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 1-15 are pending (claim set as filed on 10/23/2023).
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.
Information Disclosure Statement
The Information Disclosure Statements (IDS) submitted on 10/23/2023, 02/28/2025, and 05/29/2025 are acknowledged. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the IDSs are being considered by the Examiner.
Drawings
The drawings filed on 10/23/2023 have been accepted.
Claim Rejections - 35 USC §101, Subject Matter Eligibility
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-15 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.
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 (reference cited below) 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;
dependent claims 6-7 require “wherein the stem cell is derived from tissue of an ectopic or stillborn fetus” (i.e., the stem cells are obtain from a natural source);
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.
Claim Rejections - 35 USC §102, Anticipation
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.
Claims 1 and 8-13 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Bohm (Activation of Skeletal Stem and Progenitor Cells for Bone Regeneration Is Driven by PDGFRβ Signaling, 2019 - cited by the ISA and in the IDS filed on 10/23/2023).
Bohm discloses “During embryonic osteo-lineage specification, mesenchymal skeletal stem cells (SSCs) or populations of skeletal stem and progenitor cells (SSPCs) differentiate into committed osteoprogenitor cells (OPCs). The key osteogenic transcription factors, Runx2 and Osterix (Osx), drive OPCs to progress to mature OBs expressing type I collagen (Col1) and later osteocalcin” (see page 236, left col. Introduction). The fetal osterix (Osx)-expressing cells represent capability to repair skeletal or bone injury (see page 236: Summary).
Claim Rejections - 35 USC §103, Obviousness
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 1-15 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).
Regarding claims 6-7, 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.).
However, Zhang does not teach: expressing at least one gene selected from the group consisting of Osx (claim 1’s 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 claims 2-5 pertaining to 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. 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]).
Conclusion
No claims were allowed.
Correspondence Information
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/NGHI V NGUYEN/Primary Examiner, Art Unit 1653