DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
2. Applicant’s election of the species of RPL5 in the reply filed on 28 October 2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claim Status
3. Claims 52-80 are pending.
Claims 55-69 and 71-80 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected species, there being no allowable generic or linking claim.
Claims 52-54 and 70 read on the elected invention and have been examined herein. It is noted that claim 54 encompasses the non-elected species of the genes other than RPL5 and combinations of the recited genes. Prior to the allowance of claims, any non-elected species which have not been rejoined with the elected species will be required to be removed from the claims.
Priority
4. The continuing information provided at page 1 of the specification is not complete and is not consistent with the information provided in the Application Data Sheet (ADS). The specification states “This application is a continuation-in-part of PCT International Application No. PCT/US2018/64322, filed December 6, 2018, and claims the benefit of U.S. Provisional Application No. 62/596,588, filed December 8, 2017, and PCT
International Application No. PCT/US2018/64322, filed December 6, 2018,” However, the present application was not co-pending with the PCT application or provisional application since the present application was filed more than a year after the filing of the PCT and provisional applications. The specification should be amended to clarify the relationship between the present application and the priority applications, as consistent with the ADS. In particular, the first line of the specification should be amended to recite, for example: “This application is a continuation of U.S. Application 16/434,362, filed June 7, 2019, which is a continuation-in-part of International Application PCT/US2018/64322, filed December 6, 2018, which claims the benefit of U.S. Provisional Application No. 62/596,588, filed December 8, 2017.”
5. Claims 52-53 are entitled to priority to provisional application 62/596,588, filed 08 December 2017. Claims 54 and 70 are entitled to priority to U.S. Application 16/434,362 filed 07 June 2019. It is noted that a claim as a whole is assigned an effective filing date rather than the subject matter within a claim being assigned individual effective filing dates. Neither International Application PCT/US2018/64322 or U.S. Provisional Application No. 62/596,588 provide support for each of the genes listed in claims 54 and 70, and particularly do not disclose that the cell population expresses the elected gene of RPL5, particularly at an expression level of greater than 794.88 RNA transcripts per million RNA transcripts.
See MPEP 2163 II at “(b) New Claims, Amended Claims, or Claims Asserting Entitlement to the Benefit of an Earlier Priority Date or Filing Date under 35 U.S.C. 119, 120, 365, or 386” states “To comply with the written description requirement of 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph, or to be entitled to an earlier priority date or filing date under 35 U.S.C. 119, 120, 365, or 386, each claim limitation must be expressly, implicitly, or inherently supported in the originally filed disclosure.”
Claim Rejections - 35 USC § 101
6. 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 52-54 and 70 are rejected under 35 U.S.C. 101 because the claimed invention is directed to the judicial exception of a natural phenomenon / naturally occurring product without significantly more. The judicial exception is not integrated into a practical application and the claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception for the reasons that follow.
Applicant’s attention is directed to MPEP 2106 “Patent Subject Matter Eligibility” and particularly 2106.04(b)II and 2106.04(c) “Examples of Products Lacking Markedly Different Characteristics.”
Regarding Step 1 of the analysis, the claims are directed to the statutory category of a product.
Regarding Step 2A, prong one, the claims recite the judicial exception of a natural phenomenon – i.e., a naturally occurring product.
The claims recite a composition of matter comprising a population of synchronized cultured human skin fibroblasts, wherein at least 95% of the cells in the population in the composition are synchronized, and particularly wherein the human skin cell fibroblasts are from a human subject suspected of having dementia (claims 53, 54 and 70), and express the RPL5 gene at a level consistent with that of Alzheimer’s disease patients (claims 54 and 70), and specifically at a level of 794.88 RNA transcripts per million RNA transcripts.
The population of synchronized cultured human skin fibroblasts constitute a naturally occurring product. The population of synchronized cultured human skin fibroblasts do not have any markedly different characteristics from their naturally occurring counterparts of human skin fibroblasts. Note that there is nothing in the specification or any evidence of record to establish that the broadly claimed human skin fibroblasts are markedly different as compared to their naturally occurring counterparts. On the contrary, the specification discloses that the population of cultured human skin fibroblasts have the same properties and expression pattern as their naturally occurring counterparts from human patients having Alzheimer’s disease.
Regarding Step 2A, prong two, having determined that the claims recite a judicial exception, it is then determined whether the claims recite additional elements that integrate the judicial exception into a practical application.
Herein, the claims do not recite additional elements that integrate the recited judicial exception into a practical application of the exception..
Regarding Step 2B, the next question is whether the remaining elements – i.e., the non-patent-ineligible elements - either in isolation or combination, amount to significantly more than the judicial exception.
Herein, the claims do not recite any non-patent-ineligible elements in addition to the nature based products.
For the reasons set forth above, the claims are not considered to recite something significantly different than a judicial exception and thereby are not directed to patent eligible subject matter.
Improper Markush Grouping Rejection
7. Claims 54 and 70 are rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush groupings of the AC004057.1,AC092651.1, ACP6, ADAM20, ASXL2, C2CD5, CARNS1, FAMl49B1,GLIS3-AS1, IL18R1, LINC01393, LZIC, MAP1LC3B2, NHLH1, NORAD, NPPA-AS1_3, OSMR-AS1, PAN3, PHBP8, PSMB9, RAB3IP, RDH16,RFESDP1, RPL5, SCG2, SDHD, SHISA5, SLC45A3, SNHG14, TTC26, URB2, USMG5, WASF2, ZCWPW2, ZNF444, and ZNF70 genes and combinations thereof are improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons:
It is first noted that MPEP 2117 states that “A Markush claim may be rejected under judicially approved "improper Markush grouping" principles when the claim contains an improper grouping of alternatively useable members. A Markush claim contains an "improper Markush grouping" if either: (1) the members of the Markush group do not share a "single structural similarity" or (2) the members do not share a common use. Supplementary Guidelines at 7166 (citing In re Harnisch, 631 F.2d 716, 721-22, 206 USPQ 300, 305 (CCPA 1980)). Members of a Markush group share a “single structural similarity” when they belong to the same recognized physical or chemical class or to the same art-recognized class (prong 1) and the members of a Markush group share a common function or use when they are disclosed in the specification or known in the art to be functionally equivalent (prong 2).
The phrase “significant structural element is shared by all of the alternatives” refers to cases where the compounds share a common chemical structure which occupies a large portion of their structures, or in case the compounds have in common only a small portion of their structures, the commonly shared structure constitutes a structurally distinctive portion in view of existing prior art, and the common structure is essential to the common property or activity.
A recognized physical class, a recognized chemical class, or an art-recognized class is a class wherein “A recognized physical class, a recognized chemical class, or an art-recognized class is a class wherein there is an expectation from the knowledge in the art that members of the class will behave in the same way in the context of the claimed invention. In other words, each member could be substituted one for the other, with the expectation that the same intended result would be achieved.” (see MPEP 2117IIA).
Herein, the recited alternative species do not share a single structural similarity, as each gene has a different chemical structure in that it consists of a different nucleotide sequence. The only structural similarity present is that all of the genes comprise nucleotides. The fact that the genes comprise nucleotides per se does not support a conclusion that they have a common single structural similarity because the structure of comprising nucleotides alone is not essential to the asserted common activity of being correlated with Alzheimer’s disease. Accordingly, while the different genes are asserted to have the property of having an expression level in synchronized human skin cell fibroblasts that is consistent with / indicative of Alzheimer’s disease, they do not share a substantial structural similarity essential to this activity.
Further, the recited genes do not belong to a chemical or art-recognized class because there is no expectation from the knowledge in the prior art that the genes behave in the same manner and can be substituted for one another with the same intended result achieved. There is no evidence of record to establish that it is clear from their very nature that the recited genes possess the common property of having an expression level in synchronized human skin cell fibroblasts that is consistent with / indicative of Alzheimer’s disease.
Following this analysis, the claims are rejected as containing an improper Markush grouping.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
Claim Rejections - 35 USC § 102
8. In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
Claim(s) 52-54 and 70 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Alkon et al (U.S. 20100021913), as evidenced by the present specification at p. 17, lines 1-10.
Alkon teaches a population of cultured human skin fibroblast cells that were grown to 90-100% confluence stage and then starved.in serum-free medium (para [0065]). It is considered to be a property of this population of cultured human skin fibroblast cells that at least 95% of the cells in the population are synchronized (i.e., in the same cell cycle stage). This finding is evidenced by the teachings in the specification at p. 17, lines 1-10, and particularly the statement “Cell confluence followed by serum starvation typically arrests the cells in the G0/G1 stage.” Note that the specification is cited only to establish what is inherent to the teachings of Alkon.
Regarding claims 53, 54 and 70, Alkon teaches that the cultured skin cell fibroblasts are from a human subject having dementia and particularly Alzheimer’s disease (“AD”; e.g., para [0065]).
Regarding claims 54 and 70, in the absence of evidence to the contrary, it is considered to be a property of the population of synchronized cultured skin cell fibroblasts from a human subject having Alzheimer’s disease and thereby dementia that the level of expression of the RPL5 gene in the population of cells is “consistent” with that in synchronized cells derived from Alzheimer’s disease patients, and particularly the expression level is greater than 794.88 RNA transcripts per million RNA transcripts. The present claims do not recite any specific structural properties of the population of synchronized cultured human skin fibroblast cells that distinguish this population of cells over the population of cells disclosed by Alkon. The present claims also do not define the synchronized cells in terms of any specific process by which they are made which would distinguish the claimed population of cells over that of Alkon. Since the population of cultured human skin fibroblast cells of Alkon are obtained from human subjects having Alzheimer’s disease and are synchronized by culturing the cells to confluence and then starving the cells in serum-free medium, the population of cells is also expected to express the RPL5 gene at a level consistent with the level that in corresponding synchronized cells derived from Alzheimer's disease patients - i.e., at a level of greater than 794.88 RNA transcripts per million RNA transcripts.
The burden is shifted to Applicant to establish that the claimed compositions comprising a population of synchronized cultured skin cell fibroblasts are distinct form the compositions comprising a population of cultured skin cell fibroblasts of Alkon that are cultured by growing to confluence and then starved in serum-free medium and thereby synchronized. See MPEP 2112 V:
“[T]he PTO can require an applicant to prove that the prior art products do not necessarily or inherently possess the characteristics of his [or her] claimed product. Whether the rejection is based on ‘inherency’ under 35 U.S.C. 102, on ‘prima facie obviousness’ under 35 U.S.C. 103, jointly or alternatively, the burden of proof is the same.” In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433-34 (CCPA 1977) (footnote and citation omitted). The burden of proof is similar to that required with respect to product-by-process claims. In re Fitzgerald, 619 F.2d 67, 70, 205 USPQ 594, 596 (CCPA 1980) (citing Best, 562 F.2d at 1255).
It is also noted that in view of the open claim language of “comprising,” the composition of matter may comprise additional cells and only a subpopulation of the cells in the composition needs to meet the limitation that 95% of the cells are synchronized or have the expression levels of RPL5 set forth in claims 54 and 70.
9. Claim(s) 52 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Cao, K. (U.S. 20170246177), as evidenced by the present specification at p. 17, lines 1-10.
Cao (para [0153]) teaches “Skin fibroblasts were grown on 35-mm glass bottom dish until 60% confluence. For G1 phase synchronization, fibroblast cells were synchronized by serum starvation for 24 hours.” Cao (para [0150]) teaches that the skin fibroblasts are human skin fibroblasts. It is considered to be a property of this population of cultured human skin fibroblast cells that at least 95% of the cells in the population are synchronized (i.e., in the same cell cycle stage). This finding is evidenced by the teachings in the specification at p. 17, lines 1-10, and particularly the statement “Cell confluence followed by serum starvation typically arrests the cells in the G0/G1 stage.” Note that the specification is cited only to establish what is inherent to the teachings of Cao.
The burden is shifted to Applicant to establish that the claimed compositions comprising a population of synchronized cultured skin cell fibroblasts are distinct form the compositions comprising a population of cultured skin cell fibroblasts of Cao that are cultured by growing to confluence and then starved in serum-free medium to synchronize the cells at stage G1. See MPEP 2112 V:
“[T]he PTO can require an applicant to prove that the prior art products do not necessarily or inherently possess the characteristics of his [or her] claimed product. Whether the rejection is based on ‘inherency’ under 35 U.S.C. 102, on ‘prima facie obviousness’ under 35 U.S.C. 103, jointly or alternatively, the burden of proof is the same.” In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433-34 (CCPA 1977) (footnote and citation omitted). The burden of proof is similar to that required with respect to product-by-process claims. In re Fitzgerald, 619 F.2d 67, 70, 205 USPQ 594, 596 (CCPA 1980) (citing Best, 562 F.2d at 1255).
It is also noted that in view of the open claim language of “comprising,” the composition of matter may comprise additional cells and only a subpopulation of the cells in the composition needs to meet the limitation that 95% of the cells are synchronized
9. The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Lueking et al (U.S. 20130029864) teaches the correlation between protein expression of RPL5 in cerebrospinal fluid samples (RPL5) of human subjects and Alzheimer’s disease (para [0053], Table A and claim 8).
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CARLA J MYERS whose telephone number is (571)272-0747. The examiner can normally be reached M-Th 6:30-5:00 EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Wu-Cheng Winston Shen can be reached on 571-272-3157. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/CARLA J MYERS/Primary Examiner, Art Unit 1682