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 .
Continued Examination Under 37 CFR 1.114
2. A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 13 May 2026 has been entered.
3. Applicant's arguments and amendments to the claims presented in the reply of 13 May 2026 have been fully considered but do not place the application in condition for allowance. All rejections and objections not reiterated herein are hereby withdrawn.
In particular, the previous rejection of claims 1, 3-8, 14 and 16 under 35 U.S.C. 101 has been obviated by the amendment to recite the final step of “administering at least one an agent selected from one or more of a PGE synthetic agonist, an oral steroid, an anti-IgE, a β1 agonist, a β2 agonist, a mast cell stabilizer, a leukotriene antagonist, Ipratropium bromide, and a phosphodiesterase inhibitor to the subject having a predisposition for asthma” and by the cancellation of claims 3 and 4.
The previous rejection of claims 21 and 22 under 35 U.S.C. 112(b) has been obviated by the amendment to claims 21 and 22 to include the limitation of “wherein the presence of the one or more SNPs in the subject has been determined by assaying a nucleic acid sample from the subject.”
The previous rejection of claims 21 and 22 under 35 U.S.C. 102(a)(1) as being anticipated by Gould et al has been obviated by the amendment to claims 21 and 22 to include the limitation of “wherein the presence of the one or more SNPs in the subject has been determined by assaying a nucleic acid sample from the subject.”
Claim Status
4. Claims 1, 2, 5-8, 14-16, 21, 22, and 24-27 are pending.
Claims 2, 15 and 24-27 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Note that Applicant elected Group I and the species of rs2529168 without traverse in the reply of 25 June 2025.
Claims 1, 5-8, 14, 16, 21, and 22 read on the elected invention and have been examined herein. It is noted that the claims encompass the non-elected species of SNPs other than rs2529168 and non-elected combinations of SNPs. Prior to the allowance of claims, any non-elected subject matter which has not been rejoined with the elected subject matter will be required to be removed from the claims.
New Claim Objections
5. Claims 14, 16, 21 and 22 are objected to because of the following informalities:
Claim 14, and thereby dependent claim 16, recites “detecting the presence of at least one single nucleotide polymorphism (SNP), a G allele in rs2529168 in a nucleic acid sample” whereas the claim should recite “detecting the presence of at least one single nucleotide polymorphism (SNP) which is a G allele in rs2529168 in a nucleic acid sample” or “detecting the presence of a G allele in rs2529168 in a nucleic acid sample.”
Claim 21, and thereby dependent claim 22, are objected to because the claims refer interchangeably to a patient and to a subject, whereas the claims should refer to only a patient or to only a subject.
Appropriate correction is required.
New Objection to the Specification
6. The amendment filed 16 March 2026 is objected to under 35 U.S.C. 132(a) because it introduces new matter into the disclosure. 35 U.S.C. 132(a) states that no amendment shall introduce new matter into the disclosure of the invention. The added material which is not supported by the original disclosure is as follows: the recitation of the specific alleles at each of the SNPs – i.e., “a G allele in rs2529136, an A allele in rs2429063, a G allele in rs2529155, a G allele in rs2529168, an A allele in rs2700292, a T allele in rs2700296, a G allele in rs10267234, an A allele in rs150512506, a G allele in rs28840812, a C allele in rs111933649, and a G allele in rs78748801.”
The disclosure as originally filed teaches the SNPs of rs2529136, rs2429063, rs2529155, rs2529168, rs2700292, rs2700296, rs10267234, rs150512506, rs28840812, rs111933649, and rs78748801 (see, e.g., Table 1 which discloses “Mean allele frequencies of the associated SNPs at the DNAH11 locus”). However, the originally filed disclosure does not teach the particular alleles at the SNPs and methods of detecting the particular alleles at the SNPs to identify a subject as having “an increased risk, susceptibility or predisposition to asthma.”
Applicants are required to cancel the new matter in reply to this Office Action.
Maintained Improper Markush Grouping Rejection
7. Claims 1, 5-8, 21, and 22 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 rs2529168, rs2529136, rs2429063, rs2529155, “7:21303293,” rs2700292, rs2700296, “7:21328865,” rs0267234, rs150512506, rs28840812, rs111933649, rs78748801 and SNPs in linkage disequilibrium with any of these SNPs, 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 “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 SNP has a different chemical structure in that it consists of a different nucleotide alteration that occurs at a different location in a locus encoding the DNA11H gene and each SNP is flanked by a unique nucleotide sequence. Thus, the SNPs do not share a single structural similarity. The only structural similarity present is that all of the SNPs involve nucleotides. The fact that the SNPs comprise nucleotides per se does not support a conclusion that they have a common single structural similarity because the structure of comprising a nucleotide alone is not essential to the common activity of being correlated with asthma. For example, the polymorphism of an A or G at rs2529168 has a distinct chemical structure as compared to, for example, a polymorphism of a G or T at rs2429063 since the variant position can only be understood within the context of the surrounding nucleotides, which are structurally dissimilar, as shown below for these polymorphisms and flanking sequences:rs2529168: CTTCATCTGA A/G TTAATAGAAGrs2429063: ATTAATAAACCC A/G GAGAATGTTA
Accordingly, while the different polymorphisms are asserted to have the property of being indicative of asthma, they do not share a single structural similarity essential to this activity. Note that while the SNPs are present in the DNAH11 locus (including upstream, noncoding sequences), this fact does not establish that the SNPs have a common structure because the flanking nucleotides around each SNP are variable and the property of being a nucleotide in the DNAH11 locus per se does not confer susceptibility to asthma since only particular alleles in the DNAH11 locus are correlated with asthma.
The finding that not all SNPs are correlated with asthma is supported by the teachings in the specification which states “Millions of SNP's have been cataloged in the human genome. Some SNPs such as that which causes sickle cell are responsible for disease. Other SNPs are normal variations in the genome” (para [0019]).
Further, the recited SNPs do not belong to a chemical or art-recognized class because there is no expectation from the knowledge in the prior art that all polymorphisms 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 polymorphisms possess the common property of being diagnostic of asthma.
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. Response to Remarks:
The response states:
“all members of claim 1 share a single structural similarity because they belong to the same art-recognized class of genetic alterations, more specifically, SNPs useful in identifying a subject with a predisposition for asthma. This class of equivalent materials, asthma-associated SNP or specific marker" is identified in the specification as filed at page 5, lines 11-14. As the specification as filed includes this group, the equivalence of its members is satisfied absent some convincing evidence of some degree of non-equivalency of these members.”
These arguments have been fully considered but are not persuasive. The recited grouping of SNPs is not a chemical or art-recognized class because there is no expectation from the knowledge in the prior art that all of the recited SNPs 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 polymorphisms possess the common property of being diagnostic of asthma. That is, there is no evidence that the prior art taught that the SNPs belong to a class of SNPs that are all useful for identifying a subject with a predisposition to asthma or evidence from the prior art that all SNPs in the DNAH11 locus are correlated with a predisposition to asthma. It is only the teachings in the specification itself, and particularly Table 1, that set forth the property that each of the SNPs is useful for identifying a subject with a predisposition to asthma.
MPEP 2173 provides the following example which emphasizes that an “art recognized class” is one in which the prior art teaches the equivalence of the members of the Markush grouping:
“In other words, each member could be substituted one for the other, with the expectation that the same intended result would be achieved. For example, in the context of a claim covering a disposable diaper, a limitation “the fastener selected from the group consisting of a pressure sensitive adhesive and complementary release material, a complementary hook and loop structure, a snap, and a buckle” would likely be considered an art recognized class because a review of the prior art would establish that it was well known that each member could be substituted for each other with the expectation that the intended result (repositionable and refastenable) would occur.”
Herein, Applicant does not point to any teachings in the prior art which establishes that it was well known that the recited SNPs could be substituted for each other with the expectation that the intended result.
Modified Claim Rejections - 35 USC § 112(a) - New Matter
8. 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, 5-8, 14, 16 and 21-22 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 new matter rejection.
The specification as originally filed does not provide support for the amendment to the claims presented in the reply of 30 October 2025 to recite “a G allele in rs2529136, an A allele in rs2429063, a G allele in rs2529155, a G allele in rs2529168, an A allele in rs2700292, a T allele in rs2700296, a G allele in rs10267234, an A allele in rs150512506, a G allele in rs28840812, a C allele in rs111933649, and a G allele in rs78748801.”
The originally filed application teaches the particular SNPs recited in the claims but does not disclose the particular alleles of the SNPs.
In the reply of 30 October 2025, Applicant states:
“Submitted SNP(ss) Details: ss1324234380 (submitted August 16, 2014) has been provided in the as Appendix A filed herewith. This reference clearly indicates that rs2529136 has two alleles, A and G, and that the A allele is the major allele, or usual base, with a ~85% frequency in African patients, while the G allele is the minor allele, or the allele with lesser frequency, with a 15% frequency in African patients.
Accordingly, it would be clear to the person of skill in this art area that the G allele is the risk allele. As this process could be repeated for each of the recited SNPs, Applicant respectfully submits that each of the recited risk alleles would be clear to the person skilled in the art.”
However, the originally filed specification did not disclose the particular minor alleles for each of the recited SNPs and did not incorporate by reference the information at dbSNP for each of the recited SNPs. In particular, the specification did not incorporate by reference the specific teachings of the submission of ss1324234380 provided in the Appendix to the response for the elected SNP rs2529136.
While the person skilled in the art may be able to review the various submissions provided at dbSNP for the recited SNPs, this does not establish that the disclosure as originally filed provided basis for the limitations in claims 1, 5-8, 14, 16, 21 and 22 of detecting a G allele in rs2529136, an A allele in rs2429063, a G allele in rs2529155, a G allele in rs2529168, an A allele in rs2700292, a T allele in rs2700296, a G allele in rs10267234, an A allele in rs150512506, a G allele in rs28840812, a C allele in rs111933649, and a G allele in rs78748801 as indicative that an African American subject or other subject (claims 21 and 22) has a predisposition to asthma.
Note that the specification defines an “asthma-associated SNP” as follows (para [0018]; para numbering with respect to the published application):
“Asthma-associated SNP or specific marker” is a SNP or marker which is associated with an increased or decreased risk of developing asthma and found in lesser frequency in normal subjects who do not have this disease..”
The specification (para [0057]) goes on to state:
“Nucleotides comprising asthma-associated single nucleotide polymorphisms (SNPs) as described herein in the Tables, for example at Table 1, may be used for a variety of purposes in accordance with the present invention.”
Table 1 is preceded by the following text:
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Thus, the specification teaches that an allele at the SNPs listed in Table 1 may be associated with an increase or a decreased risk of asthma. The disclosure does not teach that Table 1 intends to indicate that it is the minor (less common) allele of the SNPs that is associated with an increased risk of developing asthma.
Paragraph [0124] refers to the risk allele at rs52529168 but does not identify what constitutes the risk allele: “The effects of homozygosity for the risk allele on ciliary beat frequency and ciliary waveform can be determined by isolating ciliated nasal epithelial cells with all 3 genotype states, and using video microscopy to assess the influence of the rs52529168 SNP allele.”
Additionally, the specification (para [0115]) teaches “Taken together, our results demonstrate that common variants at 7p15.3 in WGS data from AA children with early onset asthma and recurrent exacerbations, associate with the disease, a novel locus which has not been previously reported in larger GWAS of asthma in European ancestry adults.” (Emphasis added). This teaching also does not support a finding that the originally filed disclosure taught that the minor (less common) allele at the SNPs is associated with an increased (and not a decreased) risk of asthma.
If Applicant maintains that the originally filed disclosure provides basis for the amended claims, Applicant should point to specific teachings (e.g., by paragraph number) in the present application to establish basis for each of the recitations set forth in the claims.
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” which 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.”
Modified Claim Rejections - 35 USC § 112(a) - Enablement
9. Claims 1, 5-8, 14, 16, 21 and 22 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 claim(s) contains 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.
The following factors have been considered in formulating this rejection (In re Wands, 858F.2d 731, 8 USPQ2d 1400 (Fed. Cir. 1988): the breadth of the claims, the nature of the invention, the state of the prior art, the relative skill of those in the art, the predictability or unpredictability of the art, the amount of direction or guidance presented, the presence or absence of working examples of the invention and the quantity of experimentation necessary.
The claims are drawn to methods of identifying and/or treating a subject of wherein the methods require detecting a rs2529168 SNP, wherein the presence of an allele at the SNP in the rs2529168 SNP or is indicative that a subject is predisposed to asthma (claims 1, and 3-8) or has asthma (claims 14 and 16) or is in need of treatment for asthma (claims 21 and 22). Claims 1, 5-8, 14 and 16 limit the subject to one of African descent; claims 21 and 22 encompass any subject.
The claims were amended in the reply of 30 October 2025 to recite the detection of the G allele at rs2529168.
However, the disclosure as originally filed did not indicate which allele at rs2529168 is indicative of a predisposition to asthma (claims 1, 5-8) or the occurrence of asthma (claims 14 and 16) or the need to treat a patient for asthma (claims 21 and 22).
Rather, the originally filed specification (para [0018], with respect to the published application) defines an “asthma-associated SNP” as follows:
“Asthma-associated SNP or specific marker” is a SNP or marker which is associated with an increased or decreased risk of developing asthma and found in lesser frequency in normal subjects who do not have this disease..”
The specification (para [0057]) goes on to state:
“Nucleotides comprising asthma-associated single nucleotide polymorphisms (SNPs) as described herein in the Tables, for example at Table 1, may be used for a variety of purposes in accordance with the present invention.”
Table 1 is preceded by the following text:
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Thus, the originally filed specification teaches that an allele at the SNPs listed in Table 1 may be associated with an increase or a decreased risk of asthma. The originally filed disclosure does not teach that the minor allele at SNP rs2529168 is the allele that is associated with an increased risk of developing asthma.
The specification teaches performing a whole genome sequencing analysis to identify a locus in the genome that is correlated with asthma in African American (AA) asthmatics (para [0114]). It is stated that “(o)ur association analysis identified multiple genome wide significant SNPs at a novel locus on chr7p15.3 that has not been previously associated with asthma” (para [0114]).
The specification states:
“The associated variants mapped to an intergenic region upstream of DNAH11 (rs2529168, disc P 4.7×10−8, OR 1.47; rep P 0.018; chr7:21315470 (GRCh38.p12)). As mentioned above, DNAH11 encodes a ciliary dynein protein that is involved in the movement of respiratory cilia. Recessive LOF mutations in DNAH11 result in primary ciliary dyskinesia which is characterized by bronchiectasis and upper respiratory tract infections. Rare variant analysis in DNAH11 identified 17 alleles in the cohort distributed between 12 rare variants all of unknown significance. Burden and SKAT tests were not significant, indicating these rare variants were unlikely to be driving the association and hence, are not explaining the association results captured by the common variants at this locus. Taken together, our results demonstrate that common variants at 7p15.3 in WGS data from AA children with early onset asthma and recurrent exacerbations, associate with the disease, a novel locus which has not been previously reported in larger GWAS of asthma in European ancestry adults.”
Thus, the specification teaches that rs2529168 maps to an intergenic region upstream of the DNAH11 gene and that this SNP, and other SNPs at 7p15.3, were linked with early onset asthma and recurrent exacerbations in African American subjects.
Note that the above teachings as they refer to “common variants” do not support a finding that the originally filed disclosure taught that the minor (less common) allele at the SNPs is associated with an increased (and not a decreased) risk of asthma.
The specification teaches that the biological function of the DNAH11 gene as it relates to asthma is not known (para [0115]). It is postulated that “the associated variants are capturing a regulatory element, eQTL signal or an enhancer that is responsible for the pathogenic asthma risk effects” (para [0115]).
In Table 1, the specification provides mean allele frequencies for one of the alleles at the SNPs in cases versus controls:
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For the elected SNP, the unspecified allele was present at a frequency of 0.15 in replication cases versus 0.14 in replication controls, yet still yielded a p value of 0.013.
The specification does not disclose which allele at rs2529168, or at any of the other SNP locations recited in table 1, are the “risk allele” that is diagnostic of asthma or a predisposition thereto. The specification does not provide sufficient guidance for practicing the claimed methods since the specification does not disclose what constitutes a risk allele at rs2529168 (or at any of the other SNPs recited in Table 1).
It is also not clear from the teachings in the specification that a risk allele at rs2529168 has in fact been identified since the specification appears to teach that genotypes that are homozygous for the major and homozygous for the minor allele were detected in the subjects studied. For example, the specification (para [0122]) states: “(w)e have currently generated multiple homozygous major allele and heterozygous SNP carrier lines, and we have also identified patients who are homozygous for the minor allele.”
The art of identifying SNPs associated with a phenotype, such as asthma, is highly unpredictable, particularly when a functional effect of the SNP is not known and there is minimal difference in the frequency of an allele between subjects having the phenotype and subjects not having the phenotype.
The unpredictability of establishing a correlation between a polymorphism and a phenotype is well accepted in the art. For example, Cohen et al (Shock. 2020 March. 53(3): 256-268; previously cited) teaches that recent studies suggest “that a large portion of SNP studies are not reproducible” (abstract). Cohen (p. 2) further states that:
“With approximately 4–5 million SNPs in the human genome (i.e. gene sequence variations with >1% frequency in the human population (18, 19)), the possibility of spurious SNP-disease associations is a major concern; thus, we suggest that the ultimate clinical utility of assessing particular SNPs will likely depend on validation and quality control (QC) measures. Additionally, the interplay between SNPs and pathology, physiologic responses, and pharmaceuticals all contribute to clinical outcomes.
Illustrating the crucial need for validation in SNP studies, a well-powered replication and validation study of 70 previously published studies of SNPs associated with clinical outcomes after blood or marrow transplantation found only one validated SNP of the 45 SNPs studied.”
An article co-authored by the present inventor (Hakonarson et al, “Current Concepts on the genetics of asthma” Current Opinion in Pediatrics. 2001. 13: 267-277) teaches that, with the exception of a study demonstrating that a polymorphism in the CC16 gene was significantly correlated with risk of developing asthma, other association studies have not provided significant, reproducible results (p. 270, col. 1). It is stated (p. 270, col.1):
Apart from this study, more than 150 genetic linkage and association studies have reported more than 500 atopy and asthma loci throughout the genome. This was done most commonly by associating one of several asthma-associated phenotypes—atopy, IgE levels, and bronchial hyperresponsiveness (BHR)—to microsatellite markers or SNPs within specific TH2-type cytokine or IgE regulating genes [5•,37–39]. However, none of the linkage studies have found loci that meet reasonable criteria for significance [30], and only a few of the association studies reported qualify for possible significance.
In addition, consistency in replication of these studies is often difficult, suggesting either that there may be a wide range of variability in allelic frequencies of these genes between different races and populations [1–4,5•,30] or that the original loci possibly represent false-positive associations or linkages.
The unpredictability in the art as to which allele at a given locus will be the risk allele is supported by the teachings of White et al. (Immunogenetics. 2016. 68(6-7): 391-400). White (p. 6 “Asthma GWAS”) teaches that the minor allele at rs17446324 was a protective allele (correlated with decreased risk for asthma), whereas the minor alleles at rs660498 and rs67731056 were associated with an increased risk of asthma.
Regarding claims 21 and 22, the level of unpredictability in the art is further increased since these claims are directed to methods of treating asthma in any patient, whereas the results provided in the specification are limited to subjects that are African American. There is a high level of variability in the identity of susceptibility loci for asthma in different populations. For example, Almoguera (American J. Respir Crit Care Medicine. Online 09 September 2016. 195(4): 456-463; co-authored by the present inventors) teaches that loci at 6p21.31, 9p21.2, and 10q21.3 were correlated with asthma in European Americans, whereas the PTGES loci was correlated with asthma in African Americans (p. 460, col. 2 and abstract).
Case law has established that '(t)o be enabling, the specification of a patent must teach those skilled in the art how to make and use the full scope of the claimed invention without ‘undue experimentation.'" In re Wright 990 F.2d 1557, 1561. In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970) it was determined that '(t)he scope of the claims must bear a reasonable correlation to the scope of enablement provided by the specification to persons of ordinary skill in the art." The amount of guidance needed to enable the invention is related to the amount of knowledge in the art as well as the predictability in the art. Furthermore, the Court in Genetech Inc. v Novo Nordisk 42 USPQ2d 1001 held that '(I)t is the specification, not the knowledge of one skilled in the art that must supply the novel aspects of the invention in order to constitute adequate enablement".
Moreover, as set forth in Rasmusson v. SmithKline Beecham Co., 75 USPQ2d 1297, 1302 (CAFC 2005), enablement cannot be established unless one skilled in the art "would accept without question" an Applicant's statements regarding an invention, particularly in the absence of evidence regarding the effect of a claimed invention. Specifically:
"As we have explained, we have required a greater measure of proof, and for good reason. If mere plausibility were the test for enablement under section 112, applicants could obtain patent rights to "inventions" consisting of little more than respectable guesses as to the likelihood of their success. When one of the guesses later proved true, the "inventor" would be rewarded the spoils instead of the party who demonstrated that the method actually worked. That scenario is not consistent with the statutory requirement that the inventor enable an invention rather than merely proposing an unproved hypothesis."
Herein, in view of the unpredictability in the art, and the lack of disclosure and guidance provided in the specification and in the prior art, it would require undue experimentation for one of skill in the art to make and use the invention as broadly claimed.Response to remarks regarding the enablement and new matter rejections:
Applicants argue that they are not required to describe in detail subject matter that is already well known to a person of ordinary skill in the art. It is argued that “incorporation of the SNP identifier itself provides sufficient information for a skilled artisan to determine the corresponding alleles without undue experimentation.”
These arguments have been fully considered but are not persuasive. Applicant did not incorporate by reference the subject matter of dbSNP in the originally filed application with respect to the elected SNP or the other SNPs recited in the claims as providing the identity of the allele which is indicative of a predisposition to asthma in African American subjects or any other subjects (claims 21 and 22). Note also that dbSNP does not appear to teach the identity of minor alleles for the SNPs in a representative number of non-human subjects, as encompassed by claims 21 and 22.
The response also states: “the skilled artisan would be able to identify which allele identified on the dbSNP database is the asthma-associated SNP because the definition of "asthma- associated SNP" clearly states that it is "found in lesser frequency in normal subjects who do not have the disease." (See page 5, lines 11-14 of the specification as file.”
However, dbSNP discloses the frequency of the minor and major alleles of a SNP in different ethnic groups in the general population. dbSNP does not specifically disclose the allele of the SNPs "found in lesser frequency in normal subjects who do not have the disease."
Moreover, the teachings at p. 5, lines 11-14 do not specify that it is the less frequent (minor) allele at the SNP that is indicative of increased risk of asthma. Rather, p. 5, lines 11-14 of the specification states:
“’Asthma-associated SNP or specific marker’ is a SNP or marker which is associated with an increased or decreased risk of developing asthma and found in lesser frequency in normal subjects who do not have this disease. Such markers may include but are not limited to nucleic acids, proteins encoded thereby, or other small molecules.”
Thus, these teachings indicate that a minor allele of a SNP may be associated with either an increased risk of asthma or with a decreased risk of asthma. The specification does not teach which minor alleles of the SNPs are associated with an increased risk of asthma and which are associated with a decreased risk of asthma.
Since the specification does not teach the particular allele at the SNP that is correlated with an increased risk of developing asthma, it is maintained that the disclosure as originally filed does not provide support for the amendment to the claims to recite the particular alleles at the SNP, and particularly, with respect to the elected species, for the recitation of detecting a G allele at SNP rs2529168 as indicative of the subject having a predisposition to or as having asthma or treating asthma in a patient having a G allele at rs2529168.
It is also maintained that the specification has not enabled the claimed methods since the disclosure as originally filed does not teach the particular identity of the allele at SNP rs2529168 that is correlated with an increased predisposition to or risk of having asthma and the results presented in Table 1 for the elected rs2529168 SNP show that
the unspecified allele was present at a frequency of 0.15 in replication asthma cases versus 0.14 in replication controls and thereby also does not clarify the identity of the allele that is indicative of an increased risk of predisposition to asthma or increased risk of asthma or need to treat asthma in a patient.
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/CARLA J MYERS/Primary Examiner, Art Unit 1682
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