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 .
DETAILED ACTION
2. Claims 1 – 8, 11 – 16, and 18 – 19 are pending this application. Applicant’s preliminary amendment, submitted March 28, 2024, is entered, wherein claims 1 – 8 and 11 – 16 are amended, claims 18 – 19 are new, and claims 9 – 10 and 17 are canceled.
Claims 1 – 8, 11 – 16, and 18 – 19 are examined on merits herein.
Priority
3. This application is a national stage application of PCT/CN2022/122560, filed September 29, 2022, which claims benefit of foreign priority document CN202111152832.1, filed September 29, 2021.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 04/01/2024 was filed in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
The information disclosure statement filed 01/27/2025 fails to comply with the provisions of 37 CFR 1.98(a)(4) because it lacks the appropriate size fee assertion. It has been placed in the application file, but the information referred to therein has not been considered as to the merits.
Claim Objections
Claims 1 – 2, 4 – 8, and 12 – 14 are objected to because of the following informalities:
Claim 1, line 13, “where” should read “wherein”.
Claim 1, line 14, “and” should be inserted immediately after “proline;”.
Claim 1, line 16, “or” immediately after “hydrogen,” should be removed.
Claim 1, line 18, “and” should be inserted immediately after “C1-C6 alkyl;”.
Claim 1, line 19, “,” should be inserted immediately after “alkoxy”.
Claim 2, line 7, “,” should be inserted immediately after “alkynyloxy”.
Claim 2, line 9, “,” should be inserted immediately after “alkanoyloxy”.
Claim 2, line 9, “are” immediately after “aryloxy” should be replaced by “is/are”.
Claim 2, line 11, “,” should be inserted immediately after “propionyl”.
Claim 2, line 14, “and” should be inserted immediately after “proline;”.
Claim 2, line 16, “is” immediately after “aryloxy” should be replaced by “is/are”.
Claim 2, line 17, “,” should be inserted immediately after “cyano”.
Claim 2, line 20, “is” immediately after “alkanoyl” should be replaced by “is/are”.
Claim 2, line 21, “,” should be inserted immediately after “propionyl”.
Claim 2, line 22, “,” should be inserted immediately after “R12”.
Claim 2, line 25, “is” immediately after “alkyl” should be replaced by “is/are”.
Claim 2, line 27, “,” should be inserted immediately after “propionyl”.
Claim 2, line 28, “and” should be inserted immediately after “nitro;”.
Claim 2, line 30, “;” immediately after “aryloxy” should be replaced by “,”.
Claim 2, line 31, “is” immediately after “aryloxy” should be replaced by “is/are”.
Claim 2, line 32, “,” should be inserted immediately after “cyano”.
Claim 4, line 3, “R15” should read “R15”.
Claim 4, line 3, “and” should be inserted immediately after “proline;”.
Claim 5, line 2, “;” immediately after “alkanoyl” should read “,”.
Claim 5, line 4, “is” immediately after “alkanoyl” should be replaced by “is/are”.
Claim 5, line 4, “,” should be inserted immediately after “propionyl”.
Claim 6, lines 2 and 4, “,” should be inserted immediately after “R12”.
Claim 7, line 2, “,” immediately after “OH” should be removed.
Claim 8, line 3, “and/or” immediately after “E2;” should be removed.
Claim 12, line 10, “,” immediately after “wherein” should be removed.
Claim 12, line 12, “,” should be inserted immediately after “alkynyloxy”.
Claim 12, line 14, “,” should be inserted immediately after “alkanoyloxy”.
Claim 12, lines 14, “are” immediately after “aryloxy” should be replaced by “is/are”.
Claim 12, line 16, “,” should be inserted immediately after “propionyl”.
Claim 12, line 18, “and” should be inserted immediately after “proline;”.
Claim 12, line 20, “is” immediately after “aryloxy” should be replaced by “is/are”.
Claim 12, line 21, “,” should be inserted immediately after “cyano”.
Claim 12, line 23, “,” immediately after “wherein” should be removed.
Claim 12, line 24, “is” immediately after “alkanoyl” should be replaced by “is/are”.
Claim 12, line 25, “,” should be inserted immediately after “propionyl”.
Claim 12, line 27, a space and “,” should be inserted immediately after “R12’”.
Claim 12, line 27, “,” immediately after “hydrogen” should be removed.
Claim 12, line 29, “is” immediately after “alkanoyl” should be replaced by “is/are”.
Claim 12, line 31, “,” should be inserted immediately after “propionyl”.
Claim 12, line 35, “is” immediately after “aryloxy” should be replaced by “is/are”.
Claim 12, line 36, “,” should be inserted immediately after “cyano”.
Claim 13, line 3, “and/or” immediately after “isopropoxy;” should be removed.
Claim 13, line 5, “R15” should read “R15”.
Claim 13, line 5, “and” should be inserted immediately after “proline;”.
Claim 13, line 6, “,” should be inserted immediately after “methoxy”.
Claim 13, line 7, “and/or” immediately after “residue” should be removed.
Claim 13, line 10, “is” immediately after “alkanoyl” should be replaced by “is/are”.
Claim 13, line 11, “,” should be inserted immediately after “propionyl”.
Claim 13, line 12, “and/or” immediately after “trifluoroacetyl;” should be removed.
Claim 13, line 13, “,” should be inserted immediately after “R12’”.
Claim 13, line 17, “,” immediately after “OH” should be removed.
Claim 14, line 3, “or” immediately after the structure of CP-1 should be removed.
Claim 14, lines 4, 6, and 8, “formula (I’) is” should be removed.
Appropriate correction is required.
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 3 – 8 and 13 – 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.
a. Claims 3 – 8 and 13 recite the term “preferably”. These claims are indefinite because the inclusion of the term “preferably” renders the scope of the claims ambiguous. The use of “preferably” introduces uncertainty as to whether the narrower range is intended to be a required limitation of merely a suggested, non-limiting embodiment of the broader range. The use of term prevents one of ordinary skill in the art from determining the precise boundaries of the claims. Claims 14 – 16 depend from claim 13 are also indefinite. Under the broadest reasonable interpretation, the term “preferably” do not impose a limitation on the claim scope. Therefore, the actual limitation will be the recitation preceding the first use of “preferably”.
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 – 8, 11, and 18 – 19 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method of treating inflammation, does not reasonably provide enablement for a method of preventing inflammation. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims. Claims 2 – 8, 11, and 18 – 19 depend from claim 1.
The Applicant’s attention is drawn to re Wands, 8 USPQ2d 1400 (CAFC1988) at 1404 where the court set forth eight factors to consider where assessing if a disclosure would have required undue experimentation. Citing Ex parte Forman, 230 USPQ 546 (BdApls 1986) at 547 the court recited eight factors:
(1) The nature of the invention;
(2) the state of the prior art;
(3) the relative skill of those in the art;
(4) the predictability or unpredictability of the art;
(5) the breadth of the claims;
(6) the amount of direction or guidance presented;
(7) the presence or absence of working examples; and
(8) the quantity of experimentation necessary.
The nature of the invention & The breadth of claims:
The claimed invention is directed to a method of preventing or treating inflammation. In order to be enabled for the full scope of the method, one skilled in the art must reasonably be able to ascertain which compositions are effective to prevent inflammation. Moreover, “preventing” inflammation including administering the claimed formulation to a subject not suffering from inflammation in such a manner that the subject does not experience inflammation in the future.
The state of prior art:
While there are publications that describe methods of treating inflammation, there is no evidence in the prior art that the claimed composition would prevent inflammation from ever occurring. For example, Vessella et al. (Organic & Biomolecular Chemistry, 2019, Vol. 17, Issue 12, page 3129 – 3140, See PTO-892) teach a synthesis of the tetrasaccharide repeating unit of the cryoprotectant capsular polysaccharide from Colwellia psychrerythraea 34H (Title). Colwellia psychrerythraea 34H is a psychrophilic Gram-negative bacterium that is able to survive at subzero temperatures by producing a unique capsular polysaccharide (CPS) with anti-freeze properties similar to those of the well-known anti-freeze (glycol)proteins (Abstract). Vessella et al. teach compound 1 (page 3130, Scheme 1):
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Carillo et al. (Journal of the American Chemical Society, 2014, Vol. 137, Issue 1, page 179 – 189, See PTO-892) teach the CPS from Colwellia psychrerythraea 34H and discuss that the structural features of this unique polysaccharide resemble those present in antifreeze proteins and glycoproteins (Abstract).
Zheng et al. (Frontiers in Pharmacology, 2020, Vol. 11, See PTO-892) teach that a bacterial CPS may be administered to treat intestinal inflammation. Zheng et al. disclose TP2, a zwitterionic CPS extracted from Bacteroides fragilis ZY-312, and explain that CPS can have immune activity because their structure vary in sugar composition, ring form, linkage position, and isomeric form (page 2, Left Col., para. 2). Zheng et al. further teach that TP2 has a repeating unit consisting of four monosaccharides and that the study confirms the anti-inflammatory ability of TP2 in DNBS-induced colitis model (page 2, Right Col., para. 1). Zheng et al. administer TP2 after enteritis induction at 1.25, 2.5, and 5 mg/kg for seven consecutive days, and report that TP2 significantly alleviate enteritis, reduce intestinal adhesions, reduce ulcer area, and reduce ulcer incidence, with 2.5 mg/kg identified as the optimal dose (page 4, Right Col., para. 2). Zheng et al. also report that TP2 mainly remains in the digestive tract, especially the cecum and colorectum, and exists in prototype/undegraded form (page 5, Right Col., para. 2), which supports that polysaccharide itself exerts the biological effect.
Heisig et al. (PLOS ONE, 2015, Vol. 10, Issue 2, See PTO-892) teach that an anti-freeze glycoprotein has anti-inflammatory activity in a mammalian inflammatory model. Specifically, Heisig et al. disclose a transgenic mouse model expressing Ixodes scapularis anti-freeze glycoprotein (IAFGO) and report that macrophages from IAFGP-transgenic mice, after LPS stimulation, released lower levels of inflammatory mediators including IL-6 and TNF-α than control cells. Heisig et al. explicitly state that IAFGP-expression reduces inflammation and that induction of inflammatory cytokines after LPS stimulation is 2-fold to 16-fold lower in transgenic cells than in wild-type cells (page 5, para. 1; Figure 3).
Thus, the cited prior art references collectively teach that Colwellia psychrerythraea 34H CPS resemble the structural features present in antifreeze proteins and glycoproteins and that antifreeze glycoprotein has anti-inflammatory effect by reducing inflammatory cytokine, but the cited prior art references never teach prevention of inflammation.
The relative skill of those in the art:
The relative skill of those in the art is high.
The predictability or unpredictability of the art:
According to Zheng et al. and Heisig et al., inflammation may arise from different biological causes, disease states, tissues, and immune triggers. Zheng et al. discuss intestinal inflammation or ulcerative colitis and use a DNBS-induced enteritis model, while Heisig et al .discuss inflammation associated with frostbite/cold injury and LPS-stimulated macrophages. Thus, the prior art show that inflammation is not a single predictable condition, but rather a broad biological response that may occur in different tissues and under different pathological circumstances.
The wide range of possible inflammatory etiologies make it difficult to predict which subjects will develop inflammation in the future, what type of inflammation will occur, when the inflammatory response will begin, and whether administration of the claimed bacterial capsular oligosaccharide derivative before onset would actually prevent inflammation. Medications for inflammation are generally administered to subjects already displaying signs or symptoms of inflammation, or to subjects in defined experimental disease models, rather than to healthy or asymptomatic subjects who merely might develop inflammation in the future. Therefore, the art is unpredictable with respect to preventing inflammation.
The amount of direction or guidance presented & The presence or absence of working examples:
The specification provides some direction for evaluating anti-inflammatory activity of selected disclosed compounds. For example, Test Example 1 describes in vitro assays using RAW 264.7 cells treated with compounds CP-1 and CP-2, followed by stimulation with 100 ng/mL LPS for 24 hours. The specification reports that CP-1 and CP-2 inhibit LPS-induced release of nitric oxide and prostaglandin E2 in a dose-dependent manner, and also inhibit LPS-induced release of IL-1β, IL-6, and TNF-α in RAW 264.7 cells. Test Example 2 further reports that CP-1 and CP-2 inhibit LPS-induced intracellular iNOS and COX-2 protein expression in RAW 264.7 cells. The specification also provides limited in vivo examples in LPS-induced mouse models. Test Example 3 describes administration of CP-1 in an LPS-induced sepsis mouse model, including administration before LPS modeling and after LPS modeling, and reports survival rate and cytokine results. The specification also describes CP-Me administration in an LPS-induced sepsis mouse model and measurement of IL-1β, IL-6, and TNF-α. The specification further describes HE staining and inflammatory index analysis of LPS-induced lung injury and reports that CP-1 alleviates lung injury caused by LPS.
However, these working examples provide guidance for evaluating anti-inflammatory activity in response to a known and intentionally induced inflammatory stimulus, namely LPS. The working examples do not provide sufficient guidance for practicing the claimed method of preventing inflammation in an individual before inflammation occurs. In the examples, the inflammatory trigger is known, controlled, and induced. In actual preventive treatment, the specification does not teach how to determine which individual is likely to develop inflammation, what inflammatory trigger will occur, when the inflammatory response will begin, or when administration should be started to prevent the inflammatory response from occurring.
The quantity of experimentation necessary:
In order to carry out the claimed preventative treatment, one of ordinary skill in the art would need to develop specifically preventative treatment from scratch with no assistance from Applicant’s declaration beyond the general idea that the claimed composition is capable of treating inflammation. Because inflammation is caused by multiple factors as mentioned above, determining which healthy patients would benefit from this treatment would be difficult and unpredictable based on the state of the art, and any treatment is likely to be imperfectively effective given the influence of other factors..
Genentech, 108 F.3d at 1366, states that “a patent is not a hunting license. It is not a reward for search, but compensation for its successful conclusion.” And “patent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable.”
Therefore, in view of the Wands factors, as discussed above, particularly the state of art and the lack of guidance or working examples, Applicant fails to provide information sufficient to practice the claimed invention.
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.
Claim 19 is 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. Claim 19 depends on claim 18. Claim 18 recites the method of claim 1, wherein the derivative is selected from Compound CP-1, Compound CP-Me, Compound CP-Et, or Compound CP-Pr. Claim 19, however, recites that the derivative is Compound CP-2. Because CP-2 is not included among the derivative recited in claim 18, claim 19, therefore, does not further limit claim 18. 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 Rejections - 35 USC § 103
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.
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:
i. Determining the scope and contents of the prior art.
ii. Ascertaining the differences between the prior art and the claims at issue.
iii. Resolving the level of ordinary skill in the pertinent art.
iv. 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.
Claims 1 – 8 and 18 – 19 are rejected under 35 U.S.C. 103 as being unpatentable over Vessella et al. (Organic & Biomolecular Chemistry, 2019, Vol. 17, Issue 12, page 3129 – 3140, See PTO-892) in view of Carillo et al. (Journal of the American Chemical Society, 2014, Vol. 137, Issue 1, page 179 – 189, See PTO-892), Zheng et al. (Frontiers in Pharmacology, 2020, Vol. 11, See PTO-892), and Heisig et al. (PLOS ONE, 2015, Vol. 10, Issue 2, See PTO-892).
a. Vessella et al. teach a synthesis of the tetrasaccharide repeating unit of the cryoprotectant capsular polysaccharide from Colwellia psychrerythraea 34H (Title). Colwellia psychrerythraea 34H is a psychrophilic Gram-negative bacterium that is able to survive at subzero temperatures by producing a unique capsular polysaccharide (CPS) with anti-freeze properties similar to those of the well-known anti-freeze (glycol)proteins (Abstract). Vessella et al. teach compound 1 (page 3130, Scheme 1):
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which corresponds to the claimed bacterial CPS derivative of formula I, wherein R1 is an unsubstituted C3 alkoxy; R2 is -N(H)-R15, wherein R15 is an amino acid residue; R3 and R4 are C1 alkanoyl; R5 – R13 are hydrogen; and R14 is OH. Thus, Vessella et al. teach compound 1, which reads on the limitations the structure of formula I along with the R substituents of claims 1 – 7. Vessella et al. disclose the synthesis of compound 1 (page 3133, Scheme 7):
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which show that compound 36 with R2’ = OH is achieved. Thus, Vessella et al. teach the same Colwellia psychrerythraea 34H CPS scaffold as CP-Et recited in claim 14, including the amino sugar residues, uronic acid residues, N-acetyl groups, and threonine amide substituent. Compound 1 of Vessella et al. differs from CP-Et primarily at the reducing-end anomeric substituent, where Vessella et al. disclose an propoxy and CP-Et contains the corresponding ethoxy group.
However, Vessella et al. do not teach a method of treating inflammation, wherein the method comprises administering to an individual in need thereof a therapeutically effective amount of the claimed bacterial capsular oligosaccharide derivative. Vessella et al. do not teach that anti-inflammatory means the activities recited in claim 8. Vessella et al. also do not teach the process for preparing the derivative.
Carillo et al. teach the CPS from Colwellia psychrerythraea 34H and discuss that the structural features of this unique polysaccharide resemble those present in antifreeze proteins and glycoproteins (Abstract). Carillo et al. further disclose that the antifreeze glycoprotein (AFGPs) isolated from fish blood plasma consist of a regular tripeptide sequence of Ala-Ala-Thr with a disaccharide (β-D-galactosyl-(1 – 3)-α-D-galactosamine) linked to the threonine residue. Thus, Carillo et al. identify the antifreeze glycoprotein class being compared and teach that the Colwellia CPS has antifreeze-glycoprotein-like structural features.
Zheng et al. teach that a bacterial CPS may be administered to treat intestinal inflammation. Zheng et al. disclose TP2, a zwitterionic CPS extracted from Bacteroides fragilis ZY-312, and explain that CPS can have immune activity because their structure vary in sugar composition, ring form, linkage position, and isomeric form (page 2, Left Col., para. 2). Zheng et al. further teach that TP2 has a repeating unit consisting of four monosaccharides of 2,4-dideoxy-4-amino-D-N-acetylfucose, D-N-acetylgalactosamine, D-galactopyranose, and D-galactofuranose with 4,6-pyruvate attached to the galactopyranose. and that the study confirms the anti-inflammatory ability of TP2 in DNBS-induced colitis model (page 2, Right Col., para. 1). Thus, Zheng et al. teach the features of the bacterial capsular polysaccharides, including tetrasaccharide repeating units, amino sugars residues, N-acetylated sugar residues, galactose-type residues, and charged functionality, that possess anti-inflammatory activity. Zheng et al. administer TP2 after enteritis induction at 1.25, 2.5, and 5 mg/kg for seven consecutive days, and report that TP2 significantly alleviate enteritis, reduce intestinal adhesions, reduce ulcer area, and reduce ulcer incidence, with 2.5 mg/kg identified as the optimal dose (page 4, Right Col., para. 2). Zheng et al. also report that TP2 mainly remains in the digestive tract, especially the cecum and colorectum, and exists in prototype/undegraded form (page 5, Right Col., para. 2), which supports that polysaccharide itself exerts the biological effect.
Heisig et al. teach background regarding AFGPs, including that AFGPs are a class of antifreeze proteins and that their primary amino acid sequence consists of canonical Ala-Ala-Thr or Pro-Ala-Thr repeats with β-D-galactosyl-(1[Wingdings font/0xE0]3)-α-N-acetyl-D-galactosamine disaccharides attached to each threonine (page 2, para. 1). Heisig et al. further identify a specific AFGP from Ixodes scapularis, namely Ixodes scapularis anti-freeze glycoprotein (IAFGP) and report that macrophages from IAFGP-transgenic mice, after LPS stimulation, released lower levels of inflammatory mediators including IL-6 and TNF-α than control cells. Heisig et al. explicitly state that IAFGP-expression reduces inflammation and that induction of inflammatory cytokines after LPS stimulation is 2-fold to 16-fold lower in transgenic cells than in wild-type cells (page 5, para. 1; Figure 3). Thus, Heisig et al. teach that anti-freeze glycoprotein activity is associated with reduced inflammatory cytokine release in mammalian cells.
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to administer a therapeutically effective amount of the bacterial capsular oligosaccharide derivative as taught by Vessella et al. for treating inflammation because Carillo et al. teach that Colwellia psychrerythraea 34H capsular polysaccharide has structural features resembling those present in antifreeze proteins and glycoproteins and Heisig et al. teach that AFGPs consists of canonical Ala-Ala-Thr or Pro-Ala-Thr repeats with β-D-galactosyl-(1[Wingdings font/0xE0]3)-α-N-acetyl-D-galactosamine disaccharides attached to each threonine and antifreeze glycoprotein activity is associated with anti-inflammatory activity in mammalian cells, including reducing inflammatory cytokine release after KPS stimulation. One would have been motivated to evaluate the known antifreeze-glycoprotein-like Colwellia psychrerythraea 34H CPS of Vessella et al. for reducing inflammation because Carillo et al. teach that Colwellia psychrerythraea 34H capsular polysaccharide has structural features resembling those present in antifreeze proteins and glycoproteins and Heisig et al. teach that antifreeze glycoprotein activity is associated with anti-inflammatory activity in mammalian cells, including reducing inflammatory cytokine release after KPS stimulation. Zheng et al. further provide motivation because Zheng et al. teach that bacterial CPS may be administered in vivo to treat inflammatory intestinal disease. Zheng et al. disclose that TP2, a bacterial CPS from Bacteroides fragilis, significantly alleviated enteritis and reduced intestinal adhesion, ulcer area, and ulcer incidence after administration to rats. One of ordinary skill in the art would have had a reasonable expectation of success to administer a therapeutically effective amount of the bacterial capsular oligosaccharide derivative as taught by Vessella et al. for treating inflammation because Vessella et al. and Carillo et al. teach the specific Colwellia psychrerythraea 34H capsular oligosaccharide scaffold and its antifreeze-glycoprotein-like character, Heisig et al. teach that antifreeze glycoprotein activity reduces inflammatory cytokine release in mammalian cells, and Zheng et al. teach that bacterial CPS may be administered to treat intestinal inflammation. Thus, the combination of references would have provided a reasonable expectation that the known Colwellia psychrerythraea 34H CPS would be useful for treating inflammation.
With respect to claim 8, Vessella et al. teach the same Colwellia psychrerythraea 34H CPS, Carillo et al. teach its antifreeze-glycoprotein-like character, Heisig et al. provide motivation to use antifreeze-glycoprotein-like activity for reducing inflammation, and Zheng et al. provide motivation to administer bacterial CPS for treating inflammation. As the method of administering the same or obvious derivative for treating inflammation is rendered obvious, the reduction of the particular inflammatory biomarker recited in claim 8, including reduction of IL-1β , IL-6, and TNF-α, will be necessarily present.
With respect to claim 18, it would have been prima facie obvious for a person of ordinary skill I the art before the effective filing date of the claimed invention to substitute propoxy of the CPS derivative as taught by Vessella et al. to ethoxy because it has long been established that this type of difference, which is varying the size of a chain, constitutes a form of homology, and is a fact of very close structural similarity, rending the homolog obvious. As was stated in In re Grose, 201 USPZ 57, 63, “The known structural relationship between adjacent homologues, for example, supplies a chemical theory upon which a prima facie case of obviousness of a compound may rest.” See specifically In re Shetty, 195 USPQ 753; In re Wilder, 195 USPQ 426 and Ex Parte Greshem, 121 USPQ 422, all of which feature a compound with a C2 link rejected over a compound with a C1 link. Similarly, In re Chupp, 2 USPQ2d 1437 and In re Coes, 81 USPQ 369 have a compound with a C1 link unpatentable over prior art showing C2 link. Note Ex parte Agouridas, 65 USPQ2d 1142, where a C4 chain was held obvious over a C3 chain. Note also In re Schaub, 190 USPQ 324, 326, where compounds with C5 and C6 chains were called “adjacent homologs in the classic sense”. Ex parte Ruddy, 121 USPQ 427 has a C3 link unpatentable over a C1 link. Ex parte Nathan, 121 USPQ 349 found the insertion of a C2H4 link obvious. In all of these cases, the variation was found to be obvious on the basis of close structural similarity; no secondary teaching was employed. As was stated directly in THE GENERAL TIRE & RUBBER COMPANY v. JEFFERSON CHEMICAL COMPANY, INC., 182 USPQ 70 (1974): “If any structural change is obvious to one skilled in the art, a substitution of the next higher homolog would seem to be.” Note also In re Jones, 21 USPQ2d 1942, which states at 1943 “Particular types or categories of structural similarity without more, have, in past cases, given rise to prima facie obviousness”; one of those listed is “adjacent homologues and structural isomers”. Similar is In re Schechter and LaForge, 98 USPQ 144, 150, which states “a novel useful chemical compound which is homologous or isomeric with compounds of the prior art is unpatentable unless it possesses some unobvious or unexpected beneficial property not possessed by the prior art compounds.” Note also In re Deuel, 34 USPQ2d 1210, 1214 which states, “Structural relationships may provide the requisite motivation or suggestion to modify known compounds to obtain new compounds. For example, a prior art compound may suggest its homologs because homologs often have similar properties and therefore chemists of ordinary skill would ordinarily contemplate making them to try to obtain compounds with improved properties.” Therefore, one of the ordinary skill in the art would have had a reasonable expectation of success to propoxy of the CPS derivative as taught by Vessella et al. to ethoxy because it is known in the art that homologs often have similar properties and the result is predictable.
For the “R2’” limitation of claim 18, Vessella et al. further teach compound 36 in Scheme 7, wherein X is COOH, corresponding to the carboxylic acid form before conversion to the threonine amide. Thus, Vessella et al. teach both the same tetrasaccharide scaffold and the carboxylic acid form relevant to CP-Et. It would have been obvious to retain the carboxylic acid form taught by compound 36 and to use the ethoxy homolog at the R1’ position in place of the propoxy group of compound 1 because these changes represent routine selection of closely related carbohydrate derivatives.
Regarding claim 19, it would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to prepare CP-2 as the corresponding reducing-end hydroxy analog of compound 1 disclosed by Vessella et al. because Vessella et al. teach the same Colwellia psychrerythraea 34H CPS scaffold, including the amino sugar residues, uronic acid residues, N-acetyl groups, and threonine amide substituent. CP-2 differs from compound 1 primarily in that CP-2 contains a hydroxy group at the claimed R1’ position. The hydroxy group represents the conventional reducing-end form of a carbohydrate, and replacement of the terminal propoxy with hydroxy would have been a routine modification that preserves the same biologically relevant Colwellia psychrerythraea 34H CPS core. Therefore, one of ordinary skill would have had a reasonable expectation to prepare CP-2 as the corresponding reducing-end hydroxy analog of compound 1 disclosed by Vessella et al. because CP-2 would have been an obvious close structural variant of compound 1.
Claim 11 is rejected under 35 U.S.C. 103 as being unpatentable over Vessella et al. (Organic & Biomolecular Chemistry, 2019, Vol. 17, Issue 12, page 3129 – 3140, See PTO-892) in view of Carillo et al. (Journal of the American Chemical Society, 2014, Vol. 137, Issue 1, page 179 – 189, See PTO-892), Zheng et al. (Frontiers in Pharmacology, 2020, Vol. 11, See PTO-892), and Heisig et al. (PLOS ONE, 2015, Vol. 10, Issue 2, See PTO-892) as applied to claims 1 – 8 and 18 – 19 above, further in view of Despras et al. (Angewandte Chemie International Edition, 2014, Vol. 53, Issue 44, page 11912 – 11916), Ramadan et al. (ACS Central Science, 2020, Vol. 6, Issue 6, page 913 – 920, PTO-892), and Santra (Beilstein Journal of Organic Chemistry, 2011, Vol. 7, page 1182 – 1188, PTO-892).
b. Vessella et al., Carillo et al., Zheng et al., and Heisig et al. teach the limitations discussed above. Vessella et al. further teach synthesis of the Colwellia psychrerythraea 34H CPS tetrasaccharide scaffold using protected carbohydrate donor and acceptor fragments. Vessella et al. disclose (page 3132, Scheme 5):
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wherein glycosylating protected disaccharide acceptor 22 with protected monosaccharide glucosyl donor 4 or 25 to form protected trisaccharide 23, followed by selective deprotection to provide trisaccharide acceptor 24. Thus, Vessella et al. teach that the Colwellia psychrerythraea 34H CPS scaffold may be assembled using protected saccharide donor/acceptor fragments and sequential glycosylation/deprotection steps. The protected disaccharide acceptor 22 represents the same carbohydrate backbone as claimed disaccharide I-13, only differing in its temporary protecting group pattern. The use of different protecting groups would have been obvious to one of ordinary skill in the carbohydrate synthesis because protecting groups are temporary synthetic handles routinely selected to control glycosylation reactivity, stereoselectivity, solubility, and orthogonal deprotection.
However, Vessella et al., Carillo et al., Zheng et al., and Heisig et al. do not teach preparing the complementary GlcA-containing disaccharide as the claimed 2-trifluoromethyl oxazoline glycosyl donor (I-18) and coupling complementary disaccharide fragments I-13 and I-18 in a convergent [2 + 2] glycosylation to obtain protected tetrasaccharide I-19.
Despras et al. teach synthesis of size-defined chitooligosaccharides using activated trifluoromethyl oxazoline oligomeric donors (Abstract). Despras et al. disclose that stable trifluoromethyl oxazolines have been selected as glycosyl donors and oxazoline dimer donor 13 has been evaluated in glycosylation with dimer acceptors (page 11913, Right Col., para. 1). Despras et al. disclose that oxazoline dimer donor 13 (page 11913, Scheme 2; page 11914, Scheme 3):
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345
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is reacted with dimer acceptor 11 under catalytic TMSOTf conditions to provide tetrasaccharide 17 in good yield of 82%. Despras et al. further disclose that the same glycosylation condition using donor 13 and acceptor 12 provided tetrasaccharide 18 in 78% yield (page 11913, Right Col., para. 2), showing that trifluoromethyl oxazoline dimer donors are effective protective disaccharide donors for preparing protected tetrasaccharides. Despras et al. additionally state that these oxazoline donors are reactive donors, just as the trichloromethyl counterparts (page 11913, Right Col., para. 2). Thus, Despras et al. teach that a protected disaccharide oxazoline donor may be coupled with a protected disaccharide acceptor to obtain a protected tetrasaccharide. Despras et al. disclose the preparation of protected disaccharide oxazoline donor 13 and demonstrate that the oxazoline donor reacts with a protected disaccharide acceptor to provide protected tetrasaccharides 17 and 18. The disclosed oxazoline donor comprises a protected disaccharide having a reducing-end N-trifluoroacetyl glucosamine converted into a 2-trifluoromethyl oxazoline glycosyl donor. Thus, Despras et al. teach preparation and use of protected 2-trifluoromethyl oxazoline disaccharides as activated glycosyl donors and demonstrate that such oxazoline donors may be coupled with protected disaccharide acceptors to prepare protected tetrasaccharides. Accordingly, Despras et al. establish that protected trifluoromethyl oxazoline disaccharides are stable and reactive glycosyl donors suitable for convergent disaccharide-disaccharide glycosylation.
Ramadan et al. teach that 24-mer 1 can be obtained from the fully protected precursor 24-mer 2 (page 914, Scheme 1):
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which in turn can be generated using disaccharide building blocks 3 and 4 (page 914, Left Col., para. 1). Ramadan et al. further disclose that, to overcome the challenges with TFA-protected disaccharide donors, the reactivities of building blocks can be enhanced by using less electron withdrawing protective groups such as trichloroacetyl (TCA) and benzyl groups (page 914, Right Col., para. 3). Ramadan et al. disclose that glycosylation of disaccharide donor 17 with acceptor 18 resulted in formation of disaccharide oxazoline 19 as the major product (page 915, Figure 2):
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.
Disaccharide oxazoline 19 exists in the trifluoromethyl oxazoline form and structurally corresponds to the claimed oxazoline donor I-18. Thus, Ramadan et al. teach that a protected GlcA-containing disaccharide may be converted into a protected 2-trifluoromethyl oxazoline derivative (disaccharide oxazoline 19), providing a close structural analogue of claimed oxazoline donor I-18. The use of different protecting groups would have been obvious to one of ordinary skill in the carbohydrate synthesis because protecting groups are temporary synthetic handles routinely selected to control glycosylation reactivity, stereoselectivity, solubility, and orthogonal deprotection.
Santra teaches an convenient synthesis of the tetrasaccharide repeating unit of the O-antigen of Shigella boydii type 9 using a [2 + 2] block glycosylation strategy, wherein such strategy has achieved excellent yield (Abstract). Santra discloses preparation of protected disaccharide building blocks (page 1184, Schemes 1 and 2):
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and then coupling protected disaccharide 2 with protected disaccharide 7 to obtain protected tetrasaccharide 8. Santra reports that the disaccharide-disaccharide coupling is carried out using N-iodosuccinimide and HClO4-SiO2 and afforded the protected tetrasaccharide in 82% yield (page 1184, Scheme 3). Thus, Santra teaches that protected tetrasaccharides may be efficiently prepared by coupling two protected disaccharide fragments in a convergent [2 + 2] glycosylation approach.
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the synthesis of the Colwellia psychrerythraea 34H CPS tetrasaccharide scaffold taught by Vessella et al. by preparing the complementary GlcA-containing disaccharide as the corresponding 2-trifluoromethyl oxazoline form in view of Despras et al. and Ramadan et al. because Ramadan et al. disclose formation of protected GlcA-containing disaccharide oxazoline 19, thereby establishing that a disaccharide having the relevant GlcA-containing backbone is capable of forming a 2-trifluoromethyl oxazoline and Despras et al. teach that protected 2-trifluoromethyl oxazoline disaccharides constitute known glycosyl donors for oligosaccharide synthesis. One of ordinary skill in the art would have been motivated to modify the synthesis of the Colwellia psychrerythraea 34H CPS tetrasaccharide scaffold taught by Vessella et al. by preparing the complementary GlcA-containing disaccharide as the corresponding 2-trifluoromethyl oxazoline form in view of Despras et al. and Ramadan et al. because conversion of the complementary GlcA-containing disaccharide into the 2-trifluoromethyl oxazoline form would provide an activated anomeric donor suitable for the subsequent glycosylation required to assemble the known tetrasaccharide scaffold of Vessella et al. and Despras et al. specifically teach that trifluoromethyl oxazoline disaccharide are reactive donors that may be coupled with protected carbohydrate acceptors to form higher oligosaccharides. One would also have been motivated to use the oxazoline form of the disaccharide donor because Despras et al. teach that trifluoromethyl oxazolines are selected as glycosyl donors after donor-forming reactions produced oxazoline species and Despras et al. further teach that such oxazoline donors are stable, reactive, and effective in glycosylation reactions. Thus, Despras et al. teach that oxazoline disaccharide donors are useful activated glycosyl donors for forming higher oligosaccharides. One of ordinary skill in the art would have had a reasonable expectation of success to modify the synthesis of the Colwellia psychrerythraea 34H CPS tetrasaccharide scaffold taught by Vessella et al. by preparing the complementary GlcA-containing disaccharide as the corresponding 2-trifluoromethyl oxazoline form in view of Despras et al. and Ramadan et al. because Ramadan et al. demonstrate that the relevant GlcA-containing protected disaccharide backbone may form the corresponding 2-trifluoromethyl oxazoline structure and Despras et al. demonstrate that protected disaccharide trifluoromethyl oxazolines successfully function as glycosyl donors under established glycosylation conditions.
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to further modify the synthesis of the Colwellia psychrerythraea 34H CPS tetrasaccharide scaffold taught by Vessella et al. by coupling the protected 2-trifluoromethyl oxazoline disaccharide donor with the complementary protected disaccharide acceptor through a convergent protected disaccharide-protected disaccharide [2 + 2] glycosylation in view of Santra to obtain tetrasaccharide I-19 from disaccharide I-13 and disaccharide I-18 because Vessella et al. teach the desired Colwellia psychrerythraea 34H CPS tetrasaccharide scaffold and demonstrate that the scaffold may be assembled using protected carbohydrate donor and acceptor fragments, Despras et al. teach that activated trifluoromethyl oxazoline oligomeric donors are useful glycosyl donors and specifically how coupling an oxazoline dimer donor with dimer acceptors to provide tetrasaccharides, and Santra further teach that protected tetrasaccharides may be efficiently prepared by coupling two protected disaccharide fragments in a convergent [2 + 2] glycosylation. One would have been motivated to modify the synthesis of the Colwellia psychrerythraea 34H CPS tetrasaccharide scaffold taught by Vessella et al. by coupling the protected 2-trifluoromethyl oxazoline disaccharide donor with the complementary protected disaccharide acceptor through a convergent protected disaccharide-protected disaccharide [2 + 2] glycosylation in view of Santra to obtain tetrasaccharide I-19 from disaccharide I-13 and disaccharide I-18 because such [2 + 2] glycosylation strategies are known to provide protected tetrasaccharides from protected disaccharide building blocks. One of ordinary skill would have had a reasonable expectation of success to modify the synthesis of the Colwellia psychrerythraea 34H CPS tetrasaccharide scaffold taught by Vessella et al. by coupling the protected 2-trifluoromethyl oxazoline disaccharide donor with the complementary protected disaccharide acceptor through a convergent protected disaccharide-protected disaccharide [2 + 2] glycosylation in view of Santra because Vessella et al. teach the target tetrasaccharide scaffold and successful protected-fragment glycosylation chemistry, Despras et al. teach that oxazoline dimer donors are reactive donors that may be coupled with dimer acceptors to form tetrasaccharides, and Santra teaches successful coupling of protected disaccharide fragments to form a protected tetrasaccharide in high yield. Thus, the combined teachings would have suggested preparing the known Colwellia psychrerythraea 34H CPS tetrasaccharide scaffold by reacting disaccharide I-13 with I-18 to obtain tetrasaccharide I-19, with a reasonable expectation that the protected tetrasaccharide product would be formed.
Regarding the protecting groups in I-13 and I-18, the use of different protecting groups would have been obvious to one of ordinary skill in the carbohydrate synthesis because protecting groups are temporary synthetic handles routinely selected to control glycosylation reactivity, stereoselectivity, solubility, and orthogonal deprotection. Vessella et al. demonstrate this ordinary practice by using multiple protecting groups, including benzoyl, benzylidene, TBDPS, NAP, Troc, azide, allyl, and benzyl-type groups, to assemble the Colwellia psychrerythraea 34H CPS tetrasaccharide scaffold. Despras et al. teach that the oxazoline donor strategy is compatible with protected carbohydrate building blocks and that trifluoromethyl oxazoline donors are stable and reactive glycosyl donors. Thus, one of ordinary skill in the art would have understood that the protecting groups used in Vessella et al., Despras et al., and Ramadan et al. are not the inventive feature, but are route-specific temporary groups that may be replaced with other conventional protecting groups compatible with the desired target scaffold.
Claims 12 – 16 are rejected under 35 U.S.C. 103 as being unpatentable over Vessella et al. (Organic & Biomolecular Chemistry, 2019, Vol. 17, Issue 12, page 3129 – 3140, Reference included with PTO-892).
c. Vessella et al. teach a synthesis of the tetrasaccharide repeating unit of the cryoprotectant capsular polysaccharide from Colwellia psychrerythraea 34H (Title). Colwellia psychrerythraea 34H is a psychrophilic Gram-negative bacterium that is able to survive at subzero temperatures by producing a unique capsular polysaccharide (CPS) with anti-freeze properties similar to those of the well-known anti-freeze (glycol)proteins (Abstract). Vessella et al. teach compound 1 (page 3130, Scheme 1):
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which corresponds to the claimed bacterial CPS derivative of formula I, wherein R1’ is an unsubstituted C3 alkoxy; R2’ is -N(H)-R15, wherein R15 is an amino acid residue; R3’ and R4’ are C1 alkanoyl; R5’ – R13’ are hydrogen; and R14’ is OH. Vessella et al. disclose the synthesis of compound 1 (page 3133, Scheme 7):
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,
which show that compound 36 with R2’ = OH is achieved. Thus, Vessella et al. teach the same Colwellia psychrerythraea 34H CPS scaffold as CP-Et recited in claim 14, including the amino sugar residues, uronic acid residues, N-acetyl groups, and threonine amide substituent. Vessella et al. further teach that compound 1 is an artificial O-alkyl glycoside form of the Colwellia psychrerythraea 34H CPS repeating unit rather than the native reducing-end hydroxy form. Specifically, Vessella et al. state that the tetrasaccharide repeating unit of the CPS is synthesized as an O-n-propyl glycoside (Abstract). Vessella et al. also explain that the protected tetrasaccharide is designed with orthogonally cleavable allyl and NAP protecting groups at the pseudo-reducing terminal and the non-reducing end in order to provide future access to repeating unit oligomers (page 3134, Right Col., para. 1). Vessella et al. further compare the deprotected synthetic tetrasaccharide 1 with the natural Colwellia psychrerythraea 34H CPS and report that the only signals showing a remarkable difference included those related to the n-propyl aglycone of 1 (page 3134, Left Col., para. 3). Thus, Vessella et al. teach that the n-propyl aglycone is not part of the native CPS carbohydrate core, but it an artificial terminal aglycone attached to the corresponding Colwellia tetrasaccharide repeating unit.
It would have been prima facie obvious for a person of ordinary skill I the art before the effective filing date of the claimed invention to substitute propoxy of the CPS derivative as taught by Vessella et al. to ethoxy because it has long been established that this type of difference, which is varying the size of a chain, constitutes a form of homology, and is a fact of very close structural similarity, rending the homolog obvious. As was stated in In re Grose, 201 USPZ 57, 63, “The known structural relationship between adjacent homologues, for example, supplies a chemical theory upon which a prima facie case of obviousness of a compound may rest.” See specifically In re Shetty, 195 USPQ 753; In re Wilder, 195 USPQ 426 and Ex Parte Greshem, 121 USPQ 422, all of which feature a compound with a C2 link rejected over a compound with a C1 link. Similarly, In re Chupp, 2 USPQ2d 1437 and In re Coes, 81 USPQ 369 have a compound with a C1 link unpatentable over prior art showing C2 link. Note Ex parte Agouridas, 65 USPQ2d 1142, where a C4 chain was held obvious over a C3 chain. Note also In re Schaub, 190 USPQ 324, 326, where compounds with C5 and C6 chains were called “adjacent homologs in the classic sense”. Ex parte Ruddy, 121 USPQ 427 has a C3 link unpatentable over a C1 link. Ex parte Nathan, 121 USPQ 349 found the insertion of a C2H4 link obvious. In all of these cases, the variation was found to be obvious on the basis of close structural similarity; no secondary teaching was employed. As was stated directly in THE GENERAL TIRE & RUBBER COMPANY v. JEFFERSON CHEMICAL COMPANY, INC., 182 USPQ 70 (1974): “If any structural change is obvious to one skilled in the art, a substitution of the next higher homolog would seem to be.” Note also In re Jones, 21 USPQ2d 1942, which states at 1943 “Particular types or categories of structural similarity without more, have, in past cases, given rise to prima facie obviousness”; one of those listed is “adjacent homologues and structural isomers”. Similar is In re Schechter and LaForge, 98 USPQ 144, 150, which states “a novel useful chemical compound which is homologous or isomeric with compounds of the prior art is unpatentable unless it possesses some unobvious or unexpected beneficial property not possessed by the prior art compounds.” Note also In re Deuel, 34 USPQ2d 1210, 1214 which states, “Structural relationships may provide the requisite motivation or suggestion to modify known compounds to obtain new compounds. For example, a prior art compound may suggest its homologs because homologs often have similar properties and therefore chemists of ordinary skill would ordinarily contemplate making them to try to obtain compounds with improved properties.” Therefore, one of the ordinary skill in the art would have had a reasonable expectation of success to propoxy of the CPS derivative as taught by Vessella et al. to ethoxy because it is known in the art that homologs often have similar properties and the result is predictable.
Regarding claim 14, Vessella et al. teach the same Colwellia psychrerythraea 34H tetrasaccharide scaffold. The compound 1 of Vessella et al. contains a propoxy group at the claimed R1’ position, while CP-Et contains an ethoxy group at that position. Ethoxy and propoxy are adjacent lower alkoxy homologs that differ by one methylene group. The substitution of ethoxy for propoxy at the terminal would have been an obvious homologous modification. Vessella et al. further teach compound 36 in Scheme 7, wherein X is COOH, corresponding to the carboxylic acid form before conversion to the threonine amide. Thus, Vessella et al. teach both the same tetrasaccharide scaffold and the carboxylic acid form relevant to CP-Et. It would have been obvious to retain the carboxylic acid form taught by compound 36 and to use the ethoxy homolog at the R1’ position in place of the propoxy group of compound 1 because these changes represent routine selection of closely related carbohydrate derivatives.
With respect to claim 15, it would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to prepare CP-2 as the corresponding reducing-end hydroxy analog of compound 1 disclosed by Vessella et al. because Vessella et al. teach the same Colwellia psychrerythraea 34H CPS scaffold, including the amino sugar residues, uronic acid residues, N-acetyl groups, and threonine amide substituent. CP-2 differs from compound 1 primarily in that CP-2 contains a hydroxy group at the claimed R1’ position. The hydroxy group represents the conventional reducing-end form of a carbohydrate, and replacement of the terminal propoxy with hydroxy would have been a routine modification that preserves the same biologically relevant Colwellia psychrerythraea 34H CPS core. Therefore, one of ordinary skill would have had a reasonable expectation to prepare CP-2 as the corresponding reducing-end hydroxy analog of compound 1 disclosed by Vessella et al. because CP-2 would have been an obvious close structural variant of compound 1.
Conclusion
No claim is found to be allowable.
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/H.Y.L./Examiner, Art Unit 1693
/SCARLETT Y GOON/Supervisory Patent Examiner, Art Unit 1693
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