described. Therefore, the Applicant did not sufficiently possess the broader invention as claimed.
RESPONSE TO ARGUMENTS
Applicants’ arguments filed on 23 July 2026 are acknowledged.
Applicant argues that the co-solvent PCA process mechanism has sufficient predictability for a person of ordinary skill in the art based on the working examples such as examples 1-3. Cell secretions (Secretome) secreted by cartilage tissue-derived cells, chondrocytes, and stem cells (mesenchymal stem cells) commonly contain proteinaceous active ingredients such as growth factors, extracellular matrix (ECM), extracellular vehicles (EVs), and cytokines. Applicant further argues that culture media of cartilage tissue-derived cells and stem cells share physicochemical/biological secretion profiles similar to those of chondrocyte culture medium, one of ordinary skill in the art (POSITA) can sufficiently predict that the co-solvent PCA drying technology of the subject matter of the present claims can be applied in the same manner without undue experimentation to obtain high biological activity and yield. See remark pp. 7-8.
The Applicant's arguments have been fully considered but is not persuasive. The present rejection is directed to whether the amended claim scope is adequately supported by the original discloser so as to satisfy the written description requirement of 35 USC § 112(a). The relevant inquiry is whether the application as originally filed reasonably conveys to POSITA was in possession of the presently claims genus, including use of the co-solvent solvent containing DMSO and acetone into culture supernatant that obtained by culturing the genus of stem cells for preparing a culture medium-derived component or a crystallized culture medium.
MPEP 2164.08 states that the Federal Circuit has repeatedly held that "the specification must teach those skilled in the art how to make and use the full scope of the claimed invention without ‘undue experimentation’." In re Wright, 999 F.2d 1557, 1561, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993). See also In re Wright, 999 F.2d 1557, 1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993) (The evidence did not show that a skilled artisan would have been able to carry out the steps required to practice the full scope of claims which encompass "any and all live, non-pathogenic vaccines, and processes for making such vaccines, which elicit immunoprotective activity in any animal toward any RNA virus." (original emphasis)); In re Goodman, 11 F.3d 1046, 1052, 29 USPQ2d 2010, 2015 (Fed. Cir. 1993) (The specification did not enable the broad scope of the claims for producing mammalian peptides in plant cells because the specification contained only an example of producing gamma-interferon in a dicot species, and there was evidence that extensive experimentation would have been required for encoding mammalian peptide into a monocot plant at the time of filing).
In the instant specification, the working examples relied upon by applicants appear to demonstrate the PCA process for Chondrocyte culture medium. However, the amended claims encompass culture supernatant derived from a broader genus of stem cells. The original discloser does not appear to provide a representative number of stem cells derived culture supernatants across the claimed genus, nor does it identify common structural, physiochemical or biological characteristics sufficient to establish that the inventor possessed application of the claimed DMSO/acetone PCA process across genus.
Applicant argues that cartilage tissue-derived cells and mesenchymal stem cells produce secretome containing generally similar proteinaceous active ingredients such as growth factors, extracellular matrix (ECM), extracellular vehicles (EVs), and cytokines. However, similarity at the level of broad classes of secreted components does not, by itself, establish possession of the full claim genus. Mohanraj et al. indicates that the chondrocytes and mesenchymal stem cells (MSCs) share some overlapping growth factors, but they do not possess the exact same active ingredient (see abstract and Results ¶ of Mohanraj). Thus, the evidence does not establish that the disclosed chondrocyte culture-medium embodiments are representative of the full variety of stem-cell-derived culture media encompassed by the amended claims.
Accordingly, the original disclosure does not reasonably convey to POSITA that applicant was in possession at the time of filling of the presently claimed scope encompassing application of the recited DMSO/acetone co-solvent PCA process to culture supernatants obtained from the recites genus of stem cells. The new rejection under 35 USC § 112(a) for the lack of adequate written description is therefore maintained.
Maintained Claim Rejections - 35 USC § 103
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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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 is 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, 4, 7-12, and 14-15 are rejected under 35 U.S.C. 103 as being unpatentable over Lee et al. (KR20200106779, published on 09/15/2020; attached STIC MT copy; cited in IDS filed 07/07/2023; hereinafter “Lee’779”), in view of Lee et al., (US20220177828A1, Priority Data of Foreign Application KR1020190025421: Mar. 5, 2019; cited in PTO892; hereinafter “Lee’828”). This rejection is maintained for reasons of record and further explained below.
Regarding claims 1, 7-12, and 14-15, Lee’779 discloses a crystallization method of the culture medium solution using a precipitation with a compressed anti-solvent (PCA) process [0012], comprising the steps of: supplying a culture solution to a container and supplying, to the container, DMSO that is a third solvent; and adding a compressed anti-solvent (i.e., Carbon dioxide ([0015], [0025] of Lee’779) to the container, wherein the temperature and pressure of the container are obtained by being adjusted to 0-40 °C and 35-500 bar, respectively (see the abstract, paragraphs [0001] and [0012]-[0020], and claims 1-10 of Lee’779; STIC MT attached copy). Furthermore, Lee’779 discloses the crystallization method may be used to dry a stem cell culture solution including a protein (e.g., target protein evaluated by VEGF) that is sensitive to temperature and maintains a microstructure through crystallization ([0007] of Lee’779). Therefore, the multi-component mixture, and the cell culture solution are precipitated (crystalized) with co-solvent (claim 4, [0031], [0022] of Lee’779).
Although Lee’779 does not disclose the co-solvent contain acetone, however, such was known in the prior art.
Regarding claims 1 and 4, Lee’828 discloses a method for crystallization and supercritical drying of culture solution to obtain target material by drying a culture solution containing a first solvent and the target material dissolved in the first solvent comprises crystallizing the target material by replacing the first solvent with a second solvent (i.e., acetone) in the culture solution, and changing a phase of the second solvent to a supercritical phase (abstract, [0029] of Lee’828). The method of Lee’828 farther comprise vaporizing the second solvent in the supercritical phase and carried out at a temperature of 0-40° C. and a pressure of 35-500 bar ([0031]-[0032] of Lee’828). Furthermore, Lee’828 teaches that in the liquid phase step, a mixture of CO2 and EtOH substitutes water to crystallize the material dissolved in the culture solution ([0047] of Lee’828).
MPEP 2143 (A) states that combining prior art elements according to known methods to yield predictable results. The rationale to support a conclusion that the claim would have been obvious is that all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results to one of ordinary skill in the art. KSR, 550 U.S. at 416, 82 USPQ2d at 1395. Accordingly, it would have been obvious to practice the crystallization method of the culture medium solution of Lee’779 and include acetone and alcohol in the culture medium as taught by Lee’828 with a reasonable expectation of success. The POSITA would have been motivated at the time of filing to do so as taught by Lee’828 because crystallization and supercritical drying of the culture solution of Lee’828 can dry the culture solution while preventing the structural stability and activity of the target material ( dried material) dissolved in the culture solution from being denatured ([0085] of Lee’828).The POSITA would have had a reasonable expectation of success in combining the teachings of Lee’779 and Lee’828 because each of these teachings both successfully generated the crystallization and supercritical drying of the culture solution. Therefore, the products and methods taught by Lee’779 et al. in view of Lee’828 et al. would have been prima facie obvious over the products and method of the instant application. In regard to the reasonable expectation of success in doing so, include the Acetone and ethanol of Lee’828 had a reasonable expectation of success since the steps thereof required no more than pipetting the appropriate DMSO and acetone in a ratio and Ethanol v/v concentration and freeze-drying technology.
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
RESPONSE TO ARGUMENTS
Applicants’ arguments filed on 23 July 2026 are acknowledged.
Applicant argues that D2 (Lee’828) reference relates to a method of obtaining a target substance by crystallizing and supercritical drying a culture solution containing the target substance dissolved in a first solvent. Further, argues that D2 processed replacing the first solvent (water) in the culture solution with acetone as the second solvent to crystallize the target substance and then changing the phase of acetone to a supercritical phase to vaporize it. D2 teaches "direct replacement" with a solvent such as acetone or ethanol to remove moisture. Therefore, Since D2 has no teaching or benefit of mixing the two solvents, combining Dl and D2 to consider the binary co-solvent obvious would be considered hindsight. See remark pp. 9-10.
The Applicant's arguments have been fully considered but is not persuasive.
In response to Applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
Under the broadest reasonable claim interpretation of instant claims encompasses application of co-solvent system comprising DMSO and acetone in a PCA process to culture supernatants obtained from the recited cells. MPEP 2145 teaches, "It is well-established that a determination of obviousness based on teachings from multiple references does not require an actual, physical substitution of elements." In re Mouttet, 686 F.3d 1322, 1332, 103 USPQ2d 1219, 1226 (Fed. Cir. 2012). Likewise, the test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981).
In Lee’779, the primary reference teaches a crystallization method of the culture medium solution using a precipitation with a compressed anti-solvent (PCA) process. Specifically, Lee’779 discloses supplying the culture solution to a container and DMSO to the container and introducing a compressed anti-solvent (i.e., Carbon dioxide) to precipitated or crystalize components of the culture solution. See claim 4, [0012]. [0015], [0031], [0022] of Lee’779).
in the secondary reference, Lee’828 discloses a method for crystallization and supercritical drying of culture solution to obtain target material by drying a culture solution containing a first solvent and the target material dissolved in the first solvent comprises crystallizing the target material by replacing the first solvent with a second solvent (i.e., acetone) in the culture solution, and changing a phase of the second solvent to a supercritical phase (abstract, [0029] of Lee’828).
Accordingly, rejection does not rely on bodily incorporating the entire solvent-replacement process of Lee’828 into PCA process of Lee’779. Rather, Lee’779 establishes the use of DMSO in PCA crystallization process of culture solutions, while Lee’828 establishes acetone as a suitable solvent for processing and crystallizing target materials from culture solutions. Considering these teaching together, POSITA would have been motivated to employ acetone in conjunction with the DMSO-containing PCA process of Lee’779 as part of the solvent system used to process the culture supernatant.
POSITA would also have had a reasonable expectation of success on making such modification because both references teach the use of known solvents in culture-solution processing for precipitation, crystallization, solvent exchange and /or drying the target materials. The proposed combination therefore represents the predictable use of known solvent components according to their established functions rather than an impermissible hindsight reconstruction. Therefore, the claimed binary co-solvent limitation does not render the claimed subject matter nonobvious, and the rejection under 35 USC § 103 is maintained.
Applicants argue fundamental disconnect in PCA precipitation versus supercritical solvent replacement drying and the difference between 'solvent replacement' and 'binary co-solvent' leads to lack of motivation for combination. Simple substitution versus co-solvent combination is clearly technically different. If one of ordinary skill in the art would attempt to combine Dl and D2, he or she would try to "replace" DMSO of D1 with acetone of D2, and there is no reason or motivation at all to deliberately "mix DMSO and acetone, which have completely different chemical properties, into one co-solvent system. See remark pp. 10-11.
Applicant arguments regarding the alleged differences between PCA precipitation versus supercritical solvent replacement drying, the asserted denaturing effect of acetone, and the alleged lack of motivation to form a DMSO/acetone co-solvent have been fully considered but are not persuasive. Lee’779 teaches use of DMSO in a PCA process for crystallizing components from culture solutions, while Lee’828 teaches acetone as suitable solvent for processing and crystallizing target materials from culture solutions. The obvious inquiry does not require bodily incorporation of Lee’828’s entire supercritical-drying process into Lee’779 but rather considers what the combined teaching would have suggested to a POSITA. Taking together, the references would have suggested employing acetone in the solvent system of Lee’779 with a reasonable expectation of success. Applicant has not established that the proposed combination would have been technically inoperative or that any alleged superior biological activity or yield is unexpected relative to the closet prior art. Accordingly, the arguments do not overcome the prima facie case of obviousness and the rejection under 35 USC § 103 is maintained.
Subject Matter Free of Art
Current application claimed a method for preparing a culture medium-derived component or a crystallized culture medium exhibiting a high level of biological stability or activity, comprising: (a) adding a co-solvent containing DMSO and acetone to a culture medium to obtain a mixture; (b) adding a compressed anti-solvent (CO2) to the mixture obtained above. Dependent claims 2-3, 5-6 requires the DMSO and acetone ratio in the solvent and the co-solvent and the culture medium ratio. Furthermore, claim 13, limits the claim scope of the culture medium that obtained by culturing chondrocytes in a medium and collecting the medium.
The prior teachings of Lee’779 and Lee’828 successfully generated the crystallization and supercritical drying of the culture solution. Therefore, the method as taught by Lee’779 et al. in view of Lee’828 et al. would have been prima facie obvious over the method of the instant application. However, Lee’779 or Lee’828 does not teach or fairly suggest preparing the DMSO and acetone ratio in the solvent and the co-solvent and the culture medium ratio as claimed in claims 2-3 and 5-6. More specifically prior art does not teach claim scope of the culture medium that obtained by culturing chondrocytes in a medium and collecting the medium.
However, claims 2-3, 5-6 and 13 are objected to as being dependent upon a rejected base claim 1, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Conclusion
Applicants’ amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicants are reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the date of this final action.
No claims are allowed.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MASUDUR RAHMAN whose telephone number is (571)272-0196. The examiner can normally be reached M-F 8-5 (EST).
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Christopher Babic, can be reached on (571) 272-8507. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/MASUDUR RAHMAN/ Patent Examiner, Art Unit 1633
/JEREMY C FLINDERS/ Primary Examiner, Art Unit 1684
Prosecution Insights