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 .
Status of the Claims
Claims 1-13 and 35-41 are pending (claim set as filed on 08/03/2026).
Applicant’s election with traverse of Group I directed to the composition is again acknowledged. Claims 35-40 stand withdrawn as being directed to the non-elected method claims. Therefore, only product/composition claims 1-13 and 41 are under examination.
Priority
This application is a 371 of PCT/JP2020/046426 filed on 12/11/2020, which has a foreign application to JP 2019-225959 filed on 12/13/2019.
Information Disclosure Statement
The Information Disclosure Statement (IDS) submitted on 08/11/2026 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.
Withdrawal of Rejections
The response and amendments filed on 08/03/2026 are acknowledged. Any previously applied minor objections and/or minor rejections (i.e., formal matters), not explicitly restated herein for brevity, have been withdrawn necessitated by Applicant’s formality corrections and/or amendments. For the purposes of clarity of the record, the reasons for the Examiner’s withdrawal, and/or maintaining if applicable, of the substantive or essential claim rejections are detailed directly below and/or in the Examiner’s response to arguments section.
The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Maintained Rejection
Claim Rejections - 35 USC §101, Subject Matter Eligibility
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1-13 and 41 are rejected under 35 U.S.C. 101 because they are drawn to ineligible subject matter.
Broadest reasonable interpretation (BRI) of base claim 1: the broadest scope of claim 1 is drawn to a composition comprising portion of a protein (i.e., a “fraction” or piece of protein from an immortalized megakaryocytes’ metabolites or products thereof). The phrase “of immortalized megakaryocytes that have finished releasing platelets, wherein the immortalized megakaryocytes each comprise an exogenous BMI1 gene, an exogenous MYC gene, and an exogenous Bcl-xL gene” does not impart a distinctive structural characteristic to the product of “a protein fraction”. The MPEP 2103(C) states that “Examiners should begin claim analysis by identifying and evaluating each claim limitation … For products, the claim limitations will define discrete physical structures or materials. Product claims are claims that are directed to either machines, manufactures or compositions of matter”. Thus, the emphasis for product/composition is primarily based upon definitive physical structure.
STEP 1: Is the claim directed to a process, machine, manufacture, or a composition of matter?
YES, the claims are directed to a composition of matter.
STEP 2A: PRONG ONE: Does the claim recite an abstract idea, law of nature, or natural phenomenon?
YES, the claims are considered to be “product of nature” exceptions (i.e., a mixture of naturally occurring products). The courts have held that “products of nature” fall under the laws of nature and/or natural phenomena exceptions.
PRONG TWO: Does the claim recite additional elements that integrate the judicial exception into a practical application?
NO, the additional elements or a combination of elements in the claims does not impose a meaningful limit on the judicial exception. Note that the markedly different characteristics analysis is used to determine if a nature-based product is a “product of nature” exception. Thus, the markedly different characteristics analysis is part of Step 2A, i.e., it helps answer the question of whether a claim is directed to an exception as further explained below.
STEP 2B: Does the claim recite additional elements that amount to significantly more than the judicial exception?
NO, the claimed invention is directed to a law of nature and/or natural phenomena (i.e., a product of nature) without significantly more. Note that the claims must be interpreted under the broadest reasonable interpretation (BRI) standard when evaluating for a marked difference. Under BRI, the claims broadly describe the cell’s natural metabolite, protein, cytokine, or growth factors thereof.
Applicant is claiming the resultant end product of a piece of protein from the cell (i.e., the protein fraction) and it does not matter if the source cell is non-natural, synthetically engineered, or artificially altered where “the analysis turns on whether the nature-based product in the claim has markedly different characteristics from its naturally occurring counterpart” (MPEP 2106.04(C)(I)(B)). Turning to the dependent claims which describes the protein fraction to be, e.g., bFGF, IGFBP-2, PIGF, SCFR, VEGF, et. al., these fractions are naturally occurring or at least resembles proteins found in nature as shown in the previously cited Burnouf prior art.
There is no indication that the claimed composition has any markedly different characteristic (e.g., structure, function, phenotype, etc.) that is different than what is found in nature. Thus, it appears that Applicant is claiming a naturally occurring product or one that substantially resembles a naturally occurring product.
Therefore, the claims are interpreted under the BRI standard, wherein the claim does not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claim does not recite any additional elements.
Therefore, the claims, as a whole, are considered as products of nature which are directed to judicially recognized exceptions without amounting to significantly more from what occurs in nature and thus, are not eligible subject matter under 35 U.S.C. §101.
Examiner’s Response to Arguments
Applicant’s amendments and arguments filed on 04/03/2026 have been fully considered but they are not persuasive and deemed insufficient to overcome the subject matter eligibility.
In response to Applicant’s argument (addressing pages 6-8 of the remarks) that the claimed combination of a protein fraction of immortalized megakaryocytes and bFGF in an amount of 2000 pg or more in 1 mg of a total protein thereof, as a whole, is not present in nature, and the composition of claim 1 is markedly different from the natural counterpart: this argument is not persuasive for the reasons of record. First note that Applicant is claiming the resultant end-product of a protein fraction so the description pertaining to how the immortalized megakaryocyte produces the protein fraction is a product-by-process limitation. In other words, the analysis is based upon the distinctive final product. Second, the amount or concentration of the protein fraction does not make the claim marked different even if the amount is not found in nature. Rather, the analysis turns to whether the claim is ‘markedly different’. The MPEP 2106.04(c) states that:
“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. Non-limiting examples of the types of characteristics considered by the courts when determining whether there is a marked difference include:
• Biological or pharmacological functions or activities;
• Chemical and physical properties;
• Phenotype, including functional and structural characteristics; and
• Structure and form, whether chemical, genetic or physical”.
In simple terms, merely because Applicant has more of something that is natural product does not make it different enough from its naturally occurring counterpart. Applicant would need to illustrate how the claimed product is markedly different in terms of biological properties, structure, or function from its naturally occurring counterpart. For example, Applicant may provide a structure of the claimed basic fibroblast growth factor (bFGF) and show the comparison of its structure versus bFGF that exist in nature to illustrate that it is different (i.e., a marked difference).
Claim Rejections - 35 USC § 102/103, Anticipation-Obviousness
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.
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 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 non-obviousness.
Claims 1-13 and 41 are rejected under 35 U.S.C. 102(a)(1) as being anticipated, or in the alternative under 35 U.S.C. 103, as being unpatentable over Eto (US 2018/0016597 A1).
Eto’s general disclosure relates to a method for efficiently polyploidizing megakaryocytes before polyploidization, a method for producing platelets from such megakaryocytes (see ¶ [0002]).
Eto discloses “immortalized megakaryocytic progenitor cell line is the one which is imparted with enhanced proliferative potential and is established (immortalized) by inducing expression of an oncogene such as MYC or a gene such as BMI1 in the megakaryocyte progenitor cells derived from pluripotent stem cells” (see ¶ [0021]-[0026]). Eto discloses the apoptosis suppressor gene is a BCL-XL gene and wherein the c-MYC gene is used as the oncogene (see ¶ [0027]-[0039]); and expression of an exogenous apoptosis suppressor gene (see ¶ [0154]). Eto teaches the blood cell composition is distributed in a frozen state (see ¶ [0142]).
Eto teaches a “method of producing platelets according to the present invention, on the other hand, produces platelets in vitro from the polyploidized megakaryocytes and the like obtained using the method of the present invention” (see ¶ [0146]-[0147]). Eto teaches culturing of immortalized megakaryocytes using a conditioned medium and the platelets contained in the supernatant of the medium were analyzed with a flow cytometer (see ¶ [0204]-[0209]).
Anticipation: the cited reference is silent with regards to “a protein fraction” or the amount but there is a reason to believe that said protein fraction is an inherent feature of said reference because Eto teaches the culturing of immortalized megakaryocytes that have released platelets wherein the immortalized megakaryocytes each comprise an exogenous BMI1 gene, MYC gene, or BCL-XL gene. The technical reasoning is because the instant application discloses the culturing of immortalized megakaryocytes where the protein is present in the supernatant as a protein fraction (see ¶ [0107]) and the prior art of Eto also discloses the culturing of immortalized megakaryocytes that have released platelets in the supernatant (see ¶ [0209]). Therefore, “a protein fraction” of immortalized megakaryocytes that have released platelets should be inherently contained in the supernatant portion of the culture conditioned medium.
Obviousness: in the alternative, if not expressly taught by the references with regards to the amount of protein fraction, the MPEP 2144.05(II) states that “Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. 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”. The adjustments of particular conventional working conditions (e.g., the amount or concentration) is deemed a matter of judicious selection and routine optimization which is within the purview of the skill artisan. Therefore, one of ordinary skill in the art would recognize that claimed amount or concentration of protein fraction is a result effective variable dependent upon the amount of starting material used. This is motivation for someone of ordinary skill in the art to practice or test the parameter widely to find those that are functional or optimal which then would be inclusive or cover the steps as instantly claimed. Absent any teaching of criticality by the Applicant concerning the amount, it would be prima facie obvious that one of ordinary skill in the art would recognize these limitations are result effective variable which can be met as a matter of routine optimization (MPEP 2144.05 II).
Thus, the claimed invention as a whole was at least prima facie obvious, if not anticipated by the reference, especially in the absence of an objective showing of surprising or unexpected results.
Claims 1-13 and 41 are rejected under 35 U.S.C. 102(a)(1) as being anticipated, or in the alternative under 35 U.S.C. 103, as being unpatentable over Hirose (US 2018/0282697 A1).
Hirose’s general disclosure relates to a method for producing purified platelets from a culture of megakaryocytes (see abstract & ¶ [0001]-[0006]).
Hirose teaches the method comprises centrifugal separation step and a liquid component is recovered and “wherein the culture of megakaryocytes is obtained by the steps of: overexpressing a cancer gene and a Polycomb gene in cells less differentiated than megakaryocytes; overexpressing a Bcl-xL gene in the cells; and terminating all the overexpression” (see ¶ [0009]-[0020], [0047]-[0054], [0076]-[0087] for the production of immortalized megakaryocytes). Hirose teaches culturing the megakaryocytes in a medium and platelets were produced and purified (see ¶ [0064]-[0065], [0113]-[0129])
Anticipation: the cited reference is silent with regards to “a protein fraction” but there is a reason to believe that said protein fraction is an inherent feature of said reference because Hirose teaches the culturing of immortalized megakaryocytes that have released platelets wherein the immortalized megakaryocytes each comprise an exogenous BMI1 gene, MYC gene, or BCL-XL gene. The technical reasoning is because the instant application discloses the culturing of immortalized megakaryocytes where the protein is present in the supernatant as a protein fraction (see ¶ [0107]) and the prior art of Hirose also discloses the culturing of immortalized megakaryocytes that have released platelets for recovery. Therefore, “a protein fraction” of immortalized megakaryocytes that have released platelets should be inherently contained in the liquid component of the culture conditioned medium.
Obviousness: in the alternative, if not expressly taught by the references with regards to the amount of protein fraction, the MPEP 2144.05(II) states that “Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. 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”. The adjustments of particular conventional working conditions (e.g., the amount or concentration) is deemed a matter of judicious selection and routine optimization which is within the purview of the skill artisan. Therefore, one of ordinary skill in the art would recognize that claimed amount or concentration of protein fraction is a result effective variable dependent upon the amount of starting material used. This is motivation for someone of ordinary skill in the art to practice or test the parameter widely to find those that are functional or optimal which then would be inclusive or cover the steps as instantly claimed. Absent any teaching of criticality by the Applicant concerning the amount, it would be prima facie obvious that one of ordinary skill in the art would recognize these limitations are result effective variable which can be met as a matter of routine optimization (MPEP 2144.05 II).
Thus, the claimed invention as a whole was at least prima facie obvious, if not anticipated by the reference, especially in the absence of an objective showing of surprising or unexpected results.
Claim interpretation: regarding claim 1’s recitation of the phrase “a protein fraction from a cell fraction … that have finished releasing plates”, the claimed invention, as a whole, is directed to a product or composition of matter. However, said phrase invokes the interpretation of a product-by-process limitation where the patentability of a product does not depend on its method of production (MPEP 2113(I)).
The use of 35 U.S.C. § 102 and §103 rejections for product-by-process claims has been approved by the courts. "[T]he lack of physical description in a product-by-process claim makes determination of the patentability of the claim more difficult, since in spite of the fact that the claim may recite only process limitations, it is the patentability of the product claimed and not of the recited process steps which must be established. We are therefore of the opinion that when the prior art discloses a product which reasonably appears to be either identical with or only slightly different than a product claimed in a product-by-process claim, a rejection based alternatively on either section 102 or section 103 of the statute is eminently fair and acceptable. As a practical matter, the Patent Office is not equipped to manufacture products by the myriad of processes put before it and then obtain prior art products and make physical comparisons therewith." In re Brown, 459 F.2d 531,535, 173 USPQ 685, 688 (CCPA 1972).
Examiner’s Response to Arguments
Applicant’s amendments and arguments filed on 08/03/2026 have been fully considered but they are not persuasive and deemed insufficient to overcome the prior arts of record.
In response to Applicant’s argument (addressing pages 8-9 of the remarks) that “Eto does not disclose that the protein fraction is that of immortalized megakaryocytes that have finished releasing platelets” as amended: this argument is not persuasive for the reasons of record. The claimed is directed to a product or composition but Applicant emphasizes on how the product was made. In other words, the way that the protein fraction is made is interpreted as a product-by-process limitation where patentability does not depend on its production methodology. The Patent Office is not equipped to manufacture products by the myriad of processes put before it and then obtain prior art products and make physical comparisons therewith.
Conclusion
No claims were allowed.
Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the date of this final action.
Correspondence Information
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/NGHI V NGUYEN/Primary Examiner, Art Unit 1653
