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 .
Election/Restrictions
Applicant’s election without traverse of Group II, claims 15-22 is acknowledged.
Claims 1-14 withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 July 31, 2025.
Claim 23 is added.
Claims 15-23 are examined below.
Claim Objections
Claims 15 and 19-22 are objected to because:
Claims 15, 19, and 20 contain abbreviations C2C, CTX-I, CTX-II, RANKL, PIICP, COMP and PINP. Claim 21 contains abbreviations C2C, CTX-I, CTX-II, and RANKL. Claim 22 contains abbreviations C2C, COMP, PIICP, CTX-II, and RANKL. Abbreviations should be completely spelled out in its first occurrence.
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 15-23 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter. The claims do not fall within at least one of the four categories of patent eligible subject matter because claim 15 recites a biomarker profile “comprising polypeptide concentration levels” which is a claim to “mere information in the form of data.”
For these reasons, claims 15-23 fail patent subject matter eligibility criteria.
Further, these claims may be interpreted as encompassing a biological fluid, such as urine or blood. The following analysis addresses this embodiment:
Claims 15-23 are rejected under 35 U.S.C. 101 because the claimed invention is directed to natural product without significantly more.
The claims recite “a predictive biomarker comprising polypeptide concentration levels.” This encompasses blood or a urine sample, for example, which are natural products. An appropriate characteristic that must be possessed by both blood and urine samples is to maintain the polypeptide biomarkers at the concentration levels identical to those naturally present in blood or urine of the canine subjects. The samples as claimed are not subjected to processing steps that would change the nature and the appropriate characteristic of these bodily fluids prior to the biomarker analysis. Therefore, the blood or urine samples of claims 15-23 lack markedly different characteristic from their nature-based counterparts of blood and urine, and are products of nature exception (MPEP 2106.04(c)).
The claims also recite the relationship between the biomarker and susceptibility to having and/or developing canine hip dysplasia which is a naturally occurring correlation between the levels of specific protein biomarkers and detection, prediction and/or diagnose of hip dysplasia. This relationship is categorized as a naturally occurring correlation, and therefore it is a judicial exception.
This judicial exception is not integrated into a practical application because claims 15-23 fail to recite significantly more than a judicial exception. The claims recite only the biomarker profiles in canine subjects without providing any additional steps of using the profiles in a treatment or care of the animals.
The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claims fail to recite any element, or combination of elements, sufficient to ensure that the claims amount to significantly more than the exception.
For all of these reasons, claims 15-23 are ineligible under 35 U.S.C. 101.
Claim Rejections - 35 USC § 112
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 15-23 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 enablement requirement. The claims contain subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
Enablement requires that the specification teach those in the art to make and use the invention without undue experimentation. The factors to be considered in determining whether a disclosure meets the enablement requirements of 35 U.S.C. 112, first paragraph, have been described in In re Wands, 858 F.2d 731, 8 USPQ2d 1400 (Fed. Cir., 1988). The court in Wands states, “Enablement is not precluded by the necessity for some experimentation, such as routine screening. However, experimentation needed to practice the invention must not be undue experimentation. The key word is ‘undue’, not ‘experimentation’” (Wands, 8 USPQ2sd 1404). Clearly, enablement of a claimed invention cannot be predicated on the basis of quantity of experimentation required to make or use the invention. “Whether undue experimentation is needed is not a single, simple factual determination, but rather is a conclusion reached by weighing many factual considerations” (Wands, 8 USPQ2d 1404). Factors to be considered in determining whether a disclosure would require undue experimentation include (1) the nature of the invention, (2) the state of the prior art, (3) the predictability or lack thereof in the art, (4) the amount of direction or guidance present, (5) the presence or absence of working examples, (6) the quantity of experimentation necessary, (7) the relative skill of those in the art, and (8) the breadth of the claims.
(1) The nature of the invention.
The present disclosure claims a predictive biomarker profile comprising polypeptide concentration levels for polypeptides selected from the group consisting of: C2C, CTX-1, CTX-11, RANKL, PIICP, COMP, PINP, and fragments (e.g., portion of the full protein structure) of any thereof, and any combination thereof. The invention sets forth that the biomarker must be “predictive” and thus, the biomarker must in some way be indicative of the phenotype of “susceptible to having and/or developing CHD.”
(2) The state of the prior art.
The closest prior art reference of Bozynski et al. (“ROC curve analysis of protein biomarkers in serum and urine for diagnosis of hip dysplasia.” 2017 Annual Meeting of the Orthopaedic Research Society. San Diego, CA, United States. 19 Mar 2017-22 Mar 2017, Journal of Orthopaedic Research, (March 2017) Vol. 35, Supp. Supplement 1. Abstract Number: 0574), teaches ROC curve analysis of C2C, CTX-1, CTX-11, RANKL, PIICP, COMP, PINP biomarkers in serum and urine for diagnosis of hip dysplasia, but fails to provide relevant biomarker concentrations needed to practice the invention. Art is silent on biomarkers with predictive features for hip dysplasia.
(3) The predictability or lack thereof in the art.
The subject matter of protein biomarker analysis for diagnostic purposes is highly unpredictable, because of the lack of standardization in the art, and the absence of established, art recognized biomarkers or their combinations. Therefore, it is not sufficient for the Applicant to recite a number of analyzed biomarkers without reciting specific concentration ranges and providing evidence that the biomarkers have claimed predictive capability. The unpredictability in the art is exemplified in the data disclosed in the instant application, as discussed further in section (4) of this rejection.
(4) The amount of direction or guidance presented and (5) the presence or absence of working examples.
The specification fails to provide relevant biomarker concentration ranges and their differences that can be used for predicting hip dysplasia. Additionally, the instant specification fails to provide adequate guidance to enable one skilled in the art to identify the relevant predictive concentration ranges.
For example, Fig. 1-7 and 9-15 illustrate the biomarker concentration levels monitored in healthy dogs and dogs with dysplastic hips for 24 months. For biomarkers C2C, CTX-I, CTX-II, and RANKL in urine samples there is some difference in biomarker levels at 5 months’ time point between healthy dogs and dogs with dysplastic hips. However, the presented evidence fails to satisfy basic requirements for biomarker evidence, because if a biomarker is suitable for differentiating healthy dogs from dogs with dysplasia at the age of 5 months, the same biomarker should work at other time points. Biomarkers C2C, CTX-I, CTX-II, and RANKL in urine fail to follow the 5 month’s patterns at other time points. C2C biomarker even reverses the pattern at the next time point (6 months), which clearly indicates its unsuitability to serve as a differentiating biomarker as disclosed in the instant specification. All claimed biomarkers: C2C, CTX-1, CTX-11, RANKL, PIICP, COMP, PINP fail to show consistent concentration patterns from one time point to another.
The demonstrated differences between CTX-I, CTX-II and RANKL biomarker concentration levels in healthy and dysplasia dogs show significant overlaps and Applicant fails to disclose appropriate statistical analysis of these results to show that the observed differences of the biomarker levels in healthy and dysplasia dogs are indeed significant.
The claims recite “predictive biomarker profile”. However, the instant specification fails to demonstrate results illustrating the predictive power of the biomarker profiles.
To summarize, the results presented in the specification fail to provide evidence that the claimed profiles are suitable for use as diagnostic and predictive profiles.
(6) The quantity of experimentation necessary.
Considering the immature state of the art and the lack of specific concentration ranges for claimed biomarkers in the specification, one of ordinary skill in the art would be burdened with undue experimentation to use the claimed panel for predicting or diagnosing hip dysplasia in dogs.
(7) The relative skill of those in the art.
The relative skill of those in the art is high with an ordinary practitioner possessing a PhD and related post-doctoral research experience.
(8) the breadth of the claims.
The breadth of the claims is substantial. Applicant claims canines as a broad group of animals, but only dogs were actually used in the disclosed example.
Following all of this, one skilled in the art could not practice the invention of claims 15-23 without undue experimentation. One would have to repeat the entire study to obtain data necessary for performing diagnosis using claimed biomarkers. Moreover, one of ordinary skill in the art would have no reasonable expectation of success of experimenting with the claimed biomarkers. Therefore, claims 15-23 are rejected under 35 U.S.C. 112(a).
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 15-23 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 15-23 recite predictive biomarker profile. It is unclear what is actually claimed, information about protein biomarkers comprising the profile or a composition of matter. The specification fails to provide sufficient details about the structure of the profile including concentration levels, ranges, or cut-off values for healthy dogs and dogs with dysplasia.
Claim 15 contains “e.g.” which renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. The claim also contains parenthetical subject matter which is vague because it is unclear if the parenthetical subject matter are positive limitations of the claim.
Claim Rejections - 35 USC § 102
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 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.
(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 15-23 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Bozynski et al. (“ROC curve analysis of protein biomarkers in serum and urine for diagnosis of hip dysplasia.” 2017 Annual Meeting of the Orthopaedic Research Society. San Diego, CA, United States. 19 Mar 2017-22 Mar 2017, Journal of Orthopaedic Research, (March 2017) Vol. 35, Supp. Supplement 1. Abstract Number: 0574).
Regarding claims 15-16 and 23, Bozynski teaches “ROC curve analysis of protein biomarkers in serum and urine for diagnosis of hip dysplasia” (Title) and “The objective of the present study was to identify protein biomarkers with high discriminatory capabilities for differentiating dysplastic dogs from non-dysplastic dogs” (2nd paragraph, Introduction). Bozynski also teaches canine hip dysplasia (CHD) biomarker profile comprising polypeptide concentration levels for two or more polypeptides selected from the group consisting of: C2C, CTX-I, CTX-II, RANKL, PIICP, COMP, PINP, and fragments (e.g., portion of the full protein structure) of any thereof, and any combination thereof, obtained from a biological sample from at least one healthy canine subject and at least one canine subject susceptible to having and/or developing CHD.
The instantly rejected claims do not distinguish the claimed profile from the profile set taught by the reference. The claim sets forth that the profile is “polypeptide concentration levels” for the recited polypeptides, and Bozynski teaches this. The fact that the claim states that the levels are “obtained from a biological sample from at least one skeletally immature canine subject” does not distinguish the profile of the prior art from the current profile, since the data in the instant specification clearly demonstrate that profiles form immature and mature animals susceptible to hip dysplasia overlap.
Furthermore, regarding the limitation that the profiles are “predictive” the reference teaches that the biomarkers have high discriminatory ability. Neither the instant specification nor the instant claims provide any structural feature of the claimed profile that distinguishes it from the concentrations taught in the prior art.
Regarding claims 17-18, Bozynski teaches the types of samples collected from the dogs for detection of hip dysplasia biomarkers “serum and urine were aliquoted into separate tubes and stored at -80°C until analyzed” (Methods).
Regarding claims 19-20, Bozynski teaches biomarkers comprising polypeptides C2C, COMP, PIICP, CTX-I, CTX-II, and RANKL (Methods), meeting the limitations of claim 19 for three or more polypeptides and claim 20 for four or more polypeptides selected from the group consisting of C2C, CTX-I, CTX-II, RANKL, PIICP, COMP, PINP.
Regarding claims 21-22, Bozynski teaches the biomarker profile of claim 15, comprising polypeptide concentration levels of each of C2C, CTX-I, CTX-II, and RANKL, wherein the sample is a urine sample, and C2C, COMP, PIICP, CTX-II and RANKL, wherein the sample is a serum sample. Specifically, Bozynski teaches “Cartilage oligomeric matrix protein (COMP), cross linked C telopeptide of type I, II collagen (CTX-I, CTX-II), receptor activator of nuclear factor kappa-B ligand (RANKL), tissue inhibitor of metalloproteinase 1 (TIMP-1), procollagen type I N-terminal propeptide (PINP), procollagen type IIA N-terminal propeptide (PIIANP), collagenase-generated cleavage epitope of type II collagen (C2C) and procollagen type II C-terminal propeptide (PIICP) concentrations in serum and urine were measured using commercially available enzyme-linked immunosorbent assays (ELISA) according to the manufacturer's instructions” (Results).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Alexander Volkov whose telephone number is (571) 272-1899. The examiner can normally be reached M-F 9:00AM-5:00PM (EST).
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Bao-Thuy Nguyen can be reached on (571) 272-0824. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ALEXANDER ALEXANDROVIC VOLKOV/
Examiner, Art Unit 1677
/REBECCA M GIERE/Primary Examiner, Art Unit 1677