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 .
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
DETAILED ACTION
Election/Restrictions
Applicant’s election without traverse of Group II (Seq 5, 31, 32, or 33) in the reply filed on 11/5/25 is acknowledged.
Claims 1-13 are pending and under examination.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code; see page 16. 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.
The disclosure is objected to because of the following informalities: Sequences meeting the requirement for a SEQ ID must be identified as such. For example, table 1 on page 14 contains at least four contiguous, enumerated amino acids (such as VYKSPVV) but is not accompanied by a SEQ ID NO. Note that indicating an amino acid is phosphorylated still meets the criteria for an enumerated amino acid.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 2, 4, and 9-12 rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim 2 requires the antigenic peptide of claim 1 has at least two phosphorylated amino acids. The antigenic peptide must comprise an option 1-6, all of which already have at least two phosphorylated amino acids (lowercase “p”). Claim 2 does not provide any further limitation of claim 1.
Claim 4 requires the antigenic peptide to be one of 1-6 in claim 1. Claim 1 already requires the antigenic peptide to be one of 1-6. While claim 1 states that the peptide “contains” and claim 4 states that the peptide “is”, the broadest, reasonable interpretation of both of these phrases is “comprises”. The instant specification does not contain any special definition of “contains” or “is”. Based on the specification as a whole, interpreting “is” as “consists of” would be narrowing of the interpretation without proper justification.
Claim 9 recites an intended use. There is no evidence in the specification or art of record that the intention of using an antigenic peptide + carrier for this particular purpose alters the composition itself in any particular way. As such, a claim wholly indicating the intended use of a composition does not further limit that composition.
Claim 10 recites an intended use. There is no evidence in the specification or art of record that the intention of using an antigenic peptide + carrier for this particular purpose alters the composition itself in any particular way. As such, a claim wholly indicating the intended use of a composition does not further limit that composition.
Claim 11 recites an intended use in the preamble (“for treating tauopathy”), which does not alter the structure of the composition and so does not further limit the composition. The claim also refers to the composition as a “vaccine” comprising the composition of claim 1. A preamble recitation does not alter the scope of a claim where the body of the claim defines a structurally complete invention (MPEP §2111.02(II)). The specification does not set forth any special definition of a “vaccine” and the term appears directed to the intention (treatment/prevention) rather than the composition itself. Based on the evidence, claim 11 does not add any further limitations.
Claim 12 recites an intended use. There is no evidence in the specification or art of record that the intention of using an antigenic peptide + carrier for this particular purpose alters the composition itself in any particular way. As such, a claim wholly indicating the intended use of a composition does not further limit that composition.
Therefore, claims 2, 4, and 9-12 fail to further limit the claim.
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 1-5 and 7-12 are rejected under 35 U.S.C. 101 because:
Step 1: It must first be determined if the claim is to a statutory category and, if so, proceed to step 2A prong 1. The claims are an immunogenic composition and fall within the statutory category of a composition.
Step 2A, prong 1: Prong 1 requires the Examiner to evaluate whether the claim recites a judicial exception and, if so, proceed to prong 2. In this case, claim 1 requires two elements: a human tau protein fragment and a carrier. These two elements do not need to interact in any way but rather must be found in the same “composition”.
The human tau protein fragment is a naturally occurring sequence. The instant specification discloses the sequences of human tau (e.g., p.6) as well as that these fragments are pathological tau (p.7). As the tau is disclosed as a pathologic agent in human disease, this supports the conclusion that these are naturally occurring. Subramanian (instantly cited) also teaches this phosphorylated sequence is from the N-terminus of tau.
The carrier is “not particularly limited” (specification p. 8). These include a number of other naturally occurring proteins including EGF and FGF. Tau naturally occurs in blood (US 20180312608 claim 21; form 892) as does EGF (US20150141332 claim 1; form 892), supporting the conclusion that these two naturally occurring proteins also naturally occur in combination.
Thus, the claims recite a natural product, which is a judicial exception.
Step 2A, prong 2: Prong 2 requires the Examiner to evaluate whether the claim recites additional elements that integrate the exception into a practical application of that exception and, if not, proceed to step 2B. In order to integrate the recited judicial exception into a practical application, the claim will apply, rely on, or use the judicial exception that imposes a meaningful limit such that the claim is more than a drafting effort to monopolize the judicial exception. Examiners evaluate integration by identifying additional elements in the claim beyond the judicial exception and evaluating those elements individually and in combination to determine whether they integrate the exception in to a practical application. Examples that have been found by the Courts in which the exception was not integrated into a practical application include:
Mere instructions to implement an abstract idea on a computer
Adding generic instructions that the judicial exception should be used ("apply it")
Adding insignificant extrasolution activity to the exception ("mere data gathering")
Generally linking the use of the exception to a particular technological environment or field of use
In this case, the preamble of “immunogenic composition” does not structurally alter any element of the JE. There is nothing in the claim that would distinguish a composition comprising the naturally occurring tau and carrier from an “immunogenic” composition comprising the same elements.
With respect to claim 2, the phosphorylation is also naturally occurring as discussed above.
With respect to claim 3, the instant specification suggests that these fragments are naturally occurring as discussed above. Further, even if the natural fragments are longer, merely isolating a naturally occurring sequence from other natural amino acids is not sufficient to add significantly more; see the decision in Myriad 133 S. Ct. at 2116-2118.
With respect to claim 4, the peptides in claim 1 are naturally occurring as discussed above.
With respect to claim 5, the claim refers to a property of the antigenic peptide, i.e., what the peptide is capable of eliciting antibodies against. This does not alter the structure of the naturally occurring proteins and is considered an inherent property.
With respect to claim 7, as discussed above, the “carrier protein” is not limited by the specification. The claimed tau fragments conjugated to their native flanking residues would meet the limitations of the claimed fragment and a carrier. Claim 7 appears to include the intact, naturally occurring tau protein and no more.
With respect to claim 8, the specification does not provide any special definition of an adjuvant. Squalene and cytokines are known adjuvants (US 20180186885 claim 133; form 892) and occur in human blood (US 20160024457 paragraph 3; form 892)(US20180369162 paragraph 45; form 892).
With respect to claims 9-10, these claims add an intended use which does not alter the structure of the naturally occurring elements nor inherently add any non-naturally occurring elements.
With respect to claim 11, referring to the immunogenic composition as a vaccine does not structurally alter the naturally occurring elements nor inherently add any non-naturally occurring elements.
With respect to claim 12, this claim adds an intended use which does not alter the structure of the naturally occurring elements nor inherently add any non-naturally occurring elements.
In summary, none of the rejected claims add any elements beyond a combination of naturally occurring elements and so there are no additional elements to integrate the exception.
Step 2B: Where a claim does not integrate the exception, a claim may nevertheless be patent eligible, for example where additional elements are “significantly more” than the exception such that the additional elements were unconventional in combination. Considerations include whether or not the claim adds a specific limitation or combination of limitations that are not well-understood, routine, conventional activity in the field, which is indicative that an inventive concept may be present; or simply appends well-understood, routine, conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception, which is indicative that an inventive concept may not be present. In this case, as noted above, none of the rejected claims add any elements beyond the judicial exception itself and so there are no additional elements which are significantly more.
Therefore, claims 1-5 and 7-12 are not patent eligible. Claim 6 is not included because, while KLH is also naturally occurring, the two proteins do not naturally occur in combination. Claim 13 is not rejected because this is a method which practically applies the natural product.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1-5 and 7-13 is/are rejected under 35 U.S.C. 103 as being unpatentable over Subramanian (form 892) in view of Sigurdsson (US20080050383; form 892)
Regarding claim 1, Subramanian teaches the peptide TPTEDGSEEPGSETSDAKpSpTPpT, with the underlined residues meeting the criteria for the first six residues of instant option 2 including the phosphorylation of specific residues (abstract; p.586 C1). The instant specification does not define “carrier” but rather states that the term is not particularly limited (p.8). The non-underlined amino acids therefore meet the limitations of a carrier. Subramanian also teaches the phosphor-peptide was mixed in saline (p.586 C2), which also meets the limitations of a carrier. Subramanian teaches that the important residues of this peptide are the phosphorylated S68, T69, and T71 because these are “pathologically relevant” (abstract). Subramanian teaches this peptide elicits antibodies (p.586 C2) and the produced peptides bind phospho-tau (p.586 C2) meeting the limitation of both immunogenic (elicits antibodies) and antigenic (bound by antibodies; is an antigen). Subramanian does not teach including the next two native amino acids of “AE”.
Sigurdsson is also concerned with using immunogenic tau epitopes (abstract; claim 31) including phosphorylated tau peptides (claim 33). Sigurdsson teaches one such immunogenic tau epitope is SEQ ID NO: 6 (claim 31), aligned with the peptide of Subramanian below:
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Sigurdsson also teaches including these peptides with carriers (claim 35), that these peptides induce an immune response (immunogenic; claim 35), are bound by antibodies (claim 36; antigenic), and is used to clear pathological tau (claims 12, 16, 17, 21).
One of ordinary skill in the art would have found it obvious to combine the references above and arrive at a phosphorylated antigenic peptide comprising AKSTPTAE and further comprising a carrier. Subramanian teaches the peptide above, which is residues 50-71 of tau and includes the specifically claimed phosphorylation sites. Sigurdsson teaches the peptide above, which is residues 60-90 of tau and that serine and tyrosine residues are phosphorylated (paragraph 33). Further, both teach that their respective peptides are immunogenic, antigenic, and relevant to tau pathology. This would have led to the reasonable expectation that fragments within this span (50-90) would have similar properties. One would have been motivated to preserve the phosphorylation on residues 68, 69, and 71 because Subramanian teaches phosphorylation of these specific residues are important while Sigurdsson teaches the importance of phosphorylated serine and threonine in general when generating phospho-specific antibodies. Thus, it would have taught the person of ordinary skill in the art that the peptide of pSpTPpT (four amino acids) is the region to keep while the peptide may be extended in both the N- and C-terminal direction. It would have been obvious that the peptide of Subramanian could have included two additional amino acids (AE) up to the whole of the combination (50-90) while still having a reasonable expectation of preserving the relevant properties (capable of eliciting production of an antibody against a phosphorylated tau protein) because Sigurdsson teaches these additional amino acids do not negatively affect those properties.
Regarding claim 2, Subramanian teaches that residues 68, 69, and 71 being phosphorylated is important as above, meeting the limitation of “at least two”.
Regarding claim 3, there is no special definition of a carrier protein. The additional amino acids flanking the antigenic peptide are fairly considered a carrier. The phrase “antigenic carrier” is interpreted as describing a property whereby the residues of 66-73 in the above peptide are the “antigenic peptide” (eight amino acids) and the additional residues are not the “antigenic” peptide but rather amino acids in addition to the antigenic peptide, e.g., carrier residues. An antigenic peptide is one capable of being bound by an antibody. There is nothing in the instant specification nor in the art of record that suggests any particular property of an amino acid sequence that makes the sequence “antigenic”. As used in the claim in light of the specification, this appears to be an administrative label to differentiate between the antigenic and the carrier proteins but does not require any specific limitation on calling any particular portion of the peptide “antigenic”. Moreover, the Office is not equipped to make and test the prior art peptides to determine the exact residues which serve as the antigenic binding region. As the prior art combination appears to meet all of the structural limitations, the determination of calling one portion the antigenic peptide (such as the eight residues of the claim and found in the prior art combination) and the other amino acids the carrier (such as any additional amino acids), there is a prima facie case that the prior art combination meets these limitations.
Regarding claim 4, option 2 of claim 1 is discussed above. Further, as set forth in the §112(d) rejection, the broadest reasonable interpretation of the term “is” is “comprising”. This is further supported in that the antigenic peptide may be conjugated to additional amino acids (see claim 7). Alternately, this could also be describing a property whereby the residues of 66-73 in the above peptide are the “antigenic peptide” and the additional residues are not the “antigenic” peptide but rather amino acids in addition to the antigenic peptide, e.g., carrier residues.
Regarding claim 5, this claim is directed to a property of the peptide, i.e., what it is capable of. As all of the structural elements of the claim would have been obvious, these properties are considered inherent. Moreover, as above, both Subramanian and Sigurdsson teach their individual peptides elicit antibodies against a phosphorylated tau protein and so this property would have been reasonably expected from the combination.
Regarding claim 7, as above, there is no special definition of a carrier protein. The additional amino acids flanking the antigenic peptide are fairly considered a carrier. As these amino acids are connected via covalent peptide bonds, this also meets the limitations of a conjugate of the antigenic protein and the carrier protein; note that “conjugate” similarly does not have a specific definition in the specification and the broadest reasonable interpretation would be the two proteins connected in some manner rather than existing as separate elements in the composition.
Regarding claim 8, Subramanian teaches including Freund’s complete adjuvant (p.586 C2). Sigurdsson also teaches including an adjuvant (paragraphs 53, 58, 63, 64; claims 35 and 42). As both references teach including an adjuvant in the immunogenic composition, it would have been obvious to include an adjuvant in the combination for the same reasons.
Regarding claims 9 and 10, these are intended use claims. The intention to use the composition “for treatment of tauopathy” or “for treatment of Alzheimer’s disease” does not structurally alter the composition. There is no evidence that the combination above could not be used for such and so meets the limitations of these claims. Further, Sigurdsson teaches using the immunogenic peptides to treat Alzheimer’s disease (claims 1, 10, 11) and this use is also suggested by Subramanian (abstract; sections 2.4-2.6; results demonstrating the elicited antibodies are effective in a model of tauopathy).
Regarding claims 11-12, the limitations of “for treating tauopathy” and “for treating Alzheimer’s disease” are addressed above. Also as above, referring to the immunogenic composition as a “vaccine” does not imply any specific structural change. A composition which meets all of the limitations of instant claim 1 also appears to be a “vaccine” within the meaning of the term, which is directed to the composition’s use rather than structure. Further, Sigurdsson teaches the composition as a vaccine (paragraph 13, 15; example 7) while Subramanian identifies the peptide “for AD/tauopathy vaccine development” (p.589 C1). Given these teachings along with the above teachings such as eliciting phospho-specific antibodies which reduce tauopathy etiology, one of ordinary skill would have found it obvious to formulate the “immunogenic” composition as a vaccine for treating AD.
Regarding claim 13, given the teachings regarding using the peptide as a vaccine along with the above teachings such as eliciting phospho-specific antibodies which reduce tauopathy etiology, one of ordinary skill would have found it obvious to administer the composition of claim 1 to treat tauopathy with a reasonable expectation of success. Both Subramanian and Sigurdsson administered their peptides to mice and saw benefits in tauopathy pathology, providing a reasonable suggestion to administer to mice (an animal). Sigurdsson teaches administration to treat humans (paragraph 117).
Therefore, claims 1-5 and 7-13 would have been obvious.
Claim(s) 3 and 6 is/are rejected under 35 U.S.C. 103 as being unpatentable over Subramanian in view of Sigurdsson as applied to claims 1-5 and 7-13 above, and further in view of Smith (US20110177109; form 892).
The teachings of Subramanian and Sigurdsson are discussed above and incorporated herein.
Regarding claim 3, the combination of Subramanian and Sigurdsson would have made obvious a peptide comprising the claimed phosphorylated tau fragment as above. Further, there is no particular quality of the amino acids themselves which make them “antigenic” or a “carrier” and so the limitations would have been met as above. However, it is further set forth that it would have been obvious to truncate the combined peptide of Subramanian/Sigurdsson (41 amino acids) to 10 or fewer amino acids.
It would have been obvious to arrive at a peptide comprising the instant sequence as described above. This combination would be 24 amino acids (when adding just two amino acids; residues 50-73) to 41 amino acids (when combining the whole of the two peptides; residues 50-90). However, Subramanian makes clear that the phosphorylated residues 68, 69, and 71 are the important residues when it comes to eliciting the phospho-specific antibodies relevant to tauopathy pathology (see above). One of ordinary skill in the art is therefore informed that four residues—pSpTPpT—should be preserved.
Smith is also concerned with using phosphorylated tau fragments to elicit antibodies (immunogenic/antigenic); see for example abstract and claim 1. Smith further teaches “antigenic sites typically comprise 5 to 10 amino acids” (paragraph 81).
One of ordinary skill in the art would therefore have found it obvious to minimize the 24-41 amino acid peptide of Subramanian/Sigurdsson to one that is 5-10 amino acids because Smith teaches this is a common antigenic length and both Subramanian and Sigurdsson taught their peptides as antigenic. One would have been motivated to preserve the core four amino acids that were taught by Subramanian as important to the immunogenic properties of the peptide. This creates a finite number of potential fragments that would have predictably also produced antibodies because the art teaches various permutations of phospho-tau that each predictably possess this property.
Regarding claim 6, both Subramanian and Sigurdsson teach including carriers as above. Sigurdsson specifically teaches including non-tau proteins as carriers (paragraph 67) but does not explicitly suggest KLH.
Smith—also concerned with formulating phospho-tau fragments to elicit an immunogenic response—teaches that KLH is a preferred carrier (paragraph 144). This would have made including the KLH as a carrier obvious.
Therefore, claims 1-13 would have been obvious.
Conclusion
Claim 3 states the antigenic peptide has a length of 10 amino acids “or less”. While the phrase “or less” would ordinarily include, e.g., zero or one amino acid, claim 3 depends from claim 1 where the antigenic peptide requires at least 7 amino acids (option 6). Thus, the broadest, reasonable interpretation is that the antigenic peptide is 7-10 amino acids.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ADAM M WEIDNER whose telephone number is (571)272-3045. The examiner can normally be reached M-T 9-18; W-R 9-15.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey Stucker can be reached at 571-272-0911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Adam Weidner/ Primary Examiner, Art Unit 1675
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