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 1-16, 18-27, 29, 31, 33, 40, and 42-45 are pending (claim set as filed on 06/22/2026).
Election/Restrictions
Applicant’s election without traverse of Group II, composition claims, in the reply filed on 06/22/2026 is acknowledged. Method claims 1-15 and 42-45 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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, only composition claims 16, 18-27, 29, 31, 33, and 40 are under examination.
Priority
This application is a 371 of PCT/US2022/022989, which provisional applications to:
(a) PRO 63/170,033 filed on 04/02/2021; and (b) PRO 63/170,137 filed on 04/02/2021.
Drawings
The drawings filed on 10/02/2023 have been accepted.
Information Disclosure Statement
The Information Disclosure Statement (IDS) submitted on 10/02/2023 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.
Abstract Objection
The abstract of the disclosure is objected to because it does not comply with the proper language and format (see MPEP 608.01(b)). Appropriate correction is required.
Applicant is reminded of the proper language and format for an abstract of the disclosure. The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words. It is important that the abstract not exceed 150 words in length since the space provided for the abstract on the computer tape used by the printer is limited. The form and legal phraseology often used in patent claims, such as “means” and “said” should be avoided. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details. The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns”, “The disclosure defined by this invention”, or “The disclosure describes”, etc.
Claim Objections
Claim 22 is objected to for a minor informality because it lacks a period to conclude the sentence.
Claim Rejections - 35 USC §112, Indefinite
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.
Claims 16 and 18-26 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Claim 16’s last limitation recites the phrase “and the composition comprises one or more factors to maintain the IMPACS in an undifferentiated state” and therefore, renders the claim indefinite because the metes and bounds is unclear. The drafting language of said phrase employs a functional limitation “when it recites a feature ‘by what it does rather than by what it is’”. MPEP 2173.05(g) states that “the use of functional language in a claim may fail ‘to provide a clear-cut indication of the scope of the subject matter embraced by the claim’ and thus be indefinite ... the boundaries of the claim scope may be unclear”. For instance, the claimed term “factor” is vague but might imply, at best, a growth factor (e.g., a protein polypeptide or steroid hormone) to achieve its effect, but it is not definitively clear. Moreover, the specification does not appear to provide a definition for said phrase, nor does there appear to be any examples of factors that can achieve the intended function. In other words, one of ordinary skill in the art cannot immediately envisage what this/these factor(s) is/are or how many are required to maintain the cells in an undifferentiated state. Appropriate clarification is requested.
Examiner’s note: MPEP 2173.05(g) further states “During prosecution, Applicant may resolve the ambiguities of a functional limitation in a number of ways. For example: … Applicant could demonstrate that the specification provides a general guideline and examples sufficient to teach a person skilled in the art when the claim limitation was satisfied; or (4) Applicant could amend the claims to recite the particular structure that accomplishes the function”. Applicant is advised that a rejection based upon §112(a) for lacking written description may be appropriate dependent upon Applicant’s support from the specification.
Claims 18-26 are rejected because they are dependent claims that do not overcome the deficiencies of the rejected claim from which they depend.
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 16, 18-27, 29, 31, 33, and 40 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).
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., cells that exist in nature). 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 cell or at least one that substantially resembles one. The instant specification discloses:
the human Immune Modulatory Paracrine Acting Cells (IMPACs) are isolated from human bone or fragments thereof (see pre-grant spec at ¶ [0009], [0127], [0156]).
the IMPACs are obtained from sources comprising: autologous, allogeneic, et. al. (see ¶ [0017], [0129]).
human bone-derived IMPACs have stem cell like phenotypes and growth kinetics (see ¶ [0157]).
these results show that the IMPACs resemble primitive cells that resides deeper into the bone expressing hESC markers (see ¶ [0158]).
IMPACs abundantly expressed a common stem cell antigen CD49f and embryonic surface antigens signifying their primitive nature (see ¶ [0186]).
Human MSC lack surface expression of CD45, CD34, CD11b (see ¶ [0159]-[0162]).
Cardiomyocyte are muscle cells of the heart (see ¶ [0033]).
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 §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 16, 18-27, 29, 31, 33, and 40 are rejected under 35 U.S.C. 103 as being unpatentable over Pittenger (US 2012/0141438 A1) in view of Sid-Otmane (Mesenchymal Stem Cell Mediates Cardiac Repair through Autocrine, Paracrine and Endocrine Axes, 2020) – references cited by the ISA and in the IDS filed on 06/22/2026.
Pittenger’s general disclosure relates to compositions and methods for repairing and/or regenerating cardiac tissue by administering adult bone marrow-derived mesenchymal stem cells to an individual (see abstract). Pittenger discloses that “adult bone marrow is an accessible and renewable source of adult stem cells that can be greatly expanded in culture”, which are used to regenerate or repair striated cardiac muscle that has been damaged through disease or degeneration (see ¶ [0006]-[0007], [0012]).
However, Pittenger does not expressly teach: paracrine acting cells.
Sid-Otmane teaches “mesenchymal stem cells (MSC) represent a strong candidate to heal the infarcted myocardium. While differentiation potential has been described as a possible avenue for MSC-based repair, their secreted mediators are responsible for the majority of the ascribed pro-healing effects. MSC can either promote their own survival and proliferation through autocrine effect or secrete trophic factors that will act on adjacent cells through a paracrine effect” (see abstract & page 4, left col. 2nd ¶).
Sid-Otmane teaches “Exosomes as well as other trophic factors are the main actors of the immunoregulatory effect provided by MSCs. The main elucidated mechanisms in immunoregulation involve indoleamine 2,3-deoxygenase (IDO) or inducible nitric oxide synthase (iNOS), depending on the source of MSCs. IDO is an enzyme that catabolizes tryptophan and iNOS produces NO and both mediators can inhibit T cells. Genetic knockdowns of these enzymes proved their implication in the immuno-suppression, but the exact mechanisms are still unclear. Some direct interaction between MSCs and immune cells can also occur. Expressed factors on MSCs such as the co-stimulatory factors PDL1 and FASL can inhibit activated T cells by binding to CD80” (see page 5, right col. 4th ¶). Sid-Otmane teaches “Extracellular vesicles (EVs) are now recognized as important intercellular messengers involved in transmission of biological signals including proteins, lipids and RNAs. Exosomes are one subgroup of EVs originating from the fusion of multivesicular bodies and plasma membrane of stem cells and are retrieved in the secretome of MSCs of different origins. They are particularly enriched with mRNAs or micro RNAs (miRNAs) … MSC derived exosomes are accountable for the cardioprotective effects as their depletion from the conditioned media suppressed this protection” (see page 4, right col. 2nd ¶).
Since Pittenger teaches use of bone marrow derived MSC to treat cardiac disease or damage, and Sid-Otmane teaches that MSC act by paracrine mechanisms, it would have been obvious to an artisan of ordinary skill in the art to prepare cells equivalent to the claimed IMPACS such as for use for administering to a subject having cardiac disease or damage.
Regarding the IMPACs expression markers, Pittenger teaches “Cell preparations having greater than about 95%, usually greater than about 98%, of adult human bone marrow derived stem cells can be achieved using techniques for isolation, purification, and culture expansion of stem cells. For example, isolated, cultured mesenchymal stem cells can comprise a single phenotypic population (about 95% or about 98% homogeneous) by flow cytometric analysis of expressed surface antigens. The desired cells in such composition can be identified, for example, by expression of a cell surface marker (e.g., CD73 or CD105) specifically bound by an antibody produced from hybridoma cell line SH2, ATCC accession number HB 10743, an antibody produced from hybridoma cell line SH3, ATCC accession number HB 10744, or an antibody produced from hybridoma cell line SH4, ATCC accession number HB 10745. Such antibodies selectively bind bone marrow-derived mesenchymal stem cells and, therefore, can be used to identify, quantify, isolate, or purify mesenchymal stem cells from bone marrow samples” (see ¶ [0016]). Pittenger further teaches “the adult bone marrow-derived stem cells are induced or genetically modified or engineered to express proteins of importance for the differentiation and/or maintenance of striated muscle cells. Some examples include growth factors (TGF-β, IGF-1, FGF), myogenic factors (myoD, myogenin, Myf5, MRF), transcription factors (GATA-4), cytokines (cardiotrophin-1), members of the neuregulin family (neuregulin 1, 2 and 3) and homeobox genes (Csx, tinman, NKx family). Also contemplated are genes that encode for factors that stimulate angiogenesis and revascularization (e.g., vascular endothelial growth factor (VEGF)). Any of the known methods for introducing DNA are suitable, however electroporation, retroviral vectors and adeno-associated virus (AAV) vectors are preferred” (see ¶ [0020]). Although the claimed markers are not expressly taught by the prior art, it would have been readily apparent and within the purview of the ordinary artisan to either select the desired phenotype via isolation or via genetic modification.
Conclusion
No claims were allowed.
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 (ET).
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/NGHI V NGUYEN/Primary Examiner, Art Unit 1653
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