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 1-8, 10-13, and 15 are pending in the application.
Claims 10-13 and 15 are withdrawn.
Claims 1-8 are the subject of this office action.
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-8 in the reply filed on 12 November 2025 is acknowledged.
Claims 10-13 and 15 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 12 November 2025.
Priority
The instant application is a 371 National Stage of PCT/US2021/047283, filed 24 August 2021, which claims benefit of provisional application 63/069,477, filed 24 August 2020.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 24 July 2023 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the examiner.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01. See at least the following instances in the specification:
Pg. 1, Ln. 18
Pg. 26, entry 1
The list of therapies recited on at least Pg. 11, Ln. 22-Pg. 12, Ln. 2, and Pg. 13. Ln. 31-32-Pg. 14, Ln. 9 contains a number of terms which are trade names or marks used in commerce.
The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-2 and 4-8 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for the diagnosing and treating osteoporosis using quantification of a specific phenotype of OECs, does not reasonably provide enablement for the diagnosis and treatment of any skeletal disease by quantification of any phenotype of OECs. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims.
A determination of enablement involves the consideration of the following factors: the breadth of the claims; the nature of the invention; the state of the prior art; level of one or ordinary skill; level of predictability in the art; amount of direction provided by the inventor; existence of working examples; and quantity of experimentation needed to make or use the invention based on the content of the disclosure.
Regarding the breadth of the claims and the nature of the invention: the claims are directed to a method of diagnosing and treating a skeletal disease. The claims encompass diagnosis and treatment of any skeletal disease, wherein the instant specification provides the following definition of a skeletal disease (Pg. 7, Ln. 6-8: skeletal disease refers to any condition associated with the bone or joints, including those associated with bone loss, bone fragility, or softening, or aberrant skeletal growth). As such, the claims encompass diagnosis and treatment of a very broad genus of diseases which are characterized by a very broad range of causes, symptoms, and mechanisms (i.e. diseases characterized by bone loss such as osteoporosis and osteopenia; autoimmune conditions such as rheumatoid arthritis and lupus; various species of cancers and tumors; diseases characterized by an increase in bone density, such as osteopetrosis).
The diagnosis of skeletal disease recited in the claim is based on identification and quantification of “osteoclast-enhancing cells” (OECs) which, according to the instant specification (Pg. 8, Ln. 7-17), encompasses any cell which enhances human osteoclastogenesis and which can be characterized and identified by a number of different phenotypes and surface markers (see specification Pg. 8, Ln. 7-17; Pg. 22, Ln. 18-22; Pg. 23, Ln. 11-25; Table 1; claims 6-7). Further, the claims encompass identification and quantification of OECs in any sample type taken from a subject.
Regarding the state of the prior art, level of predictability in the art, and the level of ordinary skill in the art: Atkins et al (RANK Expression as a cell surface marker of human osteoclast precursors in peripheral blood, bone marrow, and giant cell tumors of bone. Journal of Bone and Mineral Research. September 2006. Vol. 21, No. 9, pages 1339-49.; IDS entered) teaches a possible correlation between OECs (CD14+RANKhigh cells) and the diagnosis and management of diseases characterized by abnormal osteoclastic activity and increased bone resorption such as osteoporosis (Abstract; Pg. 1340, Col. 1, Par. 3). Atkins demonstrates quantification of OECs in a patient sample and theorizes that such quantification may be useful in the identification and management of diseases such as osteoporosis, but Atkins does not compare quantitative levels of OECs in samples from patients with osteoporosis with levels of OECs in samples from control patients in order to actually diagnose osteoporosis based on an increase in OEC levels. Data provided by Atkins only identifies and quantifies OECs in healthy control patients (Pg. 1340, Col. 1, Par. 1)
The teachings of Atkins do not support diagnosis of any skeletal disease based on quantification of an increase in OECs in a patient as compared to a control subject. In fact, the teachings of Atkins show that OEC activity and OC activity would be expected to vary in different skeletal diseases, and thus indicate that there is not a predictable relationship between increased OEC and any and all skeletal diseases. For example, while one might expect that diseases such as osteoporosis which are characterized by a decrease in bone density and an increase in bone resorption may be detected by an increase in OECs or an increase in osteoclast expression or osteoclastic activity, this is likely not the case for skeletal diseases which may cause a decrease in bone resorption and an increase in bone density, such as osteopetrosis (Pg. 1347, Col. 1, Par. 2: Genetically modified mice deficient for RANK or its sole ligan RANKL, have an almost complete lack of OCs, and as a consequence, are severely osteopetrotic).
Ritchlin et al (US 2006/0275834 A1; IDS entered) teaches a method comprising identification and quantification of OECs in the diagnosis and treatment of inflammatory joint conditions such as rheumatoid arthritis and psoriatic arthritis, which are considered skeletal diseases according to the instant disclosure. Ritchlin teaches that increases in OEC expression in a patient sample as compared to a healthy control may indicate the presence of an inflammatory joint condition (Par. 3: diagnosing and treating inflammatory joint disease; Par. 95: obtaining a sample from the subject and assaying the number of OCPs in the sample, wherein an increase in OCP compared to a healthy control indicates an inflammatory joint disease in the subject; Par. 51: condition diagnosed may be RA or PsA).
Ritchlin further teaches that osteoclast expression may differ across sample types wherein this teaching, absent more specific evidence to the contrary, would seem to indicate that there is not a predictable or conserved trend in osteoclast or OEC expression across all different sample types (Fig. 8A shows significant differences in osteoclast expression in different sample types and shows different trends in OC expression between different groups based on sample type (i.e. there is a significant different in OC expression between groups in blood and spleen samples, but there is no significant difference in OC expression between groups in bone marrow samples)).
As such, the level of predictability in the art for one of ordinary skill in the art is low, as the prior art does not demonstrate a conserved or predictable trend in OEC expression across all different types of skeletal diseases and all different types of biological samples.
For most skeletal diseases encompassed by the instant claims, there is no specific data in the prior art which compares OEC levels in patients with the disease and control patients to show that patients with any skeletal disease can be identified by in increase in OEC levels.
Regarding amount of direction provided by the inventor and the existence of working examples:
The disclosure provides a number of possible variations on the phenotype of OECs which are identified and quantitated in the method of diagnosis and treatment (see specification Pg. 8, Ln. 7-17; Pg. 22, Ln. 18-22; Pg. 23, Ln. 11-25; Table 1; claims 6-7). The disclosure provides reduction to practice for the identification and quantification of OECs in PBMCs isolated from patient blood samples (Pg. 17, Ln. 19-Pg. 18, Ln. 2) wherein RANKhigh/CD66b negative cells on CD14+ cells are named as OECs. The specification indicates that there is increased cell surface expression of CCR2, C3AR1, CD51/CD61, and HLA-DR on this population of OECs in samples from 3 healthy subjects (Pg. 22, Ln. 13-17), but does not provide support which shows that these trends are also true in the OECs of patients with skeletal diseases.
Regarding reduction to practice for a method of diagnosis and treatment, the disclosure provides only one working example/reduction to practice for the diagnosis of osteoporosis based on quantification of OECs by RANK, CD14, CD235a, and CD66b. The example shows that the percentage of OECs was increased in osteoporosis patients as compared to normal BMD subjects and osteopenia, but that there was no difference in percentage of OECs between normal BMD subjects and subjects with osteopenia. Further, the absolute number of OECs among the three groups indicates that the number of OECs is significantly higher in osteoporosis patients as compared to normal BMD subjects and subjects with osteopenia, but there was no difference between normal BMD subjects and osteopenia (Pg. 23, Ln. 11-25).
As such, the data provided in the disclosure supports diagnosis of osteoporosis based on OEC quantification (by CD14, RANK, CD235a, and CD66b) in PBMCs isolated from a patient blood sample. However, the disclosure does not support or reduce to practice diagnosis of any other kind of skeletal disease based on quantification of OECs from any other sample type. To the contrary, the example provided in the specification explicitly states that there is no significant difference in absolute number or percentage of OECs between patients with osteopenia and control subjects, such that the disclosure specifically teaches against diagnosis of osteopenia based on the claimed method steps.
The disclosure does not provide additional data or support which would indicate that the demonstrated correlation between OEC quantification and osteoporosis diagnosis would be conserved across all different sample types and all different species of skeletal disease which are encompassed by the claim. The specific teachings of the disclosure regarding osteopenia further indicate that the method as claimed is not fully enabled even for the subset of skeletal diseases which are characterized by decreased bone density and increased bone resorption. The specification also does not provide reduction to practice for diagnosis based on different phenotypes of OECs other than the one specifically discussed in the example of Pg. 23, Ln. 11-25.
Regarding the quantity of experimentation needed to make or use the invention based on the content of the disclosure: the quantity of experimentation needed to make or use the invention based on the content of the disclosure is undue. Enablement requires that the disclosure provide a reasonable level of detail which would enable one of ordinary skill in the art to understand and carry out the invention. In the instant case, such reasonable detail is lacking. There are numerous embodiments within the scope of the instant claims which are not reasonably supported or enabled by the instant disclosure or by the prior art.
For all these reasons, and when taken together with the breadth of the claims, the specification fails to teach one of ordinary skill in the art how to make and use the claimed invention in its full scope without undue experimentation.
Claim Rejections - 35 USC § 112(b)
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.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-8 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 1-5 and 8 are rejected as indefinite because the metes and bounds of the term “osteoclast-enhancing cells (OECs)” are unclear. The specification indicates that this term is a new classification (Specification, Pg. 8, Ln. 7-10: a new circulating cell population from human blood, termed OECs. OECs enhance human osteoclastogenesis and express essential osteoclast-specific receptors such as CSF1R and RANK, but do not express CD66b, CD3, and CD19), which does not appear to be commonly recognized or used in the art. The metes and bounds of the term are unclear because it defines a particular population of cells by their function (i.e. osteoclast enhancing) but does not define the structural features that are common to the population or which are responsible for imparting that function. Additionally, the additional structural detail provided in the specification does not resolve this issue because the specification and claims identify these cells by multiple different markers and phenotypes, such that it is not clear which phenotypes, markers, or other structural features of a cell are specifically required to classify a particular cell as an OEC. For example, the specification indicates that OECs do not express CD3 and CD19, but the claims do not indicate that CD3- and/or CD19- is required in the phenotype of OECs quantified in the claimed method. The specification also indicates that OECs “express essential osteoclast-specific receptors such as CSF1R”, but CSF1R+ is not a requirement of the claimed phenotypes of OECs recited in claims 6-7.
Claim 1 is vague regarding “the presence” and “the number”. There is no prior introduction of “a presence” or “a number” in the claim, therefore there is insufficient antecedent basis for this limitation in the claim.
Claims 6-7 are vague regarding “the phenotype”. There is no prior introduction of “a phenotype” in the claims, therefore there is insufficient antecedent basis for this limitation in the claims.
Claim 8 is unclear because it recites treating a subject for osteoporosis when no limitation to a diagnosis of osteoporosis has been provided. Claim 1 from which claim 8 depends recites diagnosis of any skeletal disease, which is a much broader genus that includes osteoporosis. For the purposes of applying prior art in the present office action, claim 8 is understood to require that the subject has been diagnosed with osteoporosis specifically, and not with a different type of skeletal disease. Clarification is required.
Dependent claims 2-5 and 8 are rejected as indefinite because they depend from an indefinite claim and fail to remedy its deficiencies.
Claim Rejections - 35 USC § 101
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 1-6 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (namely a law of nature/natural phenomenon, and abstract idea) without significantly more.
Claims 1-6 are directed to a method of diagnosing and treating a skeletal disease in a subject, by quantification of circulating OECs in a sample from the subject. Wherein diagnosis is based on quantification of OECs constitutes an abstract process that may be performed in the human mind (i.e a practitioner uses OEC data to draw a conclusion about skeletal disease).
The claims are also understood to be directed to a law of nature/natural phenomenon, wherein the correlation between levels of a biomarker/cell population (OECs) and a particular disease state or risk (i.e. the naturally occurring relationship between OEC levels and skeletal disease) is a law of nature/natural phenomenon.
Similar concepts have been held by the courts to constitute law of nature/natural phenomena, as in the identification of a correlation between the presence of myeloperoxidase in a bodily sample (such as blood or plasma) and cardiovascular disease risk in Cleveland Clinic Foundation v. True Health Diagnostics LLC, 859, F.3d 1352, 1361, 123 USPQ2d 1081, 1087 (Fed. Cir. 2017), and the natural relationship between a patient’s CYP2D6 metabolizer genotype and the risk that the patient will suffer QTc prolongation after administration of iloperidone in Vanda Pharmaceuticals Inc v. West-Ward Pharmaceuticals, 887 F.3d 1117, 1135-36, 126 USPQ2d 1266, 1281 (Fed. Cir. 2018). (See MPEP 2106.04(b)).
The correlation is naturally occurring and is a judicial exception because it exists in principle apart from any human action. The correlation itself (between OEC levels and skeletal disease) therefore cannot form the basis of eligibility.
As such, the diagnosis to which the claims are directed is itself a judicial exception which cannot form the basis of eligibility and cannot integrate the claims into a practical application because they are directed to performance of the judicial exception itself.
The claims further attempt to integrate the judicial exception into a practical application by integrating the judicial exceptions into a method of treatment. Regarding whether integration of the judicial exception into a method of treatment comprises integration of the judicial exception into a practical application, MPEP 2106.04(d)(2) provides the following: “One way to demonstrate such integration is when the additional elements apply or use the recited judicial exception to effect a particular treatment or prophylaxis for a disease or medical condition. The application or use of the judicial exception in this manner meaningfully limits the claim by going beyond generally linking the use of the judicial exception to a particular technological environment, and thus transforms a claim into patent-eligible subject matter. Such claims are eligible at Step 2A, because they are not “directed to” the recited judicial exception”. Regarding the particularity of the treatment step, the MPEP indicates that recitation of an abstract idea in conjunction with a step of, for example, “administering a suitable medication to a patient” does not integrate the judicial exception into a practical application because the treatment step is general (not particular) and is merely instruction to “apply” the judicial exception in a generic way.
As it applies to the instant case, claim 1 and its dependent claims 3-6 do not recite any actual treatment step, and therefore do not integrate the judicial exceptions into a particular treatment.
Claim 2 recites a treatment step at a high level of generality (“treating the subject for the skeletal disease”) wherein this treatment step is not particular enough to integrate the judicial exceptions into a practical application because the treatment step is general and is merely an instruction to apply the judicial exception in a generic way (i.e. the treatment step encompasses applying any kind of treatment for any kind of skeletal disease).
Dependent claims 3-6 provide further limitation on the type of skeletal disease, and the classification and identification of OECs, but none of these limitations serves to integrate the recited judicial exceptions into a practical application.
Neither the independent claim nor the additional limitations provided in the dependent claims are sufficient to either integrate the judicial exceptions into a practical application or to constitute “significantly more” than the recited judicial exceptions, because they amount to mere data gathering in support of the judicial exception (i.e. in order to diagnose the skeletal disease (abstract idea), one must gather data about OEC levels in a sample in order to apply the naturally occurring relationship between OEC levels and skeletal disease presence). Wherein mere data gathering in support of a judicial exception has been identified by the courts as insignificant extra solution activity which cannot constitute significantly more than the judicial exception. See MPEP 2106.05(g). Additionally, identifying and quantifying OECs is recited at a high level of generality and is not tied to any particular machine, apparatus, or specific procedure. See MPEP 2106.04(a)(2).
Furthermore, the detection of a biomarker in a biological sample has been identified by the courts to be routine and conventional activity in the life sciences arts (see MPEP 2106.05(d)(II)), and the specific measurement of OECs in a sample was known, routine, and conventional in the art before the effective filing date of the claimed invention, as demonstrated by Atkins et al (RANK Expression as a cell surface marker of human osteoclast precursors in peripheral blood, bone marrow, and giant cell tumors of bone. Journal of Bone and Mineral Research. September 2006. Vol. 21, No. 9, pages 1339-49.; IDS entered) and Ritchlin et al (US 2006/0275834 A1; IDS entered) which both teach identification and quantification of OECs in a sample based on detection of specific surface markers, wherein detection and quantification is carried out by routine and conventional methods in the art such as flow cytometry and FACS. As such, the art collectively indicates that identification and quantification of OEC in a sample was known in the art and was routine such that it had been performed by multiple different practitioners using routine and conventional methods which were well known to one of ordinary skill in the art.
For all these reasons, the claimed elements, when taken alone or in combination, fail to include additional elements that are sufficient to either integrate the judicial exceptions into a practical application or amount to significantly more than the judicial exceptions.
Claim Rejections - 35 USC § 102
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1, 2, and 5 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ritchlin et al (US 2006/0275834 A1; IDS entered).
Regarding claims 1 and 5, Ritchlin teaches a method comprising:
Identifying the presence of OECs in the subject and quantifying the number of circulating OECs in a sample from the subject, wherein OECs are detected by identification of cell surface markers (Par. 62: CD11b, CD14, CD51/61, and RANK are established markers of mononuclear OCP; Par. 95: obtaining a sample from the subject and assaying the number of OCPs in the sample, wherein an increase in OCP compared to a healthy control indicates an inflammatory joint disease in the subject; Par. 99: method comprises counting the number of cells comprising at least one to eight markers selected from a group comprising RANK, CD14, CD51/61). Wherein cells that enhance human osteoclastogenesis (i.e. osteoclast precursors (OCPs) in Ritchlin) and which are, for example, RANK+CD14+ are understood to be OECs (see specification Pg. 8, Ln. 7-11); and
Diagnosing a skeletal disease in the subject when an increase in OECs is detected as compared to a control (Par. 3: diagnosing and treating inflammatory joint disease; Par. 95: obtaining a sample from the subject and assaying the number of OCPs in the sample, wherein an increase in OCP compared to a healthy control indicates an inflammatory joint disease in the subject; Par. 51: condition diagnosed may be RA or PsA).
Regarding claim 2, Ritchlin further teaches the method comprising treating the subject for the skeletal disease (Par. 3: diagnose and treat; Par. 48: PsA patients treated with anti-TNF agents; Par. 51)
Claim Rejections - 35 USC § 103
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.
Claim 6 is rejected under 35 U.S.C. 103 as being unpatentable over Ritchlin et al (US 2006/0275834 A1; IDS entered), as applied to claim 1 above, and further in view of Lee et al (US 2014/0274953 A1).
Regarding claim 6, Ritchlin teaches the method of claim 1 as described above. Ritchlin further teaches that osteoclasts and osteoclast precursors are generally derived from populations of CD14+ monocytes (Par. 83; Par. 97: typically osteoclast precursor cell refers to a circulating monocyte/macrophage lineage cell capable of osteoblast directed differentiation into osteoclasts). Ritchlin further teaches that a panel comprising a variety of different surface expression markers can be used to identify and quantify populations of OECs (Par. 99: suitable markers with a well understood meaning in the art can include, for example, a molecule that is associated with a particular type of cell. It is also understood that markers can be assayed for their presence or absence, each of which can give information).
Regarding claim 6, Lee discloses a number of different biomarkers which can be used to classify and differentiate cell types in methods such as flow cytometry. Lee teaches specifically that CD14 is a marker that is commonly expressed on monocytes but which may also be expressed on granulocytes, and teaches that CD66b is a marker commonly expressed on granulocytes which is generally not expressed on monocytes (Par. 197; Par. 206). As such, these teachings indicate that CD66b- can be used to differentiate CD14+ monocytes and CD14+ granulocytes (wherein gating for CD66b- would exclude CD14+ granulocytes).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Ritchlin to further include CD66b- in the phenotype of OECs examined, such that the OEC phenotype comprises CD14+/RANK+/CD66b-. One would be motivated to make this modification because Ritchlin teaches that the osteoclasts and osteoclast progenitors which are of interest and which are quantified in the disclosed methods are generally monocyte derived (i.e. not associated with granulocytes). Since gating for CD14+ cells may include both monocytes and granulocytes, as taught by Lee, further gating for CD66b- cells within this population would ensure that the monocytes of interest are included in the quantification of OECs, while granulocytes are excluded, thereby refining the specificity and accuracy of OEC detection. One of ordinary skill in the art would have a reasonable expectation of success in making this modification because Ritchlin teaches that the panel of biomarkers used in the method may comprise additional biomarkers (such as CD66b) which are well known in the art and which may be used to differentiate different cell types and populations.
Subject Matter Free of Prior Art
Claims 3-4 and 7-8 are rejected as described in the 112(a), 112(b), and 101 sections above. However, the claims are noted to contain subject matter which appears to be free of the prior art (as best interpreted in light of the 112(b) rejections discussed above).
Regarding claims 3-4 and 8, the closest prior art is Atkins et al (RANK Expression as a cell surface marker of human osteoclast precursors in peripheral blood, bone marrow, and giant cell tumors of bone. Journal of Bone and Mineral Research. September 2006. Vol. 21, No. 9, pages 1339-49.; IDS entered) and Ritchlin et al (US 2006/0275834 A1; IDS entered).
Atkins teaches identification and quantification of OECs in a sample from a subject (Abstract: human PBMNCs, BMMNCs, and GCT cells were analyzed for reactivity with anti-RANK mAbs by flow cytometry in combination with hematopoietic lineage restricted markers. GCTs were also analyzed by immunofluorescence. CD14+ monocytoid cells were sorted by FACS based on their relative RANK expression and cultured under OC-forming conditions. Importantly, sorted CD14+RANKhi PBMNCs treated with recombinant RANKL and M-CSF gave rise to approximately twice the number of osteoclasts than RANKmid or RANKlow cells; Fig. 1; Pg. 1343, Col. 2, Par. 2-Pg. 1344, Col. 1, Par. 1; Pg. 1340, Col. 2, Par. 3 and Pg. 1341, Col. 2, Par. 1: identification and quantification of OECs (CD14+RANKhi cells) by flow cytometry and FACS). Wherein cells that enhance human osteoclastogenesis and are CD14+RANKhi are understood to be OECs (see specification Pg. 8, Ln. 7-11); and
Atkins further teaches that such identification and quantification of OECs may be important for the diagnosis and management of diseases such as osteoporosis (Pg. 1340, Col. 1, Par. 3: the accurate identification of RANK-expressing pre-OCs in PB may have important clinical applications in the diagnosis and management of diseases characterized by increased bone resorption, such as osteoporosis).
Atkins differs from the instant claims in that the disclosed method only comprises identification and quantification of OECs in healthy control patients. Thus Atkins does not provide data that demonstrates that osteoporosis or osteopenia could be definitively diagnosed based on the level of OEC measured in a sample from a subject being higher than the level of OECs in a control. Atkins does not provide showing or teaching that definitively supports that OEC levels would be higher in a subject with osteoporosis or osteopenia as compared to a healthy control.
Regarding claim 7, the closest prior art is Ritchlin et al (US 2006/0275834 A1; IDS entered) in view of Lee et al (US 2014/0274953 A1) as described in the 103 rejection of claim 6 above. Ritchlin in view of Lee teaches that OECs may have the phenotype CD14+/RANK+/CD51/CD61+/CD66b- (Ritchlin Par. 99). Neither Ritchlin nor Lee specifically teaches that the OEC phenotype further comprising CCR2+/C3AR+/HLADR+.
Though these additional biomarkers are known in the art, the prior art does not contain teachings which would make it obvious to one of ordinary skill in the art to quantify OECs in the method of Ritchlin based on this particular phenotype comprising this particular combination of biomarkers.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ELLIS LUSI whose telephone number is (571)270-0694. The examiner can normally be reached M-Th 8am-6pm ET.
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/ELLIS FOLLETT LUSI/Examiner, Art Unit 1677
/CHRISTOPHER L CHIN/Primary Examiner, Art Unit 1677