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 the following species in the reply filed on 3/18/26 is acknowledged:
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The following is necessitated by applicant’s amendment on 3/18/26 of claims 14 and 15 to method claims, and the addition of new claim 16, also a method claim.
REQUIREMENT FOR UNITY OF INVENTION
As provided in 37 CFR 1.475(a), a national stage application shall relate to one invention only or to a group of inventions so linked as to form a single general inventive concept (“requirement of unity of invention”). Where a group of inventions is claimed in a national stage application, the requirement of unity of invention shall be fulfilled only when there is a technical relationship among those inventions involving one or more of the same or corresponding special technical features. The expression “special technical features” shall mean those technical features that define a contribution which each of the claimed inventions, considered as a whole, makes over the prior art.
The determination whether a group of inventions is so linked as to form a single general inventive concept shall be made without regard to whether the inventions are claimed in separate claims or as alternatives within a single claim. See 37 CFR 1.475(e).
When Claims Are Directed to Multiple Categories of Inventions:
As provided in 37 CFR 1.475 (b), a national stage application containing claims to different categories of invention will be considered to have unity of invention if the claims are drawn only to one of the following combinations of categories:
(1) A product and a process specially adapted for the manufacture of said product; or
(2) A product and a process of use of said product; or
(3) A product, a process specially adapted for the manufacture of the said product, and a use of the said product; or
(4) A process and an apparatus or means specifically designed for carrying out the said process; or
(5) A product, a process specially adapted for the manufacture of the said product, and an apparatus or means specifically designed for carrying out the said process.
Otherwise, unity of invention might not be present. See 37 CFR 1.475 (c).
Restriction is required under 35 U.S.C. 121 and 372.
ELECTION OF INVENTION
This application contains the following inventions or groups of inventions which are not so linked as to form a single general inventive concept under PCT Rule 13.1.
In accordance with 37 CFR 1.499, applicant is required, in reply to this action, to elect a single invention to which the claims must be restricted.
The following regards claims of the 3/18/26 claim set:
Group I, claim(s) 1-12, drawn to a compound comprising a biopolymer scaffold and at least two FVIII peptides as set forth therein, and a pharmaceutical composition comprising same and at least one pharmaceutically acceptable excipient.
Group II, claim(s) 14-16, drawn to a method of treating hemophilia A comprising administering to an individual in need thereof a pharmaceutical composition of claim 10, and a FVIII replacement.
The groups of inventions listed above do not relate to a single general inventive concept under PCT Rule 13.1 because, under PCT Rule 13.2, they lack the same or corresponding special technical features for the following reasons:
The inventions lack unity of invention because even though the inventions require the technical feature of compound that comprises a biopolymer scaffold and at least two peptides derived from factor VIII "with a sequence length of 6-13 amino acids", "wherein each of the peptides independently comprises a 6-amino acid fragment of the amino acid sequence of factor VIII" and "wherein at most three amino acids are substituted by any other amino acid", this technical feature is not a special technical feature as it does not make a contribution over the prior art in view of Lei and Scott, Blood, 15 June 2005, Vol. 105, No. 12, pp 4865-4870 ("LS"). LS constructed, expressed, evaluated and teaches fVIII amino acids S2173-Y2332 (C2 domain) and S373-R740 (A2 domain) combined with an IgG heavy chain backbone, the latter within the genus of the claim 1 claimed biopolymer scaffold. See Abstract, Introduction as well as Materials and Methods.
During a telephone conversation with Attorney Berzutskaya on 8/3/26 a provisional election was made without traverse to prosecute the invention of Group II, claims 14-16. Affirmation of this election must be made by applicant in replying to this Office action.
Claims 1-12 are withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected invention, there being no allowable generic or linking claim.
INVENTORSHIP
Applicant is reminded that upon the cancelation of claims to a non-elected invention, the inventorship must be corrected in compliance with 37 CFR 1.48(a) if one or more of the currently named inventors is no longer an inventor of at least one claim remaining in the application. A request to correct inventorship under 37 CFR 1.48(a) must be accompanied by an application data sheet in accordance with 37 CFR 1.76 that identifies each inventor by his or her legal name and by the processing fee required under 37 CFR 1.17(i).
Claim Status
Claims 1-12 and 14-16 are pending.
Claims 1-12 are withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected invention, there being no allowable generic or linking claim.
Claims 14-16 are pending and under examination.
Claims 14-16 are rejected.
Priority
The instant application, filed 03/20/2023 is a National Stage entry of PCT/EP2021/076182 , International Filing Date: 09/23/2021
claims foreign priority to 20197701.4, filed 09/23/2020.
Information Disclosure Statement
The Examiner has considered the reference(s) provided in the 5/23/23 and 7/28/26 Information Disclosure Statements, and provides a signed and dated copy of each herewith.
Specification
The disclosure is objected to because of the following informalities: on page 66, last paragraph, it appears that “over” is misspelled as “oder” before “SADC-TF”.
Appropriate correction is required.
Claim Interpretation
The claim limitations are given their broadest reasonable interpretation (BRI) consistent with the specification, MPEP 2111, and under the BRI, words of the claim must be given their plain meaning, unless such meaning is inconsistent with the specification, MPEP 2111.01.
The transitional term “comprising” is inclusive or open-ended and does not exclude additional, unrecited elements. See MPEP 2111.03.
Claim 14, the sole independent claim under examination, is interpreted as directed to
A method of treating hemophilia A in an individual in need thereof, the method comprising:
administering to the individual a pharmaceutical composition comprising a compound comprising a biopolymer scaffold and at least two peptides derived from factor VIII with a sequence length of 6-13 amino acids; wherein each of the peptides independently comprises a 6-amino-acid fragment of the amino acid sequence of factor VIII; and wherein at most three amino acids are independently substituted by any other amino acid; and at least one pharmaceutically acceptable excipient; and
administering to the individual a factor VIII replacement product.
Because the transition regarding the compound is “comprising”, a larger polypeptide can include the at least two peptides. “Derived from” is not defined and is interpreted broadly to mean “to come from”, “to develop from” or “to be obtained from”. A change in sequence or structure from what the two peptides are “derived from” is not required but is permitted under this interpretation.
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 14-16 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.
First, as to claim 14 and the limitations imparted by administering the pharmaceutical composition of claim 10, which comprises the compound of claim 1, it is unclear
whether “each of the peptide independently” means that each of the at least two peptides comprises a different 6-amino-acid fragment of the amino acid sequence of factor VIII;
whether the 6-amino-acid fragment is specifically of the amino acid sequence of factor VIII (this can be made clear by eliminating the comma after “fragment”);
given that “comprising” allows for any additional amino acids (as well as other components), what the “wherein at most three amino acids are independently substituted by any other amino acid” refers to, and if to the 6-amino-acid fragment of the amino acid sequence of factor VIII, are at most three substitutions allowed for EACH of the 6-amino-acid fragments of the amino acid sequence of factor VIII, or does this limit of three substitutions apply to the combination of at least two peptides’ 6-amino-acid fragment of the amino acid sequence of factor VIII, or does this limit on substitutions apply to some collective aspect of the peptides as a whole (or, though unlikely, also of the biopolymer scaffold when a polypeptide)? This is not clear.
Claims 15 and 16 also are rejected on the above bases as depending from claim 14.
Second, claim 16 is rejected because it includes a functional limitation – “wherein said administering of the composition inhibits neutralization or inhibition of the factor VIII replacement product in the individual”, but nowhere is the structure for meeting this function set forth. Given the breadth of the claim 14 administered pharmaceutical composition of claim 14 – please note “derived from” interpretation, and that no sequence characteristics related to this function are provided (any number of sequences of the large genus can be based on internally disposed regions of FVIII so not reasonably eliciting any function as claimed), the boundaries of what is claimed are not clear and precise. To conclude, it is unclear what structure in the broad genus of diverse structures provides for the claimed function. Please see MPEP 2173.05(g).
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 16 is 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.
The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed by him. The courts have stated:
“To fulfill the written description requirement, a patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that “the inventor invented the claimed invention.” Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997); In re Gostelli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) (“[T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed.”). Thus, an applicant complies with the written description requirement “by describing the invention, with all its claimed limitations, not that which makes it obvious,” and by using “such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention.” Lockwood, 107 F.3d at 1572, 41 USPQ2d at 1966.” Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the Application. These include “level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention. Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the applicant was in possession of the claimed species is sufficient.” MPEP § 2163. While all of the factors have been considered, a sufficient amount for a prima facie case are discussed below.
First, regarding the elected species, there is no evidence that upon administering the elected species when treating hemophilia A in an individual in need of such treatment that the elected species, when in a pharmaceutical composition comprising at least one pharmaceutically acceptable excipient (such as water), in fact would meet claim 16’s requirement/limitation “inhibits neutralization or inhibition of the factor VIII replacement product in the individual.”
There are two distinct bases for this:
Uncertain and unproven effectiveness given conflicting roles for transferrin in fusion molecules, this additionally supported by applicant’s own concerns with transferrin.
Deng et al., Diabetes, Metabolic Syndrome and Obesity 2024:17 343–362, copy provided, teaches the following (underline emphasis added):
In addition to combining functional proteins with Fc fragments and albumin, transferrin is also used as a bio-carrier for drug delivery, becoming a new fusion form. Transferrin enters the cell in a cytosolic form by binding to Transferrin receptor-1 (TFR1), and subsequently undergoes dissociation in the acidic environment of the endosome. It is then released extracellularly, thereby preventing the degradation of TF and TFR in the lysosome. This process facilitates recycling of transferrin upon release, effectively reusing Transferrin,53 thus improving TF half-life and efficacy. Apart from its application in the treatment of diabetes mellitus through the proinsulin-transferrin fusion protein (ProINS-TF), which will be mentioned later, transferrin can also be used to deliver proteins, drugs or DNA to target cells through diverse binding modalities, including biomolecules and nanoparticle platforms.54–57 The binding of transferrin to nanoparticle-coated insulin has demonstrated resistance to enzymatic hydrolysis and the ability to extend insulin efficacy for up to 10 hours.4
In contrast to this teaching of pathway routing for transferrin, in the review of a text by Berger et al., (2015) Fusion protein technologies for biopharmaceuticals: Applications and challenges, mAbs, 7:3, 456-460, copy of article provided, the following is stated (underline emphasis added):
A new concept for shortening the half-life of autoantibodies is outlined by Dennis Keefe, Michael Heartlein and Serene Josiah. Autoantibodies that block acetylcholine receptors can cause Myasthenia gravis, a severe autoimmune disease. SHG2210 is a fusion protein of the nicotinic acetylcholine receptor a and
human transferrin. Antibodies binding to the fusion protein are guided to the lysosome for proteolytic destruction via transferrin receptor-mediated uptake.
These two resources teach different modes of transferrin entry into a cell and utilization as a fusion protein component. There is no reasonable basis to know whether binding the peptides per the species elected to transferrin operates via one or the other stated pathway, nor whether whichever results would in fact achieve the function claimed in claim 16.
This point is further supported by concerns in the instant specification itself, where it is stated, that haptoglobin scaffold based SADCs are preferred over others, listing SADC-TF last (after “oder” which appears to contain a typographical error and is more logically “over”), referencing potential “their potential role in complement-dependent vascular and renal damage due to the in vivo risk of immunocomplex formation,” page 66, this concern and risk further elucidated on page 68:
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Additionally, the examiner also notes that much if not all evaluation of peptides regarding FVIII was with cyclic peptides, whereas what is claimed appears to provide only linear peptides, and the differences in function are well known in the art.
Overall, lacking evidence of effectiveness relevant to what is claimed (Example 12 appears prophetic, which is allowed, but does not provide evidence as it appears), and given the above, there is a lack of possession of the elected species meeting the functional limitations of claim 16.
The second basis is much simpler: there is no timing set forth between the claim 16 functional limitation and any administering per claim 14 of the FVIII replacement product.
Given normal breakdown of proteins, administering the elected species weeks or months apart from administering the FVIII replacement product would not reasonably meet the claim 16 functional requirement.
Accordingly, based on the above, it is deemed that the specification fails to provide adequate written description for the elected species when administered as claimed regarding the claim 16 functional limitations and does not reasonably convey to one skilled in the relevant art that the inventor(s), at the time the application was filed, had possession of the claimed invention for the elected species.
The following rejection under this section expands the scope of rejection beyond the elected species, for the sake of compact prosecution
Claim 16 expanded beyond the elected species allows for administration of any of a large and diverse genus of compounds, so long as the functional limitation is met. There is tremendous diversity of the genus of administered compounds, and no structure specific to providing for the function claimed in claim 16.
To provide evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include: a) the scope of the invention; b) actual reduction to practice; c) disclosure of drawings or structural chemical formulas; d) relevant identifying characteristics including complete structure, partial structure, physical and/or chemical properties, and structure/function correlation; e) method of making the claimed compounds; f) level of skill and knowledge in the art; and g) predictability in the art.
the scope of the invention – administering any of a very broad and diverse genus of compounds to achieve a functional requirement of claim 16
actual reduction to practice – none in vivo
disclosure of drawings or structural chemical formulas – multiple diverse short amino acid sequences listed in Table 1, however none evaluated with a range of biopolymer scaffolds for what is claimed.
relevant identifying characteristics including complete structure, partial structure, physical and/or chemical properties, and structure/function correlation – given lack of clarity as to what can be modified or lengthened, and how attached to any biopolymer scaffold, identifying characteristics are insufficient to lead one of ordinary skill in the art to understand what is required to achieve the claimed function of claim 16 for species within the genus of possible structures.
method of making the claimed compounds – known in the art
level of skill and knowledge in the art – generally high
predictability in the art – not high given the possibility that small changes will affect binding.
The skilled artisan cannot envision the detailed chemical structure alternatives (i.e., amino acid sequences) of the encompassed peptides which have the respective required activity/function without further testing, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of identification. Adequate written description requires more than a mere statement that it is part of the invention. The compound itself is required; in this case at least a sufficient number of species that are representative of the diversity of each respective genus, and/or a disclosure of what is critical as far as sequence(s) and what does not work to achieve a particular claimed activity/function. Here, given the breadth of possible modifications per “derived from”, and the lack of specific structures/amino acid sequences that are known or shown to bind to relevant paratopes, the skilled artisan is left to determine what range of variations can still provide some level of relevant biological activity. This is leaving completion of the invention to someone else. See also Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016 (Fed. Cir. 1991). One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481 at 1483 (BPAI 1993). In Fiddes, claims directed to mammalian FGF's were found to be unpatentable due to lack of written description for that broad class. The specification provided only the bovine sequence.
Accordingly, based on the above, it is deemed that the specification fails to provide adequate written description for claim 16 functional limitations and does not reasonably convey to one skilled in the relevant art that the inventor(s), at the time the application was filed, had possession of the claimed invention. Therefore, the full breadth of claim 16 does not meet the written description provision of 35 U.S.C. §112, first paragraph.
The following rejections expand the scope of rejections beyond the elected species, for the sake of compact prosecution.
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 (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.
(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.
Claim(s) 14-16 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by ALPHANATE® Prescribing Information Pamphlet, 13 pages 2022 (“Alfa”), copy provided, as evidenced by ALPHANATE® web page “What is ALPHANATE?”, 3 pages, 2025, downloaded 8/4/26 (“Wia”), copy provided.
Claim 14 is set forth and interpreted above.
Alfa teaches that administering a FVIII (~factor VIII)/von Willebrand factor (vwf) complex to treat hemophilia A, pages 1-2, including administering at 12 hour intervals for minor, moderate and major type of bleeding, see Table 1 on page 2.
Considering the claim interpretation that the a larger polypeptide can include the at least two peptides, and that FVIII comprises such at least two peptides as claimed, and that vwf is a biopolymer, the administered FVIII/von Willebrand factor (vwf) complex meets all structural/sequence limitations of what is administered as the compound, and because a diluent of sterile water for injection is used to reconstitute the concentrate before administering, see page 4, the administered solution meets the requirements of the pharmaceutical composition.
Evidentiary reference wia clearly evidences, to any extent not already made uncontravertable in alfa, that the vwf is complexed with the FVIII component so serves as a scaffold, see page 2, reproduced in part here:
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Please note that because the ALPHANATE® FVIII (factor VIII)/von Willebrand factor (vwf) complex is a form of a factor VIII replacement product, administering this meets both administering steps of claim 14. Alternatively, each administering separately meets one of the two administerings of claim 14, so that two or more sequential administerings effectively meets both administerings of claim 14.
Accordingly, alfa anticipates claim 14.
Because alfa Table 1 on page 2 clearly teaches twice daily frequency of doses with durations from 2-7 days, on average, for moderate bleeding type, and for at least 3-5 days “Until healing has been achieved for up to 10 days” for major types of bleeding (excluding longer periods for cranial hemorrhage), and because such administering encompasses both types of administering of claim 14 (the ALPHANATE® FVIII/von Willebrand factor (vwf) complex meeting both types of administering), alfa anticipates claim 15.
Additionally, because a first administering of ALPHANATE® FVIII/von Willebrand factor (vwf) complex would inhibit inhibition of a later administering of the FVIII of the ALPHANATE® FVIII/von Willebrand factor (vwf) complex (this later administering identified as administering factor VIII replacement product) – this based on reducing the titer of autoantibodies against FVIII in the individual, alfa anticipates claim 16.
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) 14 and 16 are rejected under 35 U.S.C. 103 as being unpatentable over US 20100323966, D. Wraith, published 12/23/2010 (Wraith), in view of Lei and Scott, BLOOD, 15 JUNE 2005, VOLUME 105, NUMBER 12, pp 4865-4870 (“LS”).
Claim 14 is set forth and interpreted above.
Wraith abundantly teaches FVIII peptides and their use in tolerizing hemophiliacs, Title, Abstract, which includes the objective “for the prevention or suppression of inhibitor antibody formation in haemophilia A and/or acquired haemophilia, and elsewhere in the specification.
Paras 58-63 teach what Wraith terms apitopes, para 60 stating, “The peptides of the present invention are apitopes (Antigen Processing-Indepent epiTOPES) in that they are capable of binding to an MHC class II molecule and stimulating a response from factor VIII specific T cells without further antigen processing. Such apitopes can be predicted to cause tolerance to FVIII, following the rule-based method described in WO 02/16410.”
Para 64 states that a first aspect of the invention “relates to a peptide comprising one of the following core residue sequences: Table 2 LYISQFIIM FIIMYSLDG IARYIRLHP LIIFKNQAS LTRYYSSFV MVTFRNQAS LRIHPQSWV.
Para 67 states, “The peptide may comprise one of the core residue sequences, together with additional flanking sequences at the N and/or C terminal end, provided that the resulting peptide is capable of binding to an MHC class II molecule without further antigen processing.”
Thus, Wraith teaches these short peptides can have additional flanking sequences, however not to the point of requiring further antigen processing. In that paras 62 and 63 teach peptides that bind to MHC class I molecules are typically 7 to 13, more usually 8 to 10 amino acids in length, and peptides which bind to MHC class II molecules are typically between 8 and 20 amino acids in length, more usually between 10 and 17 amino acids in length, and can be longer (for example up to 40 amino acids), and given the objective to avoid further antigen processing, see above, one of ordinary skill in the art would reasonably develop peptides that have no or few additional amino acids to the N- and/or C-terminus of any of the Table 2 peptides, this resulting in at least some peptides that fall within the sequence length of 6-13 amino acids (Assuming on one hand that the interpretation for this is that the peptide that comprises the FVIII 6-amino-acid fragment is so limited, ignoring the effect of the open transition comprising), or may be longer and also within the scope of what is claimed (this based on the alternative interpretation, namely, given the ambiguity of what is claimed, assuming that each of the peptides can be of any length so long as they comprise a length of 6-13 amino acids that includes a FVIII 6-amino-acid fragment). See also para 73.
Wraith also teaches compositions in which peptides therein “may each comprise a different minimal epitope”, para 113, and also that a peptide “may comprise a plurality of peptides, for example, two, three, four, five or six peptides of the invention,” para 112, and that are in compositions that include excipients which are pharmaceutically suitable, para 131, however does not teach multiple different peptides (re “at least two derived from FVIII”) in a compound also comprising a biopolymer scaffold.
The level of ordinary skill in the art is high.
LS teaches “Induction of tolerance to factor VIII inhibitors by gene therapy with immunodominant A2 and C2 domains presented by B cells as Ig fusion proteins,” Title, see also Abstract and Introduction. On page 4870 LS summarizes, “In sum, we have demonstrated that B-cell presentation of both fVIII domains on an Ig backbone via a retroviral gene therapy protocol is a very effective therapeutic to block the total immune response to fVIII in naive as well as in fVIII-primed recipients.”
In that using an Ig biopolymer to join two FVIII conformational epitope peptides on the exposed surfaces of C2 and A2 of FVIII, selected for their immunodominance, toward induction of tolerance, was “very effective” (this based on the expression of such construct), one of ordinary skill in the art would have been motivated to improve the use of the Wraith-taught core residue sequences of its Table 2 by joining them to a biopolymer such as Ig. This is an improvement taught by LS and readily implemented given the similar nature of what is being sought to be improved upon regarding tolerance to FVIII in hemophiliac subjects. There would have been a reasonable expectation of success at least given the data from LS.
Accordingly, it would have been obvious to one of ordinary skill in the art to join two different peptides of Wraith with an Ig biopolymer as taught by LS, the results would have been predictable, and based on the above claim 14 would have been obvious.
Claim 16 also would have been obvious because the clear objective of both Wraith and LS is to reduce the inhibition of FVIII due to antibodies formed in the individual in response to the administration of FVIII, and there is data and/or support for achieving such effect – inhibiting neutralization of the factor VIII replacement product, in both cited references.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOSEPH FISCHER whose telephone number is (571)270-7925, and whose direct facsimile number is (571)270-8925. The examiner can normally be reached on Monday to Friday, 9:00 AM to 5:00 PM, however noting that the examiner will not normally be working on Monday/Tuesday and on Wednesday-Friday on alternating weeks, but will promptly answer messages upon his return to work.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Melissa Fisher can be reached on 571-270-7430. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JOSEPH FISCHER/Primary Examiner, Art Unit 1658
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