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
This application is a 371 of PCT/KR2022/005913 filed on 04/26/2022, which has foreign applications to: KR 10-2022-0051044 filed on 04/25/2022, and KR 10-2021-0059516 filed on 05/07/2021.
Status of the Claims
Claims 8-23 are pending (claim set as filed on 04/28/2026).
Election/Restrictions
Newly submitted claims 16-23 are directed to an invention that is independent or distinct from the invention originally claimed for the following reasons: new claims 16-23 are drawn to a different statutory category of invention (processes or methods of using) from the originally examined claims which were drawn to products (i.e., compositions of matter). The examination analysis for products versus methods is vastly different wherein “For processes, the claim limitations will define steps or acts to be performed. For products, the claim limitations will define discrete physical structures or materials” (MPEP 2103(I)(C)). Moreover, the products as claimed can be used in a materially different process (as noted in their preambles and treatment of different disease states such as bone disease or estrogen deficiency). Alternatively, the product group versus method group lacks unity of invention because the common technical feature of mesenchymal stem cells having enhanced osteogenic differentiation is already taught in the prior art as explained below. Thus, the common technical feature among the groups is not considered to be a special technical feature as it does not make a contribution over the cited prior art below.
Since Applicant has received an action on the merits for the originally presented invention, this invention has been constructively elected by original presentation for prosecution on the merits. Accordingly, claims 16-23 are withdrawn from consideration as being directed to a non-elected invention (see 37 CFR 1.142(b) and MPEP 821.03).
To preserve a right to petition, the reply to this action must distinctly and specifically point out supposed errors in the restriction requirement. Otherwise, the election shall be treated as a final election without traverse. Traversal must be timely. Failure to timely traverse the requirement will result in the loss of right to petition under 37 CFR 1.144. If claims are subsequently added, Applicant must indicate which of the subsequently added claims are readable upon the elected invention.
Should Applicant traverse on the ground that the inventions are not patentably distinct, Applicant should submit evidence or identify such evidence now of record showing the inventions to be obvious variants or clearly admit on the record that this is the case. In either instance, if the Examiner finds one of the inventions unpatentable over the prior art, the evidence or admission may be used in a rejection under 35 U.S.C. 103 or pre-AIA 35 U.S.C. 103(a) of the other invention.
Accordingly, only the composition claims 8-15 are under examination as elected by original presentation.
Withdrawal of Rejections
The response and amendments filed on 04/28/2026 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 Rejections
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 8-15 are rejected under 35 U.S.C. 101 because they are drawn to ineligible subject matter (based on the 2019 Revised Patent Subject Matter Eligibility Guidance).
Claim interpretation: regarding claims 8-15’s preambles (e.g., for preventing or treating a bone disease, etc.), the MPEP states that if “the preamble merely states, for example, 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(II): Effect of the Preamble). Thus, the claims are drawn to compositions and not methods of treatments, thereby the preambles have been considered but do not carry patentable weight. Regarding the term “excipient”, under the broadest reasonable interpretation, naturally occurring water reads on said term.
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 read on a naturally occurring stem cell. Although claim 1 recites the functional language/limitation of “having enhanced osteogenic differentiation capacity”, this characteristic is a natural property of stem cells found in nature. For instance,
Bohm (previously cited) discloses during embryonic osteo-lineage specification, MSCs develop or differentiate into committed cells where the key osteogenic transcription factors, Runx2 and Osterix (Osx), drive OPCs to progress to mature OBs;
the instant specification discloses “MSCs of animals including mammal, e.g., humans” (see pre-grant specification at ¶ [0016]); or
MSCs derived from the skull tissue or calvaria of the fetus after an ectopic pregnancy death (see pre-grant specification at ¶ [0018]-[0019]).
In other words, the claimed composition appears to be from natural sources and 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 selecting a subset of cells based on gene or cell surface marker expression, and claiming the 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 04/28/2026 have been fully considered but they are not persuasive and deemed insufficient to overcome the subject matter eligibility requirements.
In response to Applicant’s argument (addressing page 7 of the remarks) that “For the composition claims, a natural counterpart should be compared to the claimed composition. Here, the claimed composition does not exist in nature and has new utility/properties compared to what exists in nature”: this argument is not persuasive because, as noted in the prior office action, it appears that Applicant is selecting a subset of cells based on gene or cell surface marker expression, and claiming the naturally occurring product. The MPEP 2106.04(II)(A) states “When the nature-based product is derived from a naturally occurring thing, then the naturally occurring thing is the counterpart”. The instant specification discloses “MSCs of animals including mammal, e.g., humans” (see pre-grant specification at ¶ [0016]); or MSCs derived from the skull tissue or calvaria of the fetus after an ectopic pregnancy death (see pre-grant specification at ¶ [0018]-[0019]). In other words, the claimed stem cells already exist in nature and Applicant has not shown how the claimed stem cells are markedly different. Thus, Applicant may not merely choose and isolate natural stem cells to claim them as an invention. The MPEP 2106.04(II)(C) states “If there is a change in at least one characteristic as compared to the counterpart, and the change came about or was produced by the inventor’s efforts or influences, then the change will generally be considered a markedly different characteristic such that the claimed product is not a product of nature exception”.
Maintained Rejections
Claim Rejections - 35 USC §103, Obviousness
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 8-15 are rejected under 35 U.S.C. 103 as being unpatentable over Zhang (Side population (SP) cells isolated from fetal rat calvaria are enriched for bone, cartilage, adipose tissue and neural progenitors, 2006) in view of Spring (US 2007/0105101 A1).
Zhang discloses that “skeletal stem and progenitor cells are present in bone marrow stroma as well as other bone compartments such as periosteal and fetal rat calvaria (RC) tissue.
RC cells isolated by sequential enzymatic digestion have provided a useful in vitro model for studying osteoblast differentiation and activity” (see page 662: Introduction). Zhang further teaches that side population (SP) “with increased capacity to undergo differentiation along multiple mesenchymal lineages exists in fetal RC cell populations” (see bridging ¶ of pages 666-667). SP cells isolated from fetal RC are highly enriched for colony-forming progenitors (see page 664: Results) with osteogenesis characteristics (see page 663, left col.: Osteogenesis).
However, Zhang does not teach: expressing at least one gene selected from the group consisting of Osx (base claims’ limitation).
Spring’s disclosure is directed to identifying genes that may be used as markers for the differentiation process (see ¶ [0001]) and further discusses “a need for the investigation of the changes in global gene expression levels, as well as the need for the identification of new molecular markers associated with the differentiation of precursor cells into osteoblasts” (see ¶ [0002]).
Spring discloses “During the process of synthesizing new bone tissue, osteoblasts differentiate from precursor pre-osteoblastic cells to mature bone-forming cells … Many external regulating factors are known, such as TGFβ family members, but critical molecular steps in osteoblast differentiation and bone formation are largely unknown. One key player was identified recently as the transcription factor Cbfa1. Another transcription factor, Osterix (Osx), which cooperates with and is genetically downstream of Cbfa1, has also been identified. The expression levels of various enzymes and structural proteins, for example, alkaline phosphatase and type-I collagen, are up-regulated, while other genes are down-regulated” (see ¶ [0002]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to select the MSC of Zhang based upon the gene expression of Osterix (Osx) such as taught by Spring. The ordinary artisan would have been motivated to do so is because Spring teaches that the transcription factor of Osterix (Osx) was a key player identified in osteoblast differentiation and bone formation. Thus, it would be reasonable for an ordinary artisan to envisage a MSC having enhanced osteogenic differentiation capacity with Osx gene expression following the guidance of the cited references.
Regarding the gene or surface marker expressions, the reference of Zhang is silent regarding the claimed gene or surface marker expressions but there is reason to believe that Zhang’s stem cell will also inherently possess said expressions. The technical reasoning is because both Zhang and the instant stem cells are derived from the calvaria tissue of the fetus. In other words, both Zhang and the instant invention obtained a selected side population (i.e., a subset of cells) stem cells with enhanced osteogenic differentiation capacity from the same tissue site. Zhang teaches “fetal rat calvaria (RC) cells were obtained by sequential enzymatic digestion” (see page 663: Materials and methods) and “RC cells were isolated from the parietal bone of the calvaria, a bone that arises from neural crest” (see page 666, right col.). Nonetheless, Spring teaches that the transcription factor of Osterix (Osx) was a key player identified in osteoblast differentiation and bone formation; and also note that Spring teaches very high expression of sFRP2 was detected (see Spring at ¶ [0080] and page 29: Table 4). In this case, burden is shifted to the Applicant to distinguish the instant invention over the prior art.
Regarding claims 8-15’s preambles (e.g., for preventing or treating a bone disease, etc.), as noted above, the MPEP states that if “the preamble merely states, for example, 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(II): Effect of the Preamble). Thus, the claims are drawn to compositions and not methods of treatments, thereby the preambles have been considered but do not carry patentable weight. Nonetheless, note that Spring discloses “in a number of clinical applications, it may desirable to enhance the rate of bone formation by promoting the differentiation of precursor pre-osteoblastic cells into osteoblasts. One application that is particularly important is the treatment of osteoporosis, characterized by a decrease in bone mass making the bones more fragile and subject to fracture” (see Spring at ¶ [0002]).
Examiner’s Response to Arguments
Applicant’s amendments and arguments filed on 04/28/2026 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 page 8 of the remarks) that the cited references do not teach or suggest the combined use of SFRP2 as a co-marker together with Osx: this argument is not persuasive because, as noted in the prior office action, the reference of Zhang is silent regarding the claimed gene or surface marker expressions but there is reason to believe that Zhang’s stem cell will also inherently possess said expressions. The technical reasoning is because both Zhang and the instant stem cells are derived from the calvaria tissue of the fetus. In other words, both Zhang and the instant invention obtained a selected side population (i.e., a subset of cells) stem cells with enhanced osteogenic differentiation capacity from the same tissue site. Zhang teaches “fetal rat calvaria (RC) cells were obtained by sequential enzymatic digestion” (see page 663: Materials and methods) and “RC cells were isolated from the parietal bone of the calvaria, a bone that arises from neural crest” (see page 666, right col.). Furthermore, the cited reference of Spring teaches that the transcription factor of Osterix (Osx) was a key player identified in osteoblast differentiation and bone formation; and also note that Spring teaches very high expression of sFRP2 was detected (see Spring at ¶ [0080] and page 29: Table 4). Thus, it would be reasonable for an ordinary artisan to envisage a MSC having enhanced osteogenic differentiation capacity with Osx gene expression following the guidance of the cited references.
Conclusion
Claims 8-15 are rejected.
Claims 16-23 are withdrawn from consideration.
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
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NGHI V NGUYEN whose telephone number is (571)270-3055. The examiner can normally be reached Mon-Fri: 9 - 3 pm (EST).
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/NGHI V NGUYEN/Primary Examiner, Art Unit 1653
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