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 .
Claims Status
Claims 1-19 are pending and are examined on the merits.
Specification
The disclosure is objected to because of the following informalities:
The third-to-last line of ¶0039 on Pg. 11 of the specification recites the same SEQ ID NO for successive CDRs: “CDR-H1 of SEQ ID NO: 7, CDR-H2 of SEQ ID NO 7...”. However, earlier in the same paragraph CDR-H1 is stated to correspond to SEQ ID NO: 6, which appears to be the correct CDR-H1 sequence.
Pg. 32, Example 4 references “Figure 4”, “Figure 3B”, and “Figure 4C”. However, there is no “Figure 3B” or “Figure 4C”, neither does the content of the figures appear to match the descriptions in Example 4. For example, in the § BRIEF DESCRIPTION OF THE FIGURES, Figure 4 is described as: “a graph showing the quantification of HA fragments in cytokine-treated Hyal2+ cells” (¶0018), whereas Example 4 references cells isolated from peripheral blood and stained with anti-Hyal2 antibodies (¶0095).
Pg. 33, Example 6 references “Figure 6C”, “Figure 6D”, and “Figure 6E” – however no such figures exist in the instant disclosure.
Appropriate correction is required.
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, 10-14, and 18-19 are rejected under 35 U.S.C. 101 because the claimed invention is directed to natural phenomenon without significantly more.
The claims recite: “detecting a level of hyaluronidase 2-positive myeloid cells...wherein an elevated level of hyaluronidase 2-positive myeloid cells in the blood sample identifies the subject as suffering from cancer” (Claims 1-6, 10-11); “detecting an elevated level of hyaluronidase 2-myeloid cells” (Claims 12-18); or “detecting a level of hyaluronidase 2-positive myeloid cells...wherein a decreased level of hyaluronidase 2-positive myeloid cells...is indicative of effective treatment” (Claim 19).
In each case, the claims are directed to the naturally occurring correlation between hyaluronidase 2-positive myeloid cells and the presence of cancer in an individual, which constitutes the judicial exception of a “natural phenomenon”.
This 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 because:
Regarding Claims 1-6, the sole active step of the claimed method is “detecting a level of hyaluronidase 2-positive myeloid cells”. Dependent Claims 10-11 specify the types of cancer, and dependent claims 2-5 are drawn to particular subpopulations of cells and additional biomarkers – each themselves natural phenomenon inherent to the measured cell population. Dependent Claim 6 specifies the Hyal2 binding agent as a generic “antibody”.
Well-understood, routine and conventional limitations are not enough to qualify the claimed method as reciting something “significantly more” than the judicial exception(s) (see MPEP 2106.04(d)). In the instant case, “detecting” protein expression is a data gathering step necessary to observe the natural phenomenon, and methods of detecting expression levels with an antibody are routine and conventional for one of ordinary skill in the art. For example, Albeiroti et al. 2015 (Blood, 125(9), 1460-1469.; PTO-892) employs anti-HYAL2 antibodies in a variety of well-known assays including flow cytometry, western blot, and immunofluorescence to detect the presence of HYAL2 on isolated platelet cells (Fig. 4-5).
Further, regarding Claims 12-14, each claim requires the additional step of “administering a cancer therapy” in the generic without any particular therapeutics. Claim 18 further specifies broad categories of cancer therapies comprising “radiotherapy, chemotherapy or immunotherapy”. However, in order for a treatment to satisfy “Step 2A Prong Two” in determining patentability, treatment limitations must be “particular” and “have more than a nominal or insignificant relationship to the exception(s)”. See MPEP 2106.04(d)(2).
The judicial exception encompassed by Claims 12-14 and 18 (correlation between HYAL2 myeloid cells and cancer) is not integrated into the treatment method such that it modifies or improves the “cancer therapy”, which is otherwise conventional and routine – including the broad recitation of “radiotherapy, chemotherapy or immunotherapy” of Claim 18, each of which is listed as among the “most common types of treatment for cancer” by the American Cancer Society (http://www.cancer.org/treatment/; captured online 05/2020; PTO-892). The step of “detecting an elevated level of hyaluronidase 2-myeloid cells” would not in itself provide any therapeutic benefit, and the claimed observation of said cells does not directly limit or modify the claimed “cancer therapy” such that the judicial exception is integrated into a particular and practical application.
Regarding Claim 19, the sole active step recited is “detecting a level of hyaluronidase 2-positive myeloid cells”, directed to observing a natural phenomenon. The claim further recites an additional natural phenomenon/judicial exception “wherein a decreased level of hyaluronidase 2-positive myeloid cells...is indicative of effective treatment”, drawn to the naturally occurring correlation between hyaluronidase 2-positive cells and treatment response. The judicial exceptions of the claim are not integrated into a practical application because the claim recites no particular or affirmative action or application of the level of hyaluronidase 2-positive myeloid cells or observation thereof.
Claim Rejections - 35 USC § 112
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 1-18 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.
Claim 1 is drawn to a method of diagnosing cancer comprising the limitation “...an elevated level of hyaluronidase 2-positive myeloid cells...”, and Claim 12 is drawn to a method of treating cancer comprising the step “detecting an elevated level of hyaluronidase 2-myeloid cells in a blood sample”. However, the metes and bound of the term “elevated” are unclear (e.g. elevated proportion of cells? elevated number of cells? elevated levels of hyaluronidase 2? Etc.). Moreover, it is unclear what particular numbers, proportions, or hyaluronidase 2 levels would be considered “elevated”, and the claims provide no point reference for comparison (i.e., elevated compared to what?). Claims 2-11 and 13-18 which depend from Claims 1 or 12 are rejected for the same reasons.
Claim 12 is further rejected because it is unclear what is meant by the term “hyaluronidase 2-myeloid cells” as this term is neither standard in the art nor is it expressly defined in the instant specification. For the purposes of examination, “hyaluronidase 2-myeloid cells” are interpreted to refer to “hyaluronidase 2-positive myeloid cells” as recited in ¶0074 of the instant specification.
Claims 7 and 15 each recite an antibody comprising “a set of 6 CDRs set forth in SEQ ID NOs: 6-11”. However, the claims do not specify which particular CDR (CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, or CDR-L3) corresponds to which SEQ ID NO, and it is therefore unclear if the antibody is intended to be encompassed by the claims. For the purposes of examination, the CDRs of SEQ ID NOs: 6-8 are interpreted to correspond to CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, or CDR-L3, respectively, as defined at ¶0039 of the instant specification.
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 7-9 and 15-17 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a written description rejection.
Scope of the claims
Each of claims 7-9 and 15-17 encompass antibodies defined functionally by their binding to hyaluronidase 2. The antibodies of Claims 8-9 and 16-17 are further defined only by partial structure, reciting a VH or VL sequence, allowing for unlimited possible pairing with unspecified VH or VL sequences.
State of the relevant art
Antibodies that bind HYAL2 and their utility in determining HYAL2 levels are known in the art (see, for example, Albeiroti et al. 2015 Blood, 125(9), 1460-1469.; PTO-892), however antibodies comprising the instantly claimed sequences are not. As was well known in the antibody art, the formation of an intact antigen binding site in a conventional antibody typically requires the association of the complete heavy and light chain variable regions of a given antibody, each of which comprises three CDRs (or hypervariable regions) which provide the majority of the contact residues for the binding of the antibody to its target epitope (reviewed in Sela-Culang et al. Frontiers in Immunology 4 (2013): 302.; PTO-892). It is generally understood that all six CDRs in combination and in a specific order (HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, LCDR3) are required to convey an antibody’s specificity to its target, and that neither the CDRs themselves nor individual VH and VL domains are interchangeable.
For example, Julien 2017 (US 2017/0355756 A1; PTO-892) discloses an antibody specific for human TDP-43 with a heavy chain comprising 3 CDRs termed “C10-VH3” (Table A, SEQ ID NO. 4). Cassone 2008 (WO 2008/068048 A2; PTO-892) discloses an antibody with a heavy chain comprising the same 3 CDRs (“αSAP 2A8”; Pg. 18, SEQ ID NO. 2). However, the antibody of Cassone 2008 is paired with a different VL and targets an entirely different protein – secreted aspartyl protease (SAP) from pathogenic yeast in the genus Candida sp. Below is an alignment between the VH domains of these unrelated antibodies; the 3 HCDRs according to Julien 2017 are highlighted (SEQ ID NOs: 16-18):
C10-VH3 15 RKLSCAASGFTFSSFGMHWVRQAPEKGLEINVAYISSGSSTLHYADTVKGRFTISRDNPK 74
||||||||||||||||||||||||||||| |||||||||||||||||||||||||||||
αSAP 2A8 1 RKLSCAASGFTFSSFGMHWVRQAPEKGLEW-VAYISSGSSTLHYADTVKGRFTISRDNPK 59
C10-VH3 75 NTLFLQMKLPSLCYGLLGPRDHGH 98
|||||||||||||||||| |: |
αSAP 2A8 60 NTLFLQMKLPSLCYGLLGSRNLSH 83
Sela-Culang further teaches that antigens lack intrinsic properties that clearly differentiate between epitopic and non-epitopic residues, and any part of the antigen surface my become part of an epitope under some circumstances (“Ab Epitope Prediction”; Pg. 2). In the same vein, Edwards et al. 2003 (Journal of molecular biology 334.1 (2003): 103-118.; PTO-892) endeavored to uncover the breadth of the structural diversity of antibodies a single antigen can give rise to.
Edwards employed a phage display library to screen for antibodies that bind a single protein, BLyS, and isolated over 1000 unique anti-BLyS antibodies, each comprising a different amino acid sequence (Abstract). These antibodies were structurally diverse, resulted from nearly all possible Vh, D, and Jh, germlines (Pg. 105; “Vh and Vl germline usage”), and comprised 568 distinct Vh CDR3 sequences, ranging in length from 5 to 25 amino acid residues (Fig. 4; “Vh CDR3 sequence diversity”; Pg. 105). Together, these works highlight that neither knowledge of the antigen sequence nor the antibody sequence is necessarily predictive of its function.
Description of representative species in the specification
MPEP § 2163 states that a “representative number of species” means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.
In the instant case, however, the specification discloses but a single structurally defined species of antibody purportedly belonging to the claimed genus comprising both a VH comprising SEQ ID NO: 4 and VL comprising SEQ ID NO: 2 – which comprise the CDRs of SEQ ID NOs 6-8 and 9-11, respectively (¶0041). Accordingly, one of ordinary skill in the art would not reasonably consider a single species of antibody representative of the nearly unlimited potential species comprising the claimed VH or VL.
Identifying characteristics and structure/function correlation
In the absence of a representative number of species, the written description requirement for a claimed genus may be satisfied by disclosure of relevant, identifying characteristics; i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. To meet this requirement in the instant case, the specification must describe structural features that the skilled artisan as of the effective filing date would have expected to convey the claimed binding activity.
However, the specification discloses no structure/function relationship between the claimed sequences and their ability to bind HYAL2, and there is no discussion of which residues are important for said interaction or whether the VH or VL are alone sufficient to confer the required HYAL2 binding activity.
Further, regarding Claims 7 and 15, each claim requires a complete set of 6 defined CDR sequences. However, as discussed above, there no way to determine a priori from any given antibody sequence what its target antigen may be, and the disclosure fails to demonstrate any functional properties of the claimed antibodies. Each of the examples appear to make use of commercially available polyclonal HYAL2 antibody (¶0079), and there is no direct showing that an antibody comprising the claimed sequences binds to HYAL2.
Absent a disclosure of evidence that an antibody comprising instantly claimed CDRs according to SEQ ID NOs: 6-11 possesses the required function of binding HYAL2, applicant has not conveyed to one of ordinary skill in the art that they were in possession of the claimed invention.
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.
The factual inquiries 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 nonobviousness.
Claims 1-6, 10, and 12-14 are rejected under 35 U.S.C. 103 as being unpatentable over Yang et al. 2015 (International journal of cancer, 136(8), 1845-1855.; PTO-892), herein “Yang”, in view of Albeiroti et al. 2015 (Blood, 125(9), 1460-1469.; PTO-892), herein “Albeiroti”, and as evidenced by the instant specification.
Yang teaches that reduced HYAL2 methylation levels in peripheral blood samples can be used to diagnose breast cancer (Abstract; Table 1; § “What’s new?”).
Yang teaches there is an inverse correlation between HYAL2 expression and DNA methylation, wherein peripheral blood leukocytes having reduced methylation levels express greater amounts of HYAL2 (Fig. 3; Pg. 136 § The inverse correlation between the methylation and expression of HYAL2 in peripheral blood leukocytes).
Yang teaches that HYAL2 methylation levels were lower in leukocytes depleted of B and T cells (Fig. 4), which comprised “mainly granulocytes, monocytes, and NK cells” (Pg. 136, §1). Both granulocytes and monocytes are “myeloid cells” as evidenced by the instant specification (¶0021).
Further, regarding claims 3-5, Yang is silent on whether the peripheral blood myeloid cells further expressed CD11b, HLA-DR, or CD14. However, the presence or absence of said markers are inherent to hyaluronidase-2 positive myeloid cells as evidenced by the instant specification (¶0021; ¶0095; ¶0098).
Yang does not teach that the HYAL2 levels are detected with an anti-HYAL2 antibody. This deficiency is cured by Albeiroti.
Albeiroti teaches that HYAL2-positive platelet cells collected from a blood sample are detected by contacting the cells with an anti-HYAL2 antibody, and that the antibody can be used to quantitate the fold-increase in surface HYAL2 in cells compared to a control (Fig. 4; Supplement § Platelet Isolation, Immunohistochemical staining of platelets).
It would have been obvious to one of ordinary skill in the art that the method of detecting cancer by measuring HYAL2 methylation in peripheral blood taught by Yang could alternatively be accomplished by detecting HYAL2-positive cells with an anti-HYAL2 antibody according to the teachings of Albeiroti – which constitutes a simple substitution of one well known technique for another in order to achieve the same results (See MPEP § 2143(I)). There would have been a reasonable expectation of success because Yang teaches reduced HYAL2 methylation correlates with increased HYAL2 expression, and because Albeiroti teaches that antibodies can be used to measure increases in HYAL2 protein levels in cells collected from blood.
Further, regarding Claims 12-14, Yang is silent on whether the breast cancer patients were further administered a cancer therapy.
However, Yang additionally teaches monitoring HYAL2 “could serve as a blood-based marker for early breast cancer detection” and “[a]lthough therapeutic advances have improved the survival rate, most BC patients still suffer from greatly reduced quality of life and even metastasis owing to inefficient risk evaluation or delayed diagnosis”.
It would have been obvious to one of ordinary skill in the art that the method of diagnosing breast cancer by detecting elevated HYAL2 with a HYAL2 antibody taught by Yang in view of Albeiroti should be followed by administering a cancer therapy to the patient. The skilled artisan would have been motivated by the suggestion of Yang that delayed diagnosis results in metastasis and reduced quality of life – implying that earlier treatment results in improved outcomes. There would have been a reasonable expectation of success because Yang teaches HYAL2 can be used to detect breast cancer in its early stages.
Claim 18 is rejected under 35 U.S.C. 103 as being unpatentable over Yang et al. 2015 (International journal of cancer, 136(8), 1845-1855.; PTO-892), herein “Yang”, and Albeiroti et al. 2015 (Blood, 125(9), 1460-1469.; PTO-892), herein “Albeiroti”, as applied to Claims 1-6 and 19 above, and further in view of American Cancer Society Treatment Types (http://www.cancer.org/treatment/; captured online 05/2020; PTO-892), herein “ACS”.
The teachings of Yang and Albeiroti are summarized above.
Yang and Albeiroti do not teach that the treatment comprises chemotherapy, radiation, or immunotherapy. This deficiency is cured by ACS.
ACS teaches that chemotherapy, radiation therapy, and immunotherapy are among the “most common types of treatment for cancer” (§ Types of Cancer Treatment).
It would have been obvious to one of ordinary skill in the art that the method detecting HYAL2 and of treating cancer according to the combined teachings of Yang or Albeiroti could comprise chemotherapy, radiation, or immunotherapy. The skilled artisan would have been motivated to choose these treatment modalities – and there would have been a reasonable expectation of success – because ACS teaches that they are among the most common types of treatment for cancer.
Statutory Double Patenting
A rejection based on double patenting of the “same invention” type finds its support in the language of 35 U.S.C. 101 which states that “whoever invents or discovers any new and useful process... may obtain a patent therefor...” (Emphasis added). Thus, the term “same invention,” in this context, means an invention drawn to identical subject matter. See Miller v. Eagle Mfg. Co., 151 U.S. 186 (1894); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Ockert, 245 F.2d 467, 114 USPQ 330 (CCPA 1957).
A statutory type (35 U.S.C. 101) double patenting rejection can be overcome by canceling or amending the claims that are directed to the same invention so they are no longer coextensive in scope. The filing of a terminal disclaimer cannot overcome a double patenting rejection based upon 35 U.S.C. 101.
Claims 1 and 12-18 are provisionally rejected under 35 U.S.C. 101 as claiming the same invention as that of claims 1 and 12-18 of copending Application No. 18/912,748 (reference application).
Each of claims 1 and 12-18 in both the instant application and copending application ‘748 recite identical language encompassing identical inventions. This is a provisional statutory double patenting rejection since the claims directed to the same invention have not in fact been patented.
Pursuant to 37 CFR 1.78(f), when two or more applications filed by the same applicant or assignee contain patentably indistinct claims, elimination of such claims from all but one application may be required in the absence of good and sufficient reason for their retention during pendency in more than one application. Applicant is required to either cancel the patentably indistinct claims from all but one application or maintain a clear line of demarcation between the applications. See MPEP § 822.
Nonstatutory Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claim 19 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 12-18 of copending Application No. 18/912,748 (reference application), as evidenced by the instant specification. Although the claims at issue are not identical, they are not patentably distinct from each other because:
‘748 claim 1 is identical to instant claim 1 and is drawn to a method of diagnosing cancer comprising detecting an elevated level of hyaluronidase 2 positive myeloid cells “wherein an elevated level of hyaluronidase 2-positive myeloid cells...identifies the subject as suffering from cancer”.
Regarding instant claims 6-9, ‘748 claims 13-17 are drawn to a method of treating cancer comprising a step of detecting elevated hyaluronidase 2-positive myeloid cells by means of contacting a blood sample with an anti-hyaluronidase 2 antibody comprising the same sequences of instant claims 7-9.
Regarding instant claims 3-5, the claims of ‘748 are silent on CD11b, HLA-DR, CD14 and expression. However, the presence or absence of said markers are inherent to hyaluronidase-2 positive myeloid cells as evidenced by the instant specification (¶0021; ¶0095; ¶0098).
Regarding instant claim 19, the claims of ‘748 are not drawn to a method of “monitoring efficacy of treatment” wherein “a decreased level of hyaluronidase 2-positive myeloid cells...is indicative of effective treatment”.
However, it would have been obvious to one of ordinary skill in the art that the method of diagnosing cancer of ‘748 and instant claim 1 could be adapted for the purposes of monitoring treatment efficacy. The skilled artisan would have recognized that because the claims establish a correlation between increased hyaluronidase 2-positive myeloid cells and the presence of cancer, it would follow that decreased hyaluronidase 2-positive myeloid cells correlates with a reduced cancer presence – which would be indicative of effective treatment. There would have been a reasonable expectation of success because the claims require the same active step of “detecting a level of hyaluronidase 2-positive myeloid cells” and each relies on observing the same correlation between hyaluronidase 2-positive myeloid cells and cancer status.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 2 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 12-18 of copending Application No. 18/912,748 in view of Yang et al. 2015 (International journal of cancer, 136(8), 1845-1855.), herein “Yang”. Although the claims at issue are not identical, they are not patentably distinct from each other because:
The claims of ‘748 are summarized above
Regarding instant Claim 2, the claims of ‘748 do not specify that the blood sample is a peripheral blood sample. This deficiency is cured by Yang.
Yang teaches that peripheral blood samples can be used to diagnose early-stage cancer by detecting a decrease in HYAL2 DNA methylation patterns (Abstract; Table 1; Fig. 1), which correlates with increased HYAL2 expression (Fig. 3).
It would have been obvious to one of ordinary skill in the art that the blood sample of the claims of ‘748 could be a peripheral blood sample. There would have been a reasonable expectation of success because Yang teaches that increased HYAL2 expression in the peripheral blood correlates with increased risk of cancer.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claim is allowed.
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/BRYAN WILLIAM HECK/Examiner, Art Unit 1643
/GARY B NICKOL/Primary Examiner, Art Unit 1643